Anti-Inflammatory

8-Deoxylactucin suppresses the canonical NF-κB arm, blocking IKKα/β and IκBα phosphorylation and with them the IL-1β, IL-6 and TNF-α transcriptional programme, while inducing NRF2 expression and nuclear translocation, the pairing typical of a thiol-alkylating sesquiterpene lactone ^{8Reference 8Zhou Y et al. · 2025Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2View study →}.

It is the constituent responsible for chicory root extract’s COX-2 protein-expression inhibition, again through NF-κB ^{9Reference 9Cavin C et al. · 2005Inhibition of the expression and activity of cyclooxygenase-2 by chicory extractView study →}, inhibits iNOS at IC₅₀ 6.8 ± 0.1 µM, the most potent of 12 isolates from Cichorium bottae by roughly threefold ^{10Reference 10Elbermawi A et al. · 2024Phytochemical analysis of Cichorium bottae root and anti-inflammatory potential assessment of isolatesView study →}, and was the most active substance for nitric-oxide inhibition in a guaianolide and germacranolide panel on mouse peritoneal cells ^{11Reference 11Harmatha J et al. · 2024Inhibitory effect of selected guaianolide and germacranolide sesquiterpene lactones on nitric oxide productionView study →}.

Most of this is class reactivity: the α-methylene-γ-lactone Michael acceptor is present, and the same study’s structure–activity work found the moiety required across the series ^{8Reference 8Zhou Y et al. · 2025Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2View study →}.

What is compound-specific is that it out-performs its near-identical siblings lactucin and lactucopicrin, which carry the same warhead, across four unrelated laboratories ^{8,12,13,11Reference 8Zhou Y et al. · 2025Sesquiterpene lactones from Cichorium intybus exhibit potent anti-inflammatory and hepatoprotective effects by repression of NF-κB and enhancement of NRF2View study →Reference 12Valente AH et al. · 2021Identification of compounds responsible for the anthelmintic effects of chicory (Cichorium intybus) by molecular networking and bio-guided fractionationView study →Reference 13Foster JG et al. · 2011In vitroIn vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominantly Haemonchus contortus egg populationView study →Reference 11Harmatha J et al. · 2024Inhibitory effect of selected guaianolide and germacranolide sesquiterpene lactones on nitric oxide productionView study →}.

No pharmacokinetics exist in any species, and the class is extensively catabolised by gut bacteria through double-bond hydrogenation, the reaction that destroys the warhead ^{14Reference 14García CJ et al. · 2020In vitroHuman gut microbiota metabolism of dietary sesquiterpene lactones: untargeted metabolomics study of lactucopicrin and lactucin conversion in vitro and in vivoView study →}, so no plasma concentration can be assumed.

The data are isolate data throughout; the one extract-level figure is a supercritical-CO₂ fraction at 53.4% reporter-gene inhibition ^{15Reference 15Baixinho JP et al. · 2021Supercritical CO₂ extraction as a tool to isolate anti-inflammatory sesquiterpene lactones from Cichorium intybus L. rootsView study →}.

Carried by chicory (Cichorium intybus).

Agrimoniin has a human in-vivo result.

An agrimoniin-enriched Potentilla erecta fraction inhibited UVB-induced COX-2 expression in HaCaT keratinocytes, reduced PGE₂ dose-dependently, and inhibited EGF-receptor phosphorylation, the step upstream of UVB-driven COX-2; a placebo-controlled human UV-erythema study then showed dose-dependent inhibition of UVB-induced inflammation, with reduced PGE₂ measured in suction-blister fluid ^{16Reference 16Hoffmann J et al. · 2016In vitroAnti-inflammatory effects of agrimoniin-enriched fractions of Potentilla erecta — in vitro and human UV-erythema studyView study →}.

Fraction potency tracked agrimoniin content across four Sephadex fractions, which is as close to attribution as a fraction study can come.

At the enzyme level the isolate is potent: human neutrophil elastase IC₅₀ 0.9 µM, with docking suggesting unspecific binding ^{17Reference 17Hrenn A et al. · 2006In vitroPlant phenolics inhibit neutrophil elastase — in vitroView study →}, hyaluronidase IC₅₀ 2.65 µM, lipoxidase IC₅₀ 36.5 µM and H₂O₂ scavenging SC₅₀ 0.20 µM ^{18Reference 18Bazylko A et al. · 2013In vitroIn vitro antioxidant and anti-inflammatory activities of extracts from Potentilla recta and its main ellagitannin, agrimoniinView study →}.

The human result was topical, which sidesteps absorption rather than solving it; for oral ellagitannin material the anti-inflammatory activity travels with the urolithin metabolites rather than the parent tannin ^{19Reference 19Piwowarski JP et al. · 2014Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — ex vivoView study →}.

The best-specified anti-inflammatory mechanism of carnosic acid is inhibition of microsomal prostaglandin E₂ synthase-1, the terminal enzyme that makes PGE₂ downstream of COX: IC₅₀ 5.0 µM cell-free and 9.3 µM in a human whole-blood assay after LPS stimulation, with 6-keto-PGF₁α, 12-HHT and thromboxane B₂ unaffected and no inhibition of COX-1 or COX-2 ^{20Reference 20Bauer J et al. · 2012Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1 — human whole-blood assayView study →}.

Sparing the other prostanoids is what the NSAIDs fail to do, and it is the profile drug programmes have pursued for two decades.

Carnosol was active cell-free but not in whole blood ^{20Reference 20Bauer J et al. · 2012Carnosol and carnosic acids from Salvia officinalis inhibit microsomal prostaglandin E2 synthase-1 — human whole-blood assayView study →}, a clean molecule-level separation.

Downstream of that, isolated carnosic acid suppressed P2X7R–NLRP3 inflammasome activation, IL-1β and HMGB1 release and neutrophil-extracellular-trap formation in a mouse chronic-ethanol-plus-binge liver model ^{21Reference 21Zuo RM et al. · 2023AnimalCarnosic acid suppressed the formation of NETs in alcoholic hepatosteatosis based on the P2X7R–NLRP3 axis — miceView study →}, and it inhibits LPS-driven microglial activation in the pro-electrophilic mode ^{22Reference 22Yanagitai M et al. · 2012In vitroCarnosic acid, a pro-electrophilic compound, inhibits LPS-induced activation of microglia — in vitroView study →}.

The whole-blood result is ex vivo on donor blood, not oral dosing.

Carnosol’s best-replicated action has two mechanisms pinned down rather than inferred.

It suppresses NF-κB across unrelated cell types, in LPS-stimulated cardiomyoblasts, activated microglia, RANKL-driven osteoclasts and collagen-induced arthritic joints, where 40 mg/kg/day cut swelling, arthritis index and serum IL-6, MCP-1 and TNF-α and blocked the TLR4/NF-κB/MAPK axis ^{23,24Reference 23Li L et al. · 2021Rosmanol and carnosol synergistically alleviate rheumatoid arthritis through inhibiting TLR4/NF-κB/MAPK pathwayView study →Reference 24Li X et al. · 2018Carnosol modulates Th17 cell differentiation and microglial switch in experimental autoimmune encephalomyelitisView study →}.

Beyond that generic readout, carnosol binds p38 MAPK directly and blocks its activation in angiotensin-II-driven cardiac remodelling ^{25Reference 25Xu D et al. · 2024Carnosol attenuates angiotensin II-induced cardiac remodeling and inflammation via directly binding to p38 and inhibiting p38 activationView study →}, and it acts as a direct or partial PPAR-γ agonist on the mPGES-1/PPAR-γ axis, which the authors credit for its greater anti-inflammatory effect than carnosic acid in zymosan-induced chronic inflammation ^{26Reference 26Gazzillo E et al. · 2025AnimalCarnosol modulates mPGES-1/PPAR-γ biological axis — from in silico to in vivo clinical imaging and investigationsView study →}.

That receptor mechanism is the strongest single argument that carnosol’s activity is its own.

In human monocyte-derived macrophages carnosol and carnosic acid together cut leukotriene and prostaglandin formation while activating 15-LOX to raise specialised pro-resolving mediators, a lipid-mediator class switch ^{27Reference 27Nischang V et al. · 2026Carnosic acid and carnosol promote lipid mediator class-switching toward inflammation resolution in human macrophagesView study →}; the finding is shared between the two molecules.

The nearest human data is a randomised double-blind placebo-controlled UV-erythema trial in 40 volunteers where a 2% sage extract rich in phenolic diterpenes matched 1% hydrocortisone ^{28Reference 28Reuter J et al. · 2007RCTSage extract rich in phenolic diterpenes inhibits ultraviolet-induced erythema in vivo — a randomised double-blind placebo-controlled clinical trialView study →}, an extract rather than the molecule.

Casuarinin was isolated from Melastoma malabathricum root by bioactivity-guided fractionation as the plant’s most potent selective neutrophil elastase inhibitor (IC₅₀ 2.79 ± 0.07 µM), then given orally to C57BL/6 mice at 50 and 100 mg/kg/day against 5-fluorouracil-induced intestinal mucositis.

At 100 mg/kg/day it reduced body-weight loss, restored intestinal crypt proliferation, suppressed inflammation and barrier dysfunction, and reversed 5-FU-driven microbiota dysbiosis, including the Firmicutes:Bacteroidetes ratio and Lactobacillus murinus and Candidatus Arthromitus abundance ^{40Reference 40Chen KJ et al. · 2022AnimalProtective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis — impact on inflammation and gut microbiota dysbiosisView study →}.

Casuarinin also cut IL-8 production in HT-29 colon epithelial cells ^{41Reference 41Yang GX et al. · 2014Chemical constituents from Melastoma dodecandrum and their inhibitory activity on interleukin-8 production in HT-29 cellsView study →}.

The action is luminal, shown for the isolate, and unreplicated.

Carried by raspberry leaf and arjuna.

Cryptotanshinone inhibits NLRP3 inflammasome activation in macrophages while leaving the AIM2 and NLRC4 inflammasomes untouched; the negative controls are what make the result credible, since a redox-active quinone that suppressed all three would be a much weaker finding.

It acts upstream, blocking Ca²⁺ signalling and mitochondrial ROS induction, and in vivo it reduces caspase-1 activation and IL-1β secretion in mouse endotoxemia and in methionine/choline-deficient-diet NASH ^{54Reference 54Liu H et al. · 2021In vitroCryptotanshinone specifically suppresses NLRP3 inflammasome activation and protects against inflammasome-mediated diseases — in vitro and mouse in vivo studyView study →}.

Around that sits a consistent rodent disease set: DSS colitis, where it suppresses STAT3 activation and Th17 differentiation in both acute and chronic disease ^{55Reference 55Fan LM et al. · 2022AnimalCryptotanshinone ameliorates dextran sulfate sodium-induced murine acute and chronic ulcerative colitis via suppressing STAT3 activation and Th17 cell differentiation — mouse in vivo studyView study →}; LPS-plus-cigarette-smoke COPD through the Keap1/Nrf2 axis ^{56Reference 56Song H et al. · 2023AnimalCryptotanshinone alleviates lipopolysaccharide and cigarette smoke-induced chronic obstructive pulmonary disease in mice via the Keap1/Nrf2 axis — mouse in vivo studyView study →}; and asthmatic airway remodelling through TWEAK–TGF-β1 crosstalk ^{57Reference 57Wang C et al. · 2019AnimalCryptotanshinone attenuates airway remodeling by inhibiting crosstalk between tumor necrosis factor-like weak inducer of apoptosis and transforming growth factor beta 1 signaling pathways in asthma — mouse in vivo studyView study →}.

The purified lipophilic danshen fraction containing cryptotanshinone and dihydrotanshinone I is anti-inflammatory in cell and animal models ^{58Reference 58Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone, and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}.

Carried by dan shen.

Curcumin is the most-studied plant anti-inflammatory at the molecular level and acts on the pathway at three points at once.

It inhibits NF-κB, the master transcription factor of the inflammatory programme, and it is a dual inhibitor of arachidonic-acid metabolism, down-regulating both COX-2 and 5-LOX where the NSAIDs act on one arm.

The human signal is real where the pathway is reachable: a meta-analysis of randomised trials found curcumin extracts reduced arthritis pain and function scores, and a multicentre trial found a standardised extract as effective as ibuprofen for knee osteoarthritis with fewer gastrointestinal complaints.

Absorption is the limit rather than mechanism.

Free curcumin is poorly absorbed, rapidly conjugated and unstable at intestinal pH, so nearly every positive trial used a bioavailability-enhanced preparation with piperine or a phospholipid or nanoparticle carrier.

Curcumin is also a PAINS compound, an assay-promiscuous scaffold, which is part of why in-vitro potency has translated unevenly.

Carried by turmeric.

Helenalin is the compound on which the sesquiterpene-lactone anti-inflammatory mechanism was established, and it remains the class’s cleanest structure–function result.

It alkylates cysteine 38 in the DNA-binding domain of the p65/RelA subunit of NF-κB, physically preventing the transcription factor from binding DNA ^{105,106Reference 105Lyss G et al. · 1998In vitroThe anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65 — in vitroView study →Reference 106García-Piñeres AJ et al. · 2001In vitroCysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones — in vitroView study →}.

The selectivity is documented: it blocks NF-κB while leaving Oct-1, TBP, Sp1 and STAT5 untouched at 1–20 µM ^{107Reference 107Lyss G et al. · 1997In vitroHelenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB — in vitroView study →}.

The mechanism arrived by correction, the 1997 IκB-complex model being superseded by direct p65 targeting in 1998 and pinned to the residue by mutagenesis in 2001 ^{107,105,106Reference 107Lyss G et al. · 1997In vitroHelenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB — in vitroView study →Reference 105Lyss G et al. · 1998In vitroThe anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65 — in vitroView study →Reference 106García-Piñeres AJ et al. · 2001In vitroCysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones — in vitroView study →}.

In whole arnica preparations, NF-κB/NF-AT inhibition and reduced IL-1/TNF-α release correlate with sesquiterpene-lactone content and ester pattern, and the same preparations reduce croton-oil ear oedema in mice, with methacrylate and tiglinate esters out-performing the acetate ^{108Reference 108Klaas CA et al. · 2002In vitroStudies on the anti-inflammatory activity of phytopharmaceuticals prepared from Arnica flowers — in vitro and animal model (mouse ear oedema)View study →}.

The mechanism is a class property: across 103 sesquiterpene lactones, NF-κB activity tracks the number of alkylating structural elements rather than the skeleton ^{109Reference 109Siedle B et al. · 2004In vitroQuantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kappaB — in vitroView study →}, so what is helenalin-specific is the named residue and the potency (1–20 µM against about 200 µM for 11α,13-dihydrohelenalin ^{107Reference 107Lyss G et al. · 1997In vitroHelenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB — in vitroView study →}).

The route is topical only.

Helenalin esters cross the stratum corneum from tinctures and gels ^{110Reference 110Wagner S et al. · 2004In vitroSkin penetration studies of Arnica preparations and of their sesquiterpene lactones — in vitroView study →}, and the intact skin barrier prevents the same reactive chemistry from becoming systemic poisoning ^{111,112Reference 111Chapman DE et al. · 1988AnimalAcute toxicity of helenalin in BDF1 mice — animal modelView study →Reference 112Witzel DA et al. · 1976AnimalMammalian toxicity of helenalin, the toxic principle of Helenium microcephalum DC (smallhead sneezeweed) — animal model, five speciesView study →}.

Carried by arnica.

Parthenolide is the reference covalent NF-κB inhibitor of the plant kingdom, and its target residues are named: it alkylates cysteine-179 of IKKβ, blocking the IκB kinase step ^{136Reference 136Kwok BH et al. · 2001In vitroThe anti-inflammatory natural product parthenolide from the medicinal herb feverfew directly binds to and inhibits IκB kinase — in vitroView study →}, and cysteine-38 in the p65 DNA-binding loop, blocking NF-κB’s contact with DNA directly ^{106,137Reference 106García-Piñeres AJ et al. · 2001In vitroCysteine 38 in p65/NF-kappaB plays a crucial role in DNA binding inhibition by sesquiterpene lactones — in vitroView study →Reference 137García-Piñeres AJ et al. · 2004In vitroRole of cysteine residues of p65/NF-κB on the inhibition by the sesquiterpene lactone parthenolide and N-ethyl maleimide, and on its transactivating potential — in vitroView study →}; a third group found it disables activation of the IKK complex without inhibiting IKKα, IKKβ or MEKK1 in their system ^{138Reference 138Hehner SP et al. · 1999In vitroThe antiinflammatory sesquiterpene lactone parthenolide inhibits NF-κB by targeting the IκB kinase complex — in vitroView study →}.

The reaction is a Michael addition of an accessible thiol onto the α-methylene-γ-lactone, and the cleanest proof is in vivo: isolated parthenolide at 20 mg/kg i.p. blocked hyperalgesia and oedema in the rat carrageenan model, while 11,13-dihydroparthenolide, the identical molecule with that methylene saturated, did nothing ^{139Reference 139Feltenstein MW et al. · 2004AnimalAnti-inflammatory and anti-hyperalgesic effects of sesquiterpene lactones from Magnolia and Bear’s foot — animal modelView study →}.

Oral parthenolide up to 4 mg/day in humans is undetectable in plasma (limit of detection 0.5 ng/mL), so no in-vitro potency translates to a systemic human effect ^{140Reference 140Curry EA 3rd et al. · 2004Clinical trialPhase I dose escalation trial of feverfew with standardized doses of parthenolide in patients with cancer — clinical trialView study →}.

NF-κB inhibition is a shared property of the sesquiterpene lactone class, scaling with the number of reactive centres a molecule carries rather than its identity ^{125,141Reference 125Rüngeler P et al. · 1999In vitroInhibition of transcription factor NF-kappaB by sesquiterpene lactones: a proposed molecular mechanism of action — in vitroView study →Reference 141Umemura K et al. · 2008In vitroPreconditioning by sesquiterpene lactone enhances H2O2-induced Nrf2/ARE activation — in vitroView study →}, and costunolide out-performed parthenolide head-to-head on the same assay ^{50Reference 50Koo TH et al. · 2001In vitroA sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa B phosphorylation — in vitroView study →}.

Parthenolide is the class exemplar rather than a uniquely potent agent.

Carried by feverfew.

Rosmanol has both a detailed cell mechanism and an independent animal model.

In LPS-stimulated RAW 264.7 macrophages it markedly inhibited iNOS and COX-2 at protein and gene level, with NO and PGE₂ falling accordingly.

The upstream picture is unusually complete for a plant phenolic: rosmanol prevented IκB degradation and phosphorylation and blocked NF-κB translocation, inhibited STAT3 phosphorylation and translocation, suppressed C/EBPβ and C/EBPδ protein expression, and blocked LPS-induced phosphorylation of ERK1/2, p38 MAPK and PI3K/Akt ^{153Reference 153Lai CS et al. · 2009In vitroRosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-κB, STAT3 and C/EBP signaling pathways — in vitroView study →}.

Four transcription-factor and kinase arms of one pathway were measured rather than inferred, and the authors concluded that rosmanol might contribute to the anti-inflammatory effect of rosemary.

In vivo, rosmanol and carnosol were isolated from Callicarpa longissima, a Yao folk arthritis medicine, and tested in type-II collagen-induced arthritis in DBA/1 mice.

Each alone at 40 mg/kg/day reduced swelling, redness, synovitis and arthritis index and lowered serum IL-6, MCP-1 and TNF-α, blocking activation of the TLR4/NF-κB/JNK/p38 axis; in combination at 20 mg/kg/day each, both the anti-arthritic effect and the pathway inhibition were significantly greater than either compound alone ^{23Reference 23Li L et al. · 2021Rosmanol and carnosol synergistically alleviate rheumatoid arthritis through inhibiting TLR4/NF-κB/MAPK pathwayView study →}.

That synergy arm shows rosmanol contributes something carnosol does not fully duplicate, which in-vitro co-occurrence data can never show.

It is one animal model from one laboratory, unreplicated, with no dose–response below 20 mg/kg and no plasma measurement in the efficacy study.

The macrophage work is at 20–50 µM, well above the 1.8 µM exposure ceiling ^{154,155Reference 154Wang L et al. · 2017AnimalDetermination and pharmacokinetic study of three diterpenes in rat plasma by UHPLC-ESI-MS/MS after oral administration of Rosmarinus officinalis L. extract — ratsView study →Reference 155Romo Vaquero M et al. · 2013AnimalBioavailability of the major bioactive diterpenoids in a rosemary extract — metabolic profile in the intestine, liver, plasma and brain of Zucker ratsView study →}.

Sarsasapogenin blocks the inflammatory cascade at its entry point.

It inhibits LPS binding to TLR4 and suppresses the downstream IRAK1/TAK1/IκBα phosphorylation that drives NF-κB and MAPK activation, while shifting macrophages from an M1 to an M2 phenotype and restoring Th17/Treg balance ^{171Reference 171Lim SM et al. · 2015AnimalTimosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting NF-κB and MAPK activation and restoring Th17/Treg cell balanceView study →}.

It also suppresses NLRP3 and NLRP1 inflammasome assembly and the caspase-1-mediated maturation of IL-1β and IL-18 ^{172,173,174Reference 172Kong L et al. · 2021Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptorView study →Reference 173Choi YH · 2023Reduction of high glucose-induced oxidative injury in human retinal pigment epithelial cells by sarsasapogenin through inhibition of ROS generation and inactivation of NF-κB/NLRP3 inflammasome pathwayView study →Reference 174Yuan Q et al. · 2026Sarsasapogenin attenuates renal ischemia-reperfusion injury by inhibiting the NF-κB pathway and NLRP3 inflammasome-mediated pyroptosisView study →}.

The effect is replicated across colitis, asthma, dermatitis and adipose-inflammation models ^{175,176Reference 175Mustafa NH et al. · 2022Chemistry, biosynthesis and pharmacology of sarsasapogenin: a potential natural steroid molecule for new drug design, development and therapyView study →Reference 176Mandlik DS et al. · 2021AnimalProtective effect of sarsasapogenin in TNBS induced ulcerative colitis in rats associated with downregulation of pro-inflammatory mediators and oxidative stressView study →}, and the aglycone out-performed its own parent glycoside timosaponin A-III both in vitro and in vivo, the strongest evidence in this compound class that the sapogenin is the active species ^{171Reference 171Lim SM et al. · 2015AnimalTimosaponin AIII and its metabolite sarsasapogenin ameliorate colitis in mice by inhibiting NF-κB and MAPK activation and restoring Th17/Treg cell balanceView study →}.

There are no human data, and several of the disease models co-dose fluticasone at half strength, which confounds attribution ^{175Reference 175Mustafa NH et al. · 2022Chemistry, biosynthesis and pharmacology of sarsasapogenin: a potential natural steroid molecule for new drug design, development and therapyView study →}.

Carried by sarsaparilla and shatavari.

Tanshinone I’s mechanism is unusually upstream.

A 2002 activity-guided isolation from 300 plant extracts landed on it as the active principle of the S. miltiorrhiza ethyl-acetate subfraction: it inhibited PGE₂ formation from LPS-stimulated RAW 264.7 macrophages at IC₅₀ 38 µM but did not affect COX-2 activity or expression, instead inhibiting type IIA human recombinant secretory PLA₂ at IC₅₀ 11 µM and rabbit recombinant cPLA₂ at IC₅₀ 82 µM, throttling arachidonate release rather than its conversion.

It was active in rat carrageenan paw oedema and adjuvant-induced arthritis in vivo ^{178Reference 178Kim SY et al. · 2002AnimalEffects of tanshinone I isolated from Salvia miltiorrhiza Bunge on arachidonic acid metabolism and in vivo inflammatory responsesView study →}.

Two decades later a second mechanism was identified: tanshinone I is a specific NLRP3 inflammasome inhibitor, blocking NLRP3 but leaving AIM2 and NLRC4 untouched, and it does so by disrupting the NLRP3–ASC association, preventing assembly; it was protective in mouse LPS septic shock and NASH ^{179Reference 179Zhao J et al. · 2023Tanshinone I specifically suppresses NLRP3 inflammasome activation by disrupting the association of NLRP3 and ASCView study →}.

A third strand is microglial and equally selective: in LPS-stimulated BV-2 microglia it suppressed NO, TNF-α, IL-1β and IL-6 and blocked NF-κB p65 nuclear translocation and DNA binding without suppressing the M2 markers IL-10 and IL-1Ra ^{180Reference 180Wang S et al. · 2015AnimalTanshinone I selectively suppresses pro-inflammatory genes expression in activated microglia and prevents nigrostriatal dopaminergic neurodegeneration in a mouse model of Parkinson’s diseaseView study →}, and the effect extended to a psoriasis-like dermatitis model with effects on keratinocyte differentiation ^{181Reference 181Wang Q et al. · 2025Tanshinone I ameliorates psoriasis-like dermatitis by suppressing inflammation and regulating keratinocyte differentiationView study →}.

Anti-adhesion is part of the same action: it dose-dependently suppressed ICAM-1 and VCAM-1 in TNF-α-stimulated HUVECs, reducing monocyte adhesion, an effect reproduced by ICAM-1/VCAM-1 siRNA ^{182Reference 182Nizamutdinova IT et al. · 2008Tanshinone I suppresses growth and invasion of human breast cancer cells, MDA-MB-231, through regulation of adhesion moleculesView study →}.

Every enzyme IC₅₀ (11–82 µM) is far above plausible plasma exposure from an oral preparation, and the total tanshinone fraction out-performed the molecule alone in vitro ^{58Reference 58Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone, and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}.

Tanshinone IIA’s anti-inflammatory action runs through downregulation of TLR/NF-κB and MAPK/NF-κB signalling, with reduced TNF-α, IL-6 and IL-1β downstream, reported consistently across cell and animal models ^{183Reference 183Guo R et al. · 2020ReviewPharmacological activity and mechanism of tanshinone IIA in related diseases — reviewView study →}.

It is an electrophilic ortho-quinone, which is the structural basis for both this activity and its Nrf2 induction; the two are mechanistically coupled.

A study that purified all four major tanshinones from S. miltiorrhiza and tested them side by side found anti-inflammatory activity across the lipophilic fraction, with cryptotanshinone and dihydrotanshinone I the more potent members on the antibacterial endpoint ^{58Reference 58Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone, and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}, so this is a fraction-level property in which tanshinone IIA participates rather than one it owns.

The human data belong to the extract.

A meta-analysis of 28 RCTs and 2,969 participants found the Chinese Tanshinone capsule, a multi-tanshinone preparation, cut acne recurrence (RR 0.44, 95% CI 0.34–0.57) and lowered TNF-α, IL-4, IL-6 and IL-8, at GRADE very low to moderate certainty ^{184Reference 184Deng Y et al. · 2025Meta-analysisEfficacy and safety of Tanshinone capsule in acne vulgaris — systematic review and meta-analysis of 28 randomised controlled trialsView study →}.

The separate 4,654-patient inflammatory-marker dataset, with IL-6, TNF-α, IL-1β, ICAM-1, MCP-1 and fractalkine all lowered, is sodium tanshinone IIA sulfonate given by injection ^{185Reference 185Xie F et al. · 2025Meta-analysisEffects of sodium tanshinone IIA sulfonate injection on pro-inflammatory cytokines, adhesion molecules and chemokines in Chinese patients with atherosclerosis and atherosclerotic cardiovascular disease — meta-analysis of 42 randomised controlled trialsView study →}, a different molecule by a different route.

No trial has tested the isolated compound in an inflammatory condition, and the acne result cannot be apportioned between the tanshinones in the capsule.

Tussilagone’s anti-inflammatory activity is isolate work throughout.

It induces heme oxygenase-1 in murine macrophages, suppressing NO, TNF-α and PGE₂ ^{194Reference 194Hwangbo C et al. · 2009In vitroThe anti-inflammatory effect of tussilagone, from Tussilago farfara, is mediated by the induction of heme oxygenase-1 in murine macrophages — in vitroView study →}; in LPS-activated BV-2 microglia it inhibits NO and PGE₂ with IC₅₀ 8.67 µM and 14.1 µM, suppressing iNOS and COX-2 protein and mRNA through blocked IκBα degradation and p65 nuclear translocation ^{195Reference 195Lim HJ et al. · 2008In vitroSuppression of inducible nitric oxide synthase and cyclooxygenase-2 expression by tussilagone from Farfarae flos in BV-2 microglial cells — in vitroView study →}; it suppresses dendritic-cell function through HO-1 ^{196Reference 196Park Y et al. · 2014In vitroTussilagone inhibits dendritic cell functions via induction of heme oxygenase-1 — in vitroView study →} and ameliorates DSS colitis in mice ^{197Reference 197Cheon HJ et al. · 2018AnimalTussilagone, a major active component in Tussilago farfara, ameliorates inflammatory responses in dextran sulphate sodium-induced murine colitis — mouse in vivoView study →}.

A 2026 COPD study supplies the target: biotin-labelled tussilagone pulls down KEAP1 and covalently modifies Cys434, a previously unreported high-reactivity cysteine in the Kelch domain, activating Nrf2 and thereby damping NF-κB and NLRP3 ^{198Reference 198Xu LT et al. · 2026AnimalTussilagone attenuated cigarette smoke-induced chronic obstructive pulmonary disease through regulating Nrf2 and NF-κB/NLRP3 inflammasome via directly targeting cysteine 434 of KEAP1 — mouse in vivoView study →}.

The molecule has no α-methylene-γ-lactone, so the usual sesquiterpene-lactone explanation for thiol trapping does not apply and the reactive carbon is unassigned.

The evidence is in vitro and mouse only, with no human anti-inflammatory data, and the effective 5–20 µM range has never been reconciled with about 1.3% oral bioavailability in rats ^{199Reference 199Liu YF et al. · 2008AnimalDetermination and pharmacokinetic study of tussilagone in rat plasma by RP-HPLC method — rat pharmacokineticsView study →}.

Carried by coltsfoot.

Urolithin A carries the systemic anti-inflammatory activity of the whole hydrolysable-tannin class, because the parent tannins never leave the gut lumen.

It blocks NF-κB p65 nuclear translocation and p50 DNA binding, cutting iNOS, TNF-α, IL-1β and IL-6 in LPS-stimulated macrophages; the authors were explicit that the active range (≥40 µM) is physiologically relevant for gut tissue rather than blood ^{200Reference 200Piwowarski JP et al. · 2015AnimalUrolithins, gut microbiota-derived metabolites of ellagitannins, inhibit LPS-induced inflammation in RAW 264.7 murine macrophages — active at ≥40 µMView study →}.

It is also a direct aryl hydrocarbon receptor (AhR) ligand and selective antagonist, and AhR is required for its suppression of IL-6 and PTGS2 in intestinal epithelial cells ^{201Reference 201Muku GE et al. · 2018Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonistView study →}.

The one low-concentration result is on human neutrophils: 1 µM urolithin A cut fMLP- and PMA-stimulated ROS release by 42.6% and 53.7% ^{202Reference 202Piwowarski JP et al. · 2014Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µMView study →}.

Orally it suppresses carrageenan paw oedema in rats ^{95Reference 95Ishimoto H et al. · 2011AnimalIn vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin AView study →}, and in humans C-reactive protein falls in three randomised trials at 500–1,000 mg/day ^{203,204,205Reference 203Singh A et al. · 2022RCTUrolithin A improves muscle strength, exercise performance and biomarkers of mitochondrial health in a randomized trial in middle-aged adults (NCT03464500) — primary endpoint peak power output not metView study →Reference 204Liu S et al. · 2022RCTEffect of urolithin A supplementation on muscle endurance and mitochondrial health in older adults — a randomized clinical trial (NCT03283462); co-primary endpoints not metView study →Reference 205Zhao H et al. · 2024RCTAssessment of urolithin A effects on muscle endurance, strength, inflammation, oxidative stress and protein metabolism in male athletes with resistance training — an 8-week randomized, double-blind, placebo-controlled study (n = 20)View study →}, with an independent systematic review describing the anti-inflammatory effect as dose-dependent ^{206Reference 206Kuerec AH et al. · 2024Systematic reviewTargeting aging with urolithin A in humans — a systematic review (5 studies, 250 participants)View study →}.

Circulating urolithin A is overwhelmingly the glucuronide, which dramatically hampers its activity ^{207Reference 207Ávila-Gálvez MÁ et al. · 2019Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammationView study →}; the escape route is local deconjugation at inflamed tissue ^{207Reference 207Ávila-Gálvez MÁ et al. · 2019Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammationView study →}, and PBPK modelling argues most in-vitro effect concentrations are unreachable systemically ^{208Reference 208Aichinger G et al. · 2023Physiologically-based pharmacokinetic modeling of the postbiotic supplement urolithin A predicts its bioavailability is orders of magnitude lower than concentrations that induce toxicity, but also neuroprotective effectsView study →}.

CRP is a biomarker rather than an outcome.

11β,13-Dihydrolactucin inverts the class pattern that governs the other sesquiterpene lactones.

Most of them act on NF-κB because their α-methylene-γ-lactone alkylates cysteine thiols, a class property that says nothing about any individual member.

11β,13-Dihydrolactucin has that group reduced away, and in a six-lactone comparison no cysteine adducts formed for it, while they did for lactucin, lactucopicrin, parthenolide and costunolide ^{1Reference 1Matos MS et al. · 2020In vitroAssessing the intestinal permeability and anti-inflammatory potential of sesquiterpene lactones from chicory — in vitroView study →}.

It was nevertheless the most anti-inflammatory of the six, inhibiting the calcineurin/NFAT-responsive reporter Crz1 by 43 ± 8% at 12.5 µM and about 54% at 3.6 µM, against 18–20% for the others ^{1Reference 1Matos MS et al. · 2020In vitroAssessing the intestinal permeability and anti-inflammatory potential of sesquiterpene lactones from chicory — in vitroView study →}; the proposed reason is that, not consumed by thiol adduction, it stays available to reach its targets.

A follow-up ran it through three intestinal models: in a Caco-2/HT29-MTX-E12/Raji B triple co-culture it prevented NF-κB and MAPK p38 activation, cut IL-8 release, and reduced IL-6 and TNF-α gene expression plus iNOS and COX-2 gene and protein expression; in a myofibroblast-like human model it lowered TNF-α and PGE₂; and in a zebrafish gut-inflammation model it reduced neutrophil infiltration ^{2Reference 2Matos MS et al. · 2024AnimalUnveiling the anti-inflammatory potential of 11β,13-dihydrolactucin for application in inflammatory bowel disease management — cell models and zebrafish animal modelView study →}.

There is no mammalian in-vivo colitis model, no oral dosing study and no named binding partner; NF-κB and p38 are readouts rather than demonstrated targets.

With only about 7% of an ingested chicory lactone dose reaching blood ^{3Reference 3Weng H et al. · 2020Clinical trialLow oral bioavailability and partial gut microbiotic and phase II metabolism of Brussels/witloof chicory sesquiterpene lactones — human volunteersView study →}, the distance between these micromolar concentrations and an achievable gut-luminal or systemic exposure is unquantified.

Carried by chicory (Cichorium intybus, the vehicle for all of this work), dandelion root ^{4Reference 4Kisiel W · 2000Further sesquiterpenoids and phenolics from Taraxacum officinaleView study →}, wild lettuce ^{5Reference 5Wesołowska A et al. · 2006AnimalAnalgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice — animal in vivoView study →}, garden lettuce and radicchio ^{6,7Reference 6Lang R et al. · 2022In vitroOverlapping activation pattern of bitter taste receptors affect sensory adaptation and food perception — in vitro receptor assays plus human sensory panelView study →Reference 7Mai F · 2016Structural and sensory characterization of novel sesquiterpene lactones from iceberg lettuceView study →}.

β-Caryophyllene is the one common dietary terpene with a cannabinoid action: it is a selective functional agonist at the CB2 receptor (Ki ≈ 155 nM) with negligible CB1 binding, so it engages the endocannabinoid system’s immune arm without psychoactivity ^{29Reference 29Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

The evidence for causality is clean.

Oral β-caryophyllene reduced inflammatory paw oedema in normal mice but not in CB2-knockout mice, which pins the effect to the receptor rather than to generic terpene activity ^{29Reference 29Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

CB2 sits on immune cells, so this is a target-anchored route distinct from the COX/LOX and NF-κB mechanisms that dominate the rest of the class.

There are no human anti-inflammatory trials, and dietary intake sits far below the doses used ^{29Reference 29Gertsch J et al. · 2008In vitroBeta-caryophyllene is a dietary cannabinoid — in vitro receptor pharmacology + in-vivo mouse modelView study →}.

Carried by black pepper, clove, cannabis, copaiba and rosemary.

Castalagin suppresses NF-κB, demonstrated for the isolated molecule in two infection-driven epithelial models: gastric epithelium, where IL-8 fell, and keratinocytes, where cytokine release fell ^{30,31Reference 30Piazza S et al. · 2023Ellagitannins from Castanea sativa Mill. leaf extracts impair H. pylori viability and infection-induced inflammation in human gastric epithelial cellsView study →Reference 31Piazza S et al. · 2024Investigation into the anti-acne effects of Castanea sativa Mill leaf and its pure ellagitannin castalagin in HaCaT cells infected with Cutibacterium acnesView study →}.

A chestnut-wood extract carrying the same ellagitannins shows a dual PPARγ-activating and NF-κB-suppressing signature in intestinal inflammation, though there the tested article is the extract rather than the molecule ^{32Reference 32Lambert D et al. · 2026Turning off inflammation naturally via dual antioxidant and anti-inflammatory actions of chestnut wood extract through PPARγ and NF-κB pathwaysView study →}.

Every result is in vitro at micromolar concentrations that an unabsorbed tannin reaches only at a mucosal surface or in the gut lumen, so the action is local rather than systemic.

Carried by camu-camu.

Casuarictin’s anti-inflammatory activity has been reproduced by four unrelated laboratories in four systems.

In LPS/IFN-γ-activated RAW264.7 macrophages the purified compound suppressed nitric oxide production at ID₅₀ 2.0–5.1 µM and reduced iNOS protein induction, with potency falling to about 30–130 µM against already-activated cells ^{33Reference 33Ishii R et al. · 1999In vitroInhibitory effects of hydrolyzable tannins from Melastoma dodecandrum Lour. on nitric oxide production by RAW264.7 macrophages — in vitroView study →}.

In human gastric epithelium, casuarictin tested as an isolate behaved as a clean NF-κB inhibitor of IL-8 release, distinguishable in the same experiment from agrimoniin, which acted on IL-8 through NF-κB and other targets ^{34Reference 34Fumagalli M et al. · 2016In vitroStrawberry tannins inhibit IL-8 secretion in a cell model of gastric inflammation — in vitroView study →}; the follow-up extended this to IL-6 and IL-8 suppression in Helicobacter pylori-infected GES-1 cells ^{35Reference 35Martinelli G et al. · 2025In vitroInvestigating ellagitannins from strawberry (Fragaria × ananassa Duch.) as a new strategy to counteract H. pylori infection and inflammation — in vitroView study →}.

In normal human epidermal keratinocytes, purified casuarictin inhibited poly(I:C)-induced IL-8 mRNA and protein in a TLR-3 model of UV damage, and the authors concluded it and strictinin accounted for the Rosa roxburghii extract’s activity ^{36Reference 36Takayama S et al. · 2021In vitroEllagitannins from Rosa roxburghii suppress poly(I:C)-induced IL-8 production in human keratinocytes — in vitroView study →}.

Casuarictin purified to 94% from sea buckthorn leaf strongly inhibited LPS-induced TNF-α synthesis in human whole blood ex vivo ^{37Reference 37Sokolova E et al. · 2025In vitroInhibitory potential of sea buckthorn leaves extracts and its component casuarictin on pancreatic enzymes and LPS-induced TNF-α synthesis in human whole blood — in vitro / ex vivoView study →}, the closest this literature comes to a human system.

Low micromolar concentrations are reachable at a gut or skin surface and not in plasma ^{38,39Reference 38Piwowarski JP et al. · 2016Differences in metabolism of ellagitannins by human gut microbiota ex vivo culturesView study →Reference 39Daniel EM et al. · 1991In vitroThe effects of pH and rat intestinal contents on the liberation of ellagic acid from purified and crude ellagitannins — in vitroView study →}.

Carried by clove, guava and raspberry leaf.

Chelidonine suppresses the TLR4/NF-κB arm of innate inflammatory signalling.

It blocks IκBα degradation and p65 nuclear translocation, downregulates TLR4 itself, and reduces iNOS, COX-2, NO, PGE2, TNF-α and IL-6 in macrophages and in LPS-challenged mice ^{42Reference 42Liao W et al. · 2018In vitroChelidonine suppresses LPS-induced production of inflammatory mediators through inhibition of the TLR4/NF-κB signaling pathway in RAW264.7 macrophages — in vitro/animalView study →}.

A second axis appears in allergic inflammation, with suppression of eotaxin-2, IL-4, IL-13 and IL-17 through STAT6 downregulation and Foxp3 upregulation in asthmatic mice ^{43Reference 43Kim SH et al. · 2015AnimalChelidonine, a principal isoquinoline alkaloid of Chelidonium majus, attenuates eosinophilic airway inflammation by suppressing IL-4 and eotaxin-2 expression in asthmatic mice — animalView study →}, and the same NF-κB mechanism attenuates chondrocyte catabolism and cartilage degradation in a rat osteoarthritis model ^{44Reference 44Li M et al. · 2023AnimalChelidonine reduces IL-1β-induced inflammation and matrix catabolism in chondrocytes and attenuates cartilage degeneration and synovial inflammation in rats — animalView study →}.

The finding is replicated across three independent rodent models.

Chelidonine is inactive against 5- and 12-lipoxygenase, the pathway where its co-alkaloids sanguinarine and chelerythrine are potent non-redox inhibitors ^{45Reference 45Vavrečková C et al. · 1996In vitroBenzophenanthridine alkaloids of Chelidonium majus; IView study →}, so greater celandine’s anti-inflammatory activity is at least two mechanistically distinct contributions.

There are no human data, and poor oral bioavailability leaves it unclear whether the oral herb delivers effective concentrations ^{46,47Reference 46Paul A et al. · 2013In vitroCytotoxicity and apoptotic signalling cascade induced by chelidonine-loaded PLGA nanoparticles in HepG2 cells in vitro and bioavailability of nano-chelidonine in mice in vivo — in vitro/animalView study →Reference 47Gao L et al. · 2019In vitroCharacterization of the cytotoxicity of selected Chelidonium alkaloids in rat hepatocytes — in vitroView study →}.

Chelidonine is bioactivated by CYP3A4, 1A2, 2C19 and 2D6 to reactive ortho-quinones ^{48Reference 48Liu Y et al. · 2019In vitroIn vitro and in vivo studies of the metabolic activation of chelidonine — in vitro/animalView study →} and is an irreversible CYP2D6 inactivator ^{49Reference 49Liu Y et al. · 2019In vitroMechanism-based inactivation of cytochrome P450 2D6 by chelidonine — in vitroView study →}, a poor profile for chronic anti-inflammatory use.

Carried by greater celandine.

Costunolide blocks IκB phosphorylation and degradation, cutting NF-κB DNA binding, and suppresses iNOS induction rather than the enzyme itself, inhibiting LPS-driven nitric-oxide output at IC50 1.2–2.8 µM in mouse peritoneal macrophages, a band it shares with dehydrocostus lactone and the saussureamines ^{50,51Reference 50Koo TH et al. · 2001In vitroA sesquiterpene lactone, costunolide, from Magnolia grandiflora inhibits NF-kappa B by targeting I kappa B phosphorylation — in vitroView study →Reference 51Matsuda H et al. · 2003In vitroEffects of sesquiterpenes and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages — in vitroView study →}.

A second, partly separable arm runs through Nrf2 and heme oxygenase-1: costunolide induces HO-1, and its suppression of TNF-α and IL-6 is abolished when HO-1 activity is blocked, so the cytokine effect is at least partly HO-1-dependent rather than a direct transcriptional block ^{52Reference 52Pae HO et al. · 2007In vitroCostunolide inhibits production of tumor necrosis factor-alpha and interleukin-6 by inducing heme oxygenase-1 in RAW264.7 macrophages — in vitroView study →}.

That HO-1 dependence is one of the few mechanistic details specific to costunolide rather than to the warhead.

All of it is cell culture.

No anti-inflammatory endpoint has been measured in an intact animal given costunolide alone, and rat plasma after whole-herb dosing sits in the low ng/mL range against micromolar assay concentrations ^{53Reference 53Zhang J et al. · 2014AnimalPharmacokinetic study on costunolide and dehydrocostuslactone after oral administration of traditional medicine Aucklandia lappa Decne. by LC/MS/MS — animal model in ratsView study →}.

Carried by feverfew and magnolia.

In LPS-induced pleurisy curine cut neutrophil recruitment together with TNF-α, IL-1β, IL-6, CCL2/MCP-1 and leukotriene B₄, and in LPS-stimulated macrophages it lowered cytokine output and iNOS expression; a calcium-channel blocker reproduced the effect, placing Ca²⁺-dependent macrophage activation upstream ^{59Reference 59Ribeiro-Filho J et al. · 2019AnimalCurine inhibits macrophage activation and neutrophil recruitment in a mouse model of lipopolysaccharide-induced inflammation — animal modelView study →}.

The mechanism has a named cell type, and the evidence is acute rodent inflammation only, with no chronic model and no human data.

Carried by abuta.

In human monocytes and macrophages cycleanine inhibits TNF-α synthesis with an IC₅₀ of 4.6 µM and IL-1β at 25.0 µM ^{60Reference 60Seow WK et al. · 1993Inhibitory effects of bisbenzylisoquinolines on synthesis of the inflammatory cytokines interleukin-1 and tumour necrosis factor-alphaView study →}, competitive with the other bisbenzylisoquinolines on TNF-α and notably weaker on IL-1β. It suppresses inducible nitric oxide in LPS-stimulated murine macrophages at 5 µg/mL, with the effect persisting for 48 hours or more ^{61Reference 61Kondo Y et al. · 1993Inhibitory effect of bisbenzylisoquinoline alkaloids on nitric oxide production in activated macrophagesView study →}, and inhibits the alveolar-macrophage respiratory burst at roughly berbamine’s potency ^{62Reference 62Ma JY et al. · 1992Inhibition of respiratory burst activity in alveolar macrophages by bisbenzylisoquinoline alkaloids: characterization of drug-cell interactionView study →}.

In vivo it protects BCG-primed, LPS-challenged mice: 10 mg/kg/day for three days strongly suppressed ALT/AST and cut the serum TNF peak ^{63Reference 63Kondo Y et al. · 1993AnimalSuppression of lipopolysaccharide-induced fulminant hepatitis and tumor necrosis factor production by bisbenzylisoquinoline alkaloids in bacillus Calmette-Guerin-treated miceView study →}, and seven daily doses improved survival ^{64Reference 64Kondo Y et al. · 1990AnimalInhibitory effect of bisbenzylisoquinoline alkaloids on the quick death of mice treated with BCG/LPSView study →}.

The evidence is cell assays plus rodent endotoxin models, with no arthritis, colitis or other disease-relevant inflammation model and no human data, and read directionally it is immunosuppression as much as anti-inflammation.

Unlike the related alkaloids, cycleanine has no histamine-release-inhibiting activity ^{65Reference 65Nakamura K et al. · 1992Histamine release inhibition activity of bisbenzylisoquinoline alkaloidsView study →}, so it contributes nothing to an antihistamine or antiallergic action.

Carried by abuta.

Cynaropicrin suppresses LPS/IFN-γ-induced TNF-α and NO release from macrophage-like cells at IC50 1.1–8.24 µM, and the activity is abolished by added thiols (L-cysteine, 2-mercaptoethanol, DTT), a direct demonstration that it works by cysteine alkylation rather than receptor binding ^{66Reference 66Cho JY et al. · 2000In vitroIn vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappaView study →}.

It was the first natural product shown to modulate the adhesion molecules CD29 (β1 integrin) and CD98 (IC50 2.98 and 3.46 µM, ERK-dependent) without cytotoxicity at those concentrations ^{67Reference 67Cho JY et al. · 2004In vitroCynaropicrin, a sesquiterpene lactone, as a new strong regulator of CD29 and CD98 functions — in vitroView study →}, suppresses iNOS induction through JAK-STAT as well as NF-κB ^{68Reference 68Matsumoto T et al. · 2021In vitroInhibitory effects of cynaropicrin and related sesquiterpene lactones from leaves of artichoke (Cynara scolymus L.) on induction of iNOS in RAW264.7 cells and its high-affinity proteins — in vitroView study →}, and blocks P. gingivalis LPS-driven IL-6 and IL-8 in human gingival fibroblasts plus RANKL-induced osteoclastogenesis ^{69Reference 69Hayata M et al. · 2019In vitroCynaropicrin from Cynara scolymus L. suppresses Porphyromonas gingivalis LPS-induced production of inflammatory cytokines in human gingival fibroblasts and RANKL-induced osteoclast differentiation in RAW264.7 cells — in vitroView study →}.

This is class reactivity.

Every sesquiterpene lactone carrying the α-methylene-γ-lactone acts on NF-κB, so the in-vitro result does not distinguish cynaropicrin from parthenolide, costunolide or helenalin ^{70Reference 70Li J et al. · 2019In vitroCynaropicrin and inhibition of NF-κB activation: a structure activity relationship study — in vitroView study →}.

The evidence is in vitro only, with no pharmacokinetics, so the micromolar potencies may be unreachable in vivo.

Carried by artichoke.

Danshensu is the weakest of the danshen phenolics on this action.

Sodium danshensu stabilised atherosclerotic vulnerable plaques by targeting IKKβ-mediated inflammation in macrophages ^{71Reference 71Zeng M et al. · 2023Sodium danshensu stabilizes atherosclerotic vulnerable plaques by targeting IKKβ-mediated inflammation in macrophagesView study →}, and danshensu promoted cholesterol efflux in RAW264.7 macrophages ^{72Reference 72Gao H et al. · 2016Danshensu promotes cholesterol efflux in RAW264.7 macrophagesView study →}, the ABC-transporter step that reverse cholesterol transport depends on.

In the kidney, its protection against cisplatin nephrotoxicity ran through Nrf2 activation with NF-κB inhibition ^{73Reference 73Yu C et al. · 2021Danshensu attenuates cisplatin-induced nephrotoxicity through activation of the Nrf2 pathway and inhibition of NF-κBView study →}.

The anti-inflammatory character is largely downstream of the antioxidant mechanism rather than an independent pharmacology, and every finding is a single study from a single group without replication.

Dihydrotanshinone I has two direct target-binding mechanisms, which is rare in this field.

It binds IRF3 itself, and does so without disturbing the STING–TBK1, IRF3–TBK1 or MAVS–TBK1 interactions; it specifically prevents STING from being recruited to IRF3, cutting type-I interferon and ISG output downstream, and it was effective in three IRF3-driven mouse models (Trex1-deficiency systemic inflammation, obesity-induced insulin resistance and NASH) ^{74Reference 74Shi W et al. · 2025AnimalDihydrotanshinone I, a main compound of Salvia miltiorrhiza, alleviates autoimmune and inflammatory diseases by directly targeting IRF3 — cell and mouse studyView study →}.

It also blocks the RNA-binding protein HuR from associating with its target mRNAs at Ki 3.74 nM ^{75Reference 75D’Agostino VG et al. · 2015In vitroDihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function — in vitro and cell studyView study →}, and HuR stabilises the TNF-α message among many other inflammatory transcripts; target engagement was confirmed structurally by NMR and molecular-dynamics mapping onto RRM1/RRM2 ^{76Reference 76Lal P et al. · 2017Regulation of HuR structure and function by dihydrotanshinone-I — NMR, molecular dynamics, RIP-chip and xenograft studyView study →}.

Conventional readouts follow: mouse DSS colitis improved at 10–25 mg/kg with reduced myeloperoxidase, iNOS, COX-2, TNF-α, IL-1β, IL-6 and HMGB1 ^{77Reference 77Guo Y et al. · 2018AnimalDihydrotanshinone I, a natural product, ameliorates DSS-induced experimental ulcerative colitis in mice — mouse studyView study →}, and IgE-antigen-stimulated mast-cell activation was suppressed through Syk kinase inhibition ^{78Reference 78Li X et al. · 2015In vitroLi X, Yang JH, Jin Y, et al. (2015). 15,16-Dihydrotanshinone I suppresses IgE-Ag stimulated mouse bone marrow-derived mast cell activation by inhibiting Syk kinase — in vitro study. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/25917838/View study →}.

One head-to-head sets the limit: the purified total tanshinone fraction out-performed dihydrotanshinone I, tanshinone I, cryptotanshinone and tanshinone IIA each taken singly, in LPS-stimulated macrophages and three mouse models ^{58Reference 58Gao H et al. · 2018In vitroSimultaneous purification of dihydrotanshinone, tanshinone I, cryptotanshinone, and tanshinone IIA from Salvia miltiorrhiza and their anti-inflammatory activities investigation — in vitro and animal modelView study →}.

The anti-inflammatory activity of danshen belongs to the fraction.

Carried by dan shen.

Dioscin inhibited nitric-oxide production in LPS-stimulated RAW264.7 macrophages with an IC50 of 0.469 µM, more potent than protodioscin (0.712 µM) or gracillin (0.815 µM), with parallel reductions in TNF-α, IL-1β and IL-6 ^{79Reference 79Yang G et al. · 2022Identification of anti-inflammatory components in Dioscorea nipponica Makino based on HPLC-MS/MS, quantitative analysis of multiple components by single marker and chemometric methodsView study →}.

The concentration matters: 0.47 µM sits far below the range where saponin membrane lysis begins, so this is one of the few dioscin cell results that cannot be dismissed as a detergent artefact.

In vivo the endotoxin liver model attributes the effect to TLR4/MyD88 ^{80Reference 80Yao H et al. · 2016Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathwayView study →}, the pathway a macrophage NO result predicts.

Whether 0.47 µM is reachable anywhere but gut epithelium at 0.2% oral bioavailability is unaddressed, and the source herb is D. nipponica rather than wild yam.

Carried by wild yam and tribulus.

Diosgenin suppresses NF-κB and its downstream mediators COX-2 and iNOS, with parallel reduction of TGF-β, replicated across rodent and cell models ^{81Reference 81Karami-Mohajeri S et al. · 2022ReviewDiosgenin: mechanistic insights on its anti-inflammatory effects — reviewView study →}; in cerebral ischaemia–reperfusion the same suppression runs through a HIKESHI/HSP70/NF-κB chaperone axis ^{82Reference 82Zhang X et al. · 2022AnimalDiosgenin revealed potential effect against cerebral ischemia reperfusion through the HIKESHI/HSP70/NF-κB anti-inflammatory axis — rat in vivo studyView study →}.

The fenugreek steroidal saponin glycosides that carry diosgenin as their aglycone suppress TNF-α in culture ^{83Reference 83Kawabata T et al. · 2011In vitroAnti-inflammatory and anti-melanogenic steroidal saponin glycosides from fenugreek (Trigonella foenum-graecum L.) seeds — in vitro studyView study →}.

Every mechanistic study used isolated diosgenin at 10–200 mg/kg/day in rodents, well above what any wild yam or fenugreek preparation delivers, and the only human data is a 10-participant crossover on whole Dioscorea esculenta powder showing reduced plasma PGE2 and COX-2 ^{84Reference 84Sato K · 2024RCTThe effect of Dioscorea esculenta powder on prostaglandin E2 and cytochrome c oxidase subunit 2 levels, menstrual pain, and premenstrual syndrome in young women: a randomized double-blind controlled trialView study →}.

Diosgenin inhibits CYP3A4 in vitro (IC50 ≈ 17 µM) and is a P-glycoprotein substrate, a theoretical, untested interaction with CYP3A4 and P-gp substrate drugs ^{85Reference 85Manda VK et al. · 2013In vitroCharacterization of in vitro ADME properties of diosgenin and dioscin from Dioscorea villosa — in vitro studyView study →}.

Carried by wild yam and fenugreek.

Geraniin has an unusually specific molecular target for a tannin: it binds IL-1β directly and blocks the IL-1β/IL-1R interaction, restoring tight-junction proteins in IL-1β-stimulated Caco-2 cells and reducing barrier injury in DSS colitis mice through MAPK/NF-κB/MLC ^{90Reference 90Lee HR et al. · 2024AnimalGeraniin alleviates inflammation in Caco-2 cells and dextran sulfate sodium-induced colitis mice by targeting IL-1βView study →}.

In LPS-stimulated macrophages it also suppresses iNOS, ROS and NF-κB nuclear translocation while inducing HO-1 through Nrf2, blocking the inflammatory arm and switching on the cytoprotective one ^{91Reference 91Wang P et al. · 2016Inhibitory effects of geraniin on LPS-induced inflammation via regulating NF-κB and Nrf2 pathways in RAW 264.7 cellsView study →}; TNF-α-release inhibition is modest at IC₅₀ 43 µM ^{92Reference 92Fujiki H et al. · 2003New TNF-alpha releasing inhibitors as cancer preventive agents from traditional herbal medicineView study →}.

The limit is compartment rather than pathway.

Geraniin shows no apparent permeability across a Caco-2 monolayer ^{93Reference 93Elendran S et al. · 2019Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture modelView study →}, so these micromolar concentrations are reachable in the gut lumen and essentially nowhere else, which is why the colitis result is the most translatable one and why systemic anti-inflammatory claims belong to its urolithin-type metabolites ^{94,95Reference 94Ito H · 2011Metabolites of the ellagitannin geraniin and their antioxidant activitiesView study →Reference 95Ishimoto H et al. · 2011AnimalIn vivo anti-inflammatory and antioxidant properties of ellagitannin metabolite urolithin AView study →} rather than to the parent.

Carried by chanca piedra and amla.

Gracillin’s concentrations are the most defensible on the whole molecule.

Screening seven saponins of Dioscorea nipponica rhizome against LPS-stimulated RAW264.7 macrophages, chemometric selection picked protodioscin, dioscin and gracillin as the actives, and verification with purified standards gave NO-inhibition IC₅₀ values of 0.712, 0.469 and 0.815 µM respectively, with significant reductions in TNF-α, IL-1β and IL-6 ^{79Reference 79Yang G et al. · 2022Identification of anti-inflammatory components in Dioscorea nipponica Makino based on HPLC-MS/MS, quantitative analysis of multiple components by single marker and chemometric methodsView study →}.

At 0.8 µM membrane lysis is not a plausible explanation, so this is the one gracillin result that is clearly not a detergent artefact.

Independently, gracillin purified to more than 95% by counter-current chromatography was active in anti-inflammatory, urate-lowering and anti-diabetic assays ^{96Reference 96Wang Z et al. · 2024Efficient discovery of active isolates from Dioscorea spongiosa by the combination of bioassay-guided macroporous resin column chromatography and high-speed counter-current chromatographyView study →}, and a purified D. hypoglauca saponin fraction containing it out-performed the crude extract in the same macrophage model ^{97Reference 97Qin Z et al. · 2025Purification of steroidal saponins from Dioscoreae hypoglaucae rhizoma by macroporous resin and evaluation of their anti-inflammatory effectView study →}.

The in-vivo evidence is topical.

Gracillin isolated from Dioscorea quinqueloba was co-applied with 2,4-dinitrochlorobenzene to hairless mice for two weeks and markedly reduced redness, itching, swelling and lichenification, cut transepidermal water loss, raised skin hydration and suppressed IL-4 in both RBL-2H3 cells and the animals’ skin ^{98Reference 98Jegal J et al. · 2018AnimalAnti-atopic properties of gracillin isolated from Dioscorea quinqueloba on 2,4-dinitrochlorobenzene-induced skin lesions in miceView study →}.

The topical route sidesteps the sub-1% bioavailability ceiling entirely, which makes this gracillin’s most translatable finding, and it has had no follow-up since 2018.

Systemically, in LPS-challenged mice gracillin improved cardiac function, reduced apoptosis and blocked NF-κB, with the protection abrogated by miR-29a suppression, a real epistasis control ^{99Reference 99Song YX et al. · 2020AnimalGracillin inhibits apoptosis and inflammation induced by lipopolysaccharide to alleviate cardiac injury in mice via improving miR-29aView study →}.

There is no receptor-level mechanism, no dose–response in an animal inflammation model outside the skin and no comparator drug.

The NF-κB/iNOS story is a class mechanism established for dioscin and inferred for gracillin.

Carried by wild yam.

Hamamelitannin’s cleanest mechanism is enzymatic: it inhibits 5-lipoxygenase, the leukotriene arm, at IC50 1.0–18.7 µM while leaving lyso-PAF:acetyl-CoA acetyltransferase untouched, a specific block rather than generic polyphenol activity ^{100Reference 100Hartisch C et al. · 1997In vitroDual inhibitory activities of tannins from Hamamelis virginiana and related polyphenols on 5-lipoxygenase and lyso-PAF: acetyl-CoA acetyltransferase — in vitroView study →}.

In keratinocytes it acts on IL-4 pathway targets (CCL26, K10, proliferation) ^{101Reference 101Piazza S et al. · 2022In vitroUnveiling the ability of witch hazel (Hamamelis virginiana L.) bark extract to impair keratinocyte inflammatory cascade typical of atopic eczema — in vitroView study →}, and it gives complete protection against TNF-induced endothelial cell death above 10 µM without affecting ICAM-1 or adhesion, which is cell survival rather than signalling suppression ^{102Reference 102Habtemariam S · 2002In vitroHamamelitannin from Hamamelis virginiana inhibits the tumour necrosis factor-alpha (TNF)-induced endothelial cell death in vitro — in vitroView study →}.

The widely repeated NF-κB result belongs to the whole bark extract rather than to this molecule ^{101Reference 101Piazza S et al. · 2022In vitroUnveiling the ability of witch hazel (Hamamelis virginiana L.) bark extract to impair keratinocyte inflammatory cascade typical of atopic eczema — in vitroView study →}, and one careful study found purified hamamelitannin inactive where the extract worked, crediting the proanthocyanidins ^{103Reference 103Piazza S et al. · 2022In vitroAnti-inflammatory and anti-acne effects of Hamamelis virginiana bark in human keratinocytes — in vitroView study →}, directly contradicted by a 2025 study that ranked it among the most active ^{104Reference 104Skowrońska W et al. · 2025In vitroChemical composition, skin microbiota metabolism, antimicrobial potential and anti-inflammatory properties of witch hazel bark (Hamamelis virginiana L.) — in vitro/ex vivoView study →}.

The question is unresolved.

Carried by witch hazel.

Isosecotanapartholide is a covalent cysteine alkylator: its α-methylene-γ-lactone adds to protein thiols, and this is demonstrably the mechanism rather than an inference, since an analogue with the exocyclic methylene replaced by a methyl group is inactive, and inhibition of NF-κB–DNA binding disappears when a competing thiol is present in the assay ^{113Reference 113Makiyi EF et al. · 2009In vitroIso-seco-tanapartholides: isolation, synthesis and biological evaluation — in vitroView study →}.

The alkylated residues have been mapped: Keap1 Cys151/273/288, whose modification drives a disulfide-linked Keap1 dimer that releases Nrf2 to the nucleus ^{114Reference 114Zhu D et al. · 2022AnimalIso-seco-tanapartholide activates Nrf2 signaling pathway through Keap1 modification and oligomerization to exert anti-inflammatory effects — mice, in vivoView study →}, and cysteines on p62/SQSTM1, whose covalent oligomerisation recruits KEAP1 for autophagic degradation and reinforces the same NRF2 output ^{115Reference 115Zhu D et al. · 2023AnimalIso-seco-tanapartholide induces p62 covalent oligomerization to activate KEAP1-NRF2 redox pathway in rheumatoid arthritis — mice, in vivoView study →}.

Downstream it suppresses iNOS expression and NO production in LPS-stimulated macrophages at low micromolar concentrations ^{116,117Reference 116Ahn H et al. · 2003In vitroInhibitors of inducible nitric oxide synthase expression from Artemisia iwayomogi — in vitroView study →Reference 117Liu ZY et al. · 2025In vitroIridoids and other constituents from the aerial parts of Patrinia rupestris and their inhibitory effects on nitric oxide production — in vitroView study →}, acts late on NF-κB, blocking transcriptional activity and DNA binding rather than IκBα degradation (IC₅₀ 7.7 µM) ^{113Reference 113Makiyi EF et al. · 2009In vitroIso-seco-tanapartholides: isolation, synthesis and biological evaluation — in vitroView study →}, and inhibits PFKFB3-mediated glycolysis with loss of p-STAT3 and p-p65 ^{118Reference 118Kong M et al. · 2023AnimalIso-seco-tanapartholide from Artemisia argyi inhibits the PFKFB3-mediated glycolytic pathway to attenuate airway inflammation in lipopolysaccharide-induced acute lung injury mice — in vivoView study →}.

In vivo it reduced LPS-induced acute lung injury and rheumatoid-arthritis pathology in mice ^{118,115Reference 118Kong M et al. · 2023AnimalIso-seco-tanapartholide from Artemisia argyi inhibits the PFKFB3-mediated glycolytic pathway to attenuate airway inflammation in lipopolysaccharide-induced acute lung injury mice — in vivoView study →Reference 115Zhu D et al. · 2023AnimalIso-seco-tanapartholide induces p62 covalent oligomerization to activate KEAP1-NRF2 redox pathway in rheumatoid arthritis — mice, in vivoView study →}.

No pharmacokinetics exist at all.

Oral bioavailability has never been measured, and the molecule is both a soft electrophile (a glutathione substrate) and unusually polar for a sesquiterpene lactone (XLogP −0.5) in a family whose cell potency tracks lipophilicity ^{119,120Reference 119Ghantous A et al. · 2009In vitroStructure-activity relationship of seco-tanapartholides isolated from Achillea falcata for inhibition of HaCaT cell growth — in vitroView study →Reference 120PubChem CID 13918473 — Isosecotanapartho et al.Database entryView study →}, so whether the 3–10 µM in-vitro range is reachable in tissue is unknown.

Three laboratories claim three different direct targets for the same phenotype, the signature of a promiscuous alkylator rather than a selective ligand, and the mechanism is a class one shared with parthenolide, helenalin and most α-methylene lactones.

Carried by mugwort, yarrow and feverfew.

Lactucopicrin has the largest body of in-vivo work among the sesquiterpene-lactone anti-inflammatories and the most unusual mechanism.

Rather than the class-standard alkylation of p65’s DNA-binding cysteine, it stops p65 reaching the nucleus: it destabilises importin-α3 mRNA in TNF-α-stimulated endothelial cells, improving outcomes in LPS-induced septic mice ^{121Reference 121Weng H et al. · 2021AnimalNatural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice — animal in vivoView study →}, and blocks cytoplasmic dynein-mediated p65 nuclear transport in inflamed macrophages, alleviating atherogenesis in ApoE-deficient mice ^{122Reference 122He L et al. · 2021AnimalLactucopicrin inhibits cytoplasmic dynein-mediated NF-κB activation in inflammated macrophages and alleviates atherogenesis in apolipoprotein E-deficient mice — animal in vivoView study →}.

A 2025 study across three cell types identified it as a potent NF-κB antagonist and a novel AHR modulator, and silencing AHR attenuated the NF-κB inhibition, which establishes a receptor-level dependency rather than a purely chemical one ^{123Reference 123Ávila-Gálvez MÁ et al. · 2025In vitroLactucopicrin: a sesquiterpene lactone with anti-inflammatory activity modulates the crosstalk between NF-kB and AHR pathways — in vitroView study →}.

It also reduces LOX-1 in lipid rafts, limiting macrophage foam-cell formation ^{124Reference 124Li Q et al. · 2022In vitroTerpene lactucopicrin limits macrophage foam cell formation by a reduction of lectin-like oxidized low-density lipoprotein receptor-1 in lipid rafts — in vitroView study →}.

Two mouse models sit against a baseline of class reactivity, since every exomethylene sesquiterpene lactone suppresses NF-κB in cell assays by cysteine alkylation ^{125,126Reference 125Rüngeler P et al. · 1999In vitroInhibition of transcription factor NF-kappaB by sesquiterpene lactones: a proposed molecular mechanism of action — in vitroView study →Reference 126Schmidt TJ · 1999In vitroHelenanolide type sesquiterpene lactonesView study →}.

What is specific to lactucopicrin is the import-machinery and AHR route, and that comes from a single research group ^{121,122,124Reference 121Weng H et al. · 2021AnimalNatural lactucopicrin alleviates importin-α3-mediated NF-κB activation in inflammated endothelial cells and improves sepsis in mice — animal in vivoView study →Reference 122He L et al. · 2021AnimalLactucopicrin inhibits cytoplasmic dynein-mediated NF-κB activation in inflammated macrophages and alleviates atherogenesis in apolipoprotein E-deficient mice — animal in vivoView study →Reference 124Li Q et al. · 2022In vitroTerpene lactucopicrin limits macrophage foam cell formation by a reduction of lectin-like oxidized low-density lipoprotein receptor-1 in lipid rafts — in vitroView study →} plus one unreplicated 2025 paper ^{123Reference 123Ávila-Gálvez MÁ et al. · 2025In vitroLactucopicrin: a sesquiterpene lactone with anti-inflammatory activity modulates the crosstalk between NF-kB and AHR pathways — in vitroView study →}.

The evidence is isolate only, at doses no dietary or herbal exposure reaches, with no bioavailability figure.

Carried by wild lettuce.

Dihydroberberine suppresses NF-κB and MAPK signalling simultaneously, cutting IL-6, IL-1β and TNF-α production and mRNA across three mouse inflammation models, though that study reports it as weaker than berberine in the same assays ^{128Reference 128Tan L et al. · 2019Dihydroberberine, a hydrogenated derivative of berberine firstly identified in Phellodendri Chinese Cortex, exerts anti-inflammatory effect via dual modulation of NF-κB and MAPK signaling pathwaysView study →}.

In the gut it acts on the TLR4/MyD88/NF-κB axis and restores tight-junction protein expression, improving disease-activity scores in DSS colitis in mice, where the authors rated it comparable to azathioprine and better than berberine ^{129Reference 129Li C et al. · 2021AnimalDihydroberberine, an isoquinoline alkaloid, exhibits protective effect against dextran sulfate sodium-induced ulcerative colitis in miceView study →}.

A separate mouse model adds NLRP3 inflammasome suppression alongside xanthine-oxidase inhibition in hyperuricaemia ^{130Reference 130Xu L et al. · 2021AnimalAnti-hyperuricemic and nephroprotective effects of dihydroberberine in potassium oxonate- and hypoxanthine-induced hyperuricemic miceView study →}.

The data are thin and contradictory: two mouse studies disagree on whether it is stronger or weaker than berberine, nothing is replicated, no plant extract was used, and no human inflammatory endpoint has been tested.

Carried by barberry.

Menisperine inhibits NF-κB in a luciferase reporter system, identified in a bioactivity-guided UPLC-Q/TOF-MS screen of Caulis Sinomenii and named there as a novel NF-κB inhibitor, with IL-6 and IL-8 assays confirming the downstream effect ^{131Reference 131Sun D et al. · 2016Screening and identification of Caulis Sinomenii bioactive ingredients with dual-target NF-κB inhibition and β2-AR agonizing activitiesView study →}.

An independent spectrum–effect study across 19 batches of the same herb used nitric-oxide inhibition as the readout and then verified the individual compounds: sinomenine, magnoflorine, menisperine and stepharanine were the major anti-inflammatory constituents ^{132Reference 132Wang LJ et al. · 2019Identification of anti-inflammatory components in Sinomenii Caulis based on spectrum-effect relationship and chemometric methodsView study →}.

Two groups and two assays both moved past the extract to the isolate, a stronger design than most single-molecule claims of this size.

No IC50 is reported in either study, so direction is established and potency is not; no animal inflammation model has been run on the isolate; and menisperine is a permanently charged quaternary aporphine with no measured permeability and no pharmacokinetic parameters, so how much reaches an inflamed tissue after oral intake is unknown ^{133,134Reference 133Ma C et al. · 2008AnimalIdentification of major alkaloids and steroidal saponins in rat serum by HPLC-diode array detection-MS/MS following oral administration of Huangbai-Zhimu herb-pair extractView study →Reference 134Xu T et al. · 2020ReviewMagnoflorine: a review of its pharmacology, pharmacokinetics and toxicityView study →}.

Carried by muira puama and barberry.

(+)-N-Methyllaurotetanine inhibited superoxide anion generation in activated human neutrophils with IC50 8.36 ± 0.11 µM, alongside co-isolated (+)-isoboldine (5.81 µM) from Lindera aggregata ^{135Reference 135Kuo PC et al. · 2020Anti-inflammatory principles from Lindera aggregataView study →}, one of the few results for this molecule measured in a primary human cell.

It is a single paper, never replicated, with no pathway dissection and no animal inflammation model.

The concentration is about 100 times its serotonin-receptor affinity, so any anti-inflammatory role would need far higher exposure than a CNS one.

Carried by California poppy and boldo.

Isolated protodioscin (50, 100 and 200 mg/kg) reduced paw swelling, ankle inflammation and lymphocyte infiltration in complete-Freund’s-adjuvant arthritis rats, lowering IL-1β, TNF-α, IL-6, COX-2, PGE2, myeloperoxidase, articular elastase, lipid peroxidase and nitrite ^{144Reference 144Liu JY et al. · 2017AnimalProtodioscin ameliorates oxidative stress, inflammation and histology outcome in complete Freund’s adjuvant induced arthritis rats — [animal model]View study →}.

It is one of the few isolated-molecule, whole-animal results for the compound, and the cytokine pattern is coherent, but no upstream target (NF-κB, MAPK or a receptor) was identified, so the pathway tags above are readouts rather than mechanisms.

It is one study in one model without replication, and the doses are one to two orders of magnitude above what any Tribulus product delivers.

Carried by tribulus and fenugreek.

Punicalagin is the one application where the isolated molecule was given to a living animal and changed a disease endpoint.

Oral isolated punicalagin at 100 mg/kg/day alleviated DSS-induced colitis in mice, and the anti-colitic effect was transferable to antibiotic-treated mice by faecal transplant and by sterile faecal filtrate, identifying the microbiota and its metabolites, rather than punicalagin acting on host cells, as the proximate cause ^{145Reference 145Liu H et al. · 2024AnimalGut microbiota and D-ribose mediate the anti-colitic effect of punicalagin in DSS-treated miceView study →}.

A pomegranate peel extract carrying punicalin, punicalagin and ellagic acid separately reduced colonic damage, weight loss and bacterial translocation to the spleen in Citrobacter rodentium infectious colitis, without reducing colonisation or blunting the Th1/Th17 response, which is damage limitation rather than clearance ^{146Reference 146Smith AD et al. · 2020AnimalPomegranate peel extract reduced colonic damage and bacterial translocation in a mouse model of infectious colitis induced by Citrobacter rodentiumView study →}.

This is a luminal, microbiota-mediated anti-inflammatory action, structurally the same as castalagin’s, and never a systemic one.

The evidence is rodent only, with no human IBD data.

Quercetin inhibits NF-κB-driven pro-inflammatory transcription, the same hub curcumin acts on, and this is the pathway most often invoked for the flavonoid class as a whole.

The human evidence is markedly weaker than the mechanism suggests.

Pooled analyses find no robust overall effect on CRP or IL-6, with reductions surfacing only in subgroups, in people with diagnosed disease and at higher doses ^{147,148Reference 147Tabrizi R et al. · 2020Meta-analysisThe effects of quercetin supplementation on lipid profiles and inflammatory markers among patients with metabolic syndrome and related disorders — systematic review and meta-analysis of RCTsView study →Reference 148Mohammadi-Sartang M et al. · 2017Meta-analysisEffects of supplementation with quercetin on plasma C-reactive protein concentrations — systematic review and meta-analysis of randomised controlled trialsView study →}.

Quercetin is a contributor to the class effect and the best-documented instance in this field of a well-established pathway that does not reliably produce a measurable clinical inflammatory outcome.

Carried by onion, apple, elderflower, ginkgo and St. John’s wort.

Four independent in-vivo studies since 2018 converge on one pathway.

Reticuline from Litsea cubeba cut xylene-induced ear oedema and carrageenan paw oedema, reduced neutrophil infiltration, lowered TNF-α and IL-6 mRNA and reduced JAK2/STAT3 phosphorylation, with a boldine 0.5 + reticuline 0.25 mg/kg combination out-performing either alone ^{149Reference 149Yang X et al. · 2018Anti-inflammatory effects of boldine and reticuline isolated from Litsea cubeba through JAK2/STAT3 and NF-κB signaling pathways — animal studyView study →}.

In diet-induced-obesity asthmatic mice, 0.25 mg/kg by gavage reduced airway resistance and IL-17A, IL-1β and IL-5 through JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB ^{150Reference 150Lyu X et al. · 2024AnimalAnti-inflammatory effects of reticuline on the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathway in a mouse model of obesity-associated asthma — animal studyView study →}.

In a rat controlled-cortical-impact TBI model, i.p. reticuline damped astrocyte and microglial reactivity and improved recovery, with the effect reversed by the STAT3 agonist colivelin, a clean mechanistic control ^{151Reference 151Xu S et al. · 2025Reticuline modulates astrocyte and microglial responses to enhance prognosis after traumatic brain injury — animal studyView study →}.

In collagen-induced arthritis, 0.5–1 mg/kg/day cut arthritis scores and bone erosion, with 10–20 µM suppressing IL-6 and migration in TNF-α-stimulated human synovial fibroblasts ^{152Reference 152Tian J et al. · 2026In vitroReticuline alleviates rheumatoid arthritis by suppressing the JAK/STAT signaling pathway — in vitro and collagen-induced arthritis modelView study →}.

No study states the enantiomer, none reports plasma exposure, and 0.25–1 mg/kg is very low for an alkaloid with no measured bioavailability.

The findings are single-group and without independent replication.

Carried by graviola and California poppy.

Salvianolic acid A’s anti-inflammatory action is neutrophil- and complement-directed rather than the usual NF-κB/COX story.

In LPS-induced acute lung injury in mice, 10 mg/kg matched dexamethasone on lung injury score, wet/dry ratio, BALF protein and cell counts, and cytokines, acting by suppressing neutrophil extracellular trap release through inhibition of Src and the downstream Raf/MEK/ERK cascade.

The effect reproduced on neutrophils taken from ARDS patients and from healthy volunteers in vitro, and a Src-targeting YEEI peptide abolished it completely, a clean mechanistic confirmation ^{156Reference 156Liu Q et al. · 2022Salvianolic acid A protects against lipopolysaccharide-induced acute lung injury by inhibiting neutrophil NETosisView study →}.

Separately, Sal A showed anti-complement activity against both the classical and alternative pathways, with molecular docking to C3b, and substantially improved survival in LPS-induced disseminated intravascular coagulation in rats ^{157Reference 157Zhang QY et al. · 2022Salvianolic acid A alleviates lipopolysaccharide-induced disseminated intravascular coagulation by inhibiting complement activationView study →}.

In ovalbumin asthma it reduced eosinophil infiltration, mucin and Th2 cytokines (IL-4, IL-13) ^{158Reference 158Heo JY · 2019In vitroAnti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experimentsView study →}.

One negative is informative: Sal A failed to inhibit mast-cell degranulation in the same asthma study, where tanshinone I and tanshinone IIA succeeded ^{158Reference 158Heo JY · 2019In vitroAnti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experimentsView study →}.

Danshen’s two fractions do different things.

Carried by dan shen.

Salvianolic acid B runs underneath the fibrosis and cardioprotection lines rather than standing alone.

In bleomycin lung injury it reduced inflammatory-cell infiltration and alveolar structural disruption alongside collagen deposition, and in vitro it suppressed TGF-β-driven myofibroblast differentiation and epithelial-to-mesenchymal transition through both Smad-dependent and Smad-independent MAPK signalling ^{159Reference 159Liu Q et al. · 2016Salvianolic acid B attenuates experimental pulmonary fibrosis through inhibition of the TGF-β signaling pathwayView study →}.

In the acute-MI meta-analysis, salvianolate lowered CRP (MD −6.17) and malondialdehyde alongside its cardiac effects ^{160Reference 160Chen P et al. · 2024Meta-analysisEfficacy and safety of salvianolate injection in treating acute myocardial infarction — meta-analysis and systematic literature review of 30 RCTsView study →}.

The 2023 pharmacological review frames anti-inflammatory and antioxidant action as the two mechanisms common to Sal B’s protective effects across lung, heart, kidney, intestine, bone, liver and skin ^{161Reference 161He G et al. · 2023ReviewSalvianolic acid B — a review of pharmacological effects, safety, combination therapy, new dosage forms and novel drug delivery routesView study →}.

It is a supporting mechanism rather than a primary indication; there is no inflammatory-disease trial of this molecule.

At group level the salvianolic acids reduce leukocyte–endothelial adherence and inflammatory signalling in vascular tissue and suppress metalloproteinase expression from aortic smooth muscle ^{162,163Reference 162Ho JH · 2011Salvianolic acids — small compounds with multiple mechanisms for cardiovascular protectionView study →Reference 163Wu Y et al. · 2020The effect of salvianolic acid on vascular protection and possible mechanismsView study →}.

Sal A specifically carries the post-stroke neuroinflammation literature: modulation of pro-inflammatory cytokines and inflammatory signalling, reduced peripheral immune-cell infiltration through a disrupted blood–brain barrier, and preserved endothelial function ^{164Reference 164Yang H et al. · 2024Targeting post-stroke neuroinflammation with salvianolic acid A — molecular mechanisms and preclinical evidenceView study →}.

Sal B specifically attenuated LPS/TLR4 signalling and downregulated TLR4/MyD88 with reduced JNK and NF-κB p65 phosphorylation in white adipose tissue of high-fat-diet mice, alongside improved intestinal epithelial integrity ^{165Reference 165Li L et al. · 2020AnimalSalvianolic acid B prevents body weight gain and regulates gut microbiota and LPS/TLR4 signaling pathway in high-fat diet-induced obese miceView study →}.

The evidence is in vitro and rodent.

The intravenous clinical trials ^{166,167Reference 166Zhang D et al. · 2016Meta-analysisSalvianolate injection in the treatment of unstable angina pectoris — a systematic review and meta-analysisView study →Reference 167Lyu J et al. · 2019Meta-analysisSalvianolic acids for injection combined with conventional treatment for patients with acute cerebral infarction — a systematic review and meta-analysis of randomized controlled trialsView study →} report CRP reduction in patients, which is human anti-inflammatory biomarker data at group level and by infusion.

The comfrey anti-inflammatory literature (two-step NF-κB inhibition, COX-2 and adhesion-molecule suppression in human endothelial cells) belongs to a whole comfrey root extract and is credited primarily to rosmarinic acid; salvianolic-type oligomers are a co-occurring plausible contributor, never a demonstrated one ^{168Reference 168Trifan A et al. · 2018Is comfrey root more than toxic pyrrolizidine alkaloids? Salvianolic acids among antioxidant polyphenols in comfrey (Symphytum officinale L.) rootsView study →}.

Sanguiin H-6’s most reproducible mechanism is the one whose active concentrations are reachable.

In human gastric epithelial cells it totally abolished TNF-α-induced IL-8 release at 2.5 µM ^{127Reference 127Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo studiesView study →}, a luminal-plausible concentration, and in LPS-activated macrophages it suppressed iNOS mRNA induction and enzyme activity (25 µM matching aminoguanidine at 50 µM) while also scavenging nitric oxide directly ^{169Reference 169Yokozawa T et al. · 2002In vitroEffects of sanguiin H-6, a component of Sanguisorbae Radix, on lipopolysaccharide-stimulated nitric oxide production — in vitroView study →}.

The one in-vivo study of the isolate (rat, 10 mg/kg/day oral for 30 days) reduced mitochondrial lipid peroxidation, preserved glutathione and suppressed caspase-3 after an LPS-plus-ischaemia-reperfusion insult ^{170Reference 170Yokozawa T et al. · 2002AnimalPotential of sanguiin H-6 against oxidative damage in renal mitochondria and apoptosis mediated by peroxynitrite in vivo — rat studyView study →}.

The limit is attribution.

When the anti-inflammatory activity of orally taken ellagitannin plant materials, including Rubus idaeus leaf infusion, was dissected, the active species were the gut-microbial urolithins A, B and C, with urolithin A inhibiting TNF-α at 0.625 µM, rather than the parent tannin ^{19Reference 19Piwowarski JP et al. · 2014Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — ex vivoView study →}.

The parent molecule is the precursor; the metabolite does the systemic work, and only in people whose microbiota makes it.

Carried by raspberry leaf.

In LPS-treated SH-SY5Y cells, shatavarin IV cut IL-6 and TNF-α by 46% and 50% and raised IL-10 and TGF-β by 2.7- and 4.4-fold; the effect was abolished by K252a, a receptor-tyrosine-kinase inhibitor, implicating signalling through TrkB rather than a generic redox effect, with the authors proposing that shatavarin IV salvages endogenous BDNF and docks to TrkB as a complex ^{177Reference 177Das D et al. · 2026In vitroShatavarin IV, a bioactive constituent of Asparagus racemosus, exerts antioxidant and anti-inflammatory effects in LPS-treated cultured SH-SY5Y cells via TrkB-BDNF axisView study →}.

The same study ran the isolate (10 ng/mL) against a 5%-shatavarin-IV proprietary extract (100 ng/mL) side by side and got comparable results, a rare like-for-like isolate-versus-extract comparison.

It is a single study in a single cell line, and the TrkB-complex mechanism is partly in silico.

Carried by shatavari.

In both mouse RAW 264.7 and human monocyte-derived macrophages, tellimagrandin II (non-cytotoxic below 50 µM) suppressed LPS-induced NOS2 protein and mRNA and COX-2 protein, cutting downstream NO and PGE₂; upstream it reduced phospho-p65, c-fos, phospho-c-jun and phospho-p38, placing the effect on the NF-κB/AP-1/MAPK axis ^{186Reference 186Lin CY et al. · 2021AnimalLipopolysaccharide-induced nitric oxide and prostaglandin E2 production is inhibited by tellimagrandin II in mouse and human macrophagesView study →}.

In CCl₄-stressed HepG2 cells it reduced ALT/AST and produced one of the largest glutathione increases of the ellagitannins tested, comparable to silymarin ^{187Reference 187Al-Sayed E · 2016Hepatoprotective and antioxidant effect of ellagitannins and galloyl esters isolated from Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in HepG2 cellsView study →}.

The evidence is cell models only, with no animal inflammation model of the isolate.

Carried by meadowsweet and clove.

Urolithin B suppresses inflammatory signalling across several cell types with a detailed mechanism.

In LPS-activated BV2 microglia it cut NO, TNF-α and IL-6 while raising IL-10, blocked NF-κB by preventing IκBα phosphorylation and degradation, suppressed JNK, ERK and Akt phosphorylation and enhanced AMPK; the effect was not stimulus-specific, holding for lipoteichoic acid and poly(I:C) as well as LPS, and microglial activation was also suppressed in LPS-injected mouse brain ^{209Reference 209Lee G et al. · 2019Anti-inflammatory and antioxidant mechanisms of urolithin B in activated microgliaView study →}.

It blocks M1 macrophage polarisation through miR155-5p/MAPK-NF-κB ^{210Reference 210Tuohudaali W et al. · 2025Urolithin B inhibits LPS-induced macrophage M1 polarization via miR155-5p mediated MAPK/NF-κB pathwayView study →} and, in a peri-implant osteoporosis model, through VEGFR2 phosphorylation ^{211Reference 211Xiao L et al. · 2024Urolithin B inhibits the differentiation of M1 macrophages and relieves the inflammation around the implants under osteoporosis via down-regulating the phosphorylation of VEGFR2View study →}.

It is also a direct MMP-9 inhibitor at IC50 13.17 µM, more potent than urolithin A (33.29 µM) and than ellagic acid (17.14 µM) ^{212Reference 212Houssein-Zadeh N et al. · 2025Ellagitannins (ellagic acid, urolithin A, urolithin B) inhibit the catalytic activity of human recombinant metalloproteinase 9View study →}.

On one endpoint urolithin B is the only active urolithin: across four urolithins tested on human neutrophils, urolithin B at 20 µM alone inhibited IL-8 and MMP-9 production and blocked cytochalasin A/fMLP-triggered CD62L (L-selectin) shedding, while urolithin A was the ROS inhibitor and urolithin C the elastase inhibitor ^{202Reference 202Piwowarski JP et al. · 2014Influence of gut microbiota-derived ellagitannins’ metabolites urolithins on pro-inflammatory activities of human neutrophils — urolithin A cut stimulated ROS by 42.6–53.7% at 1 µMView study →}.

That converges with the direct rhMMP-9 result ^{212Reference 212Houssein-Zadeh N et al. · 2025Ellagitannins (ellagic acid, urolithin A, urolithin B) inhibit the catalytic activity of human recombinant metalloproteinase 9View study →} into a coherent, B-specific neutrophil and matrix-degradation mechanism.

On the broad cytokine endpoints in the one rigorous head-to-head on human and murine immune cells, urolithin A was the most active metabolite and urolithin B weaker, and none of the glucuronide conjugates had any activity on TNF-α, IL-10 or TGF-β1 ^{213Reference 213Bobowska A et al. · 2021Comparative studies of urolithins and their phase II metabolites on macrophage and neutrophil functionsView study →}; the same held for eicosanoid pathways, where free urolithins at colonic concentrations (1–15 µM) were active while ellagic acid and conjugated urolithins were inactive ^{214Reference 214Giménez-Bastida JA et al. · 2020Inhibition of 5-lipoxygenase-derived leukotrienes and hemiketals as a novel anti-inflammatory mechanism of urolithinsView study →}.

Since conjugates are what circulate at about 100 nM ^{215Reference 215Volpp L et al. · 2020Constituents and metabolites of a French oak wood extract (Robuvit®) in serum and blood cell samples of women undergoing hysterectomyView study →}, the defensible reading is a gut-luminal anti-inflammatory action rather than a systemic one, with the caveat that tissue deconjugation of the glucuronide back to free aglycone is demonstrated at inflamed sites for urolithin A ^{207Reference 207Ávila-Gálvez MÁ et al. · 2019Tissue deconjugation of urolithin A glucuronide to free urolithin A in systemic inflammationView study →} and has not been tested for B.

Vescalagin has two mechanistically separate routes.

Locally, purified vescalagin (with castalagin) inhibited IL-8 release from H. pylori-infected human gastric epithelial cells at IC50 ≈ 11 µM, partly through attenuated NF-κB signalling, a mucosal effect at a concentration the gut can reach ^{30Reference 30Piazza S et al. · 2023Ellagitannins from Castanea sativa Mill. leaf extracts impair H. pylori viability and infection-induced inflammation in human gastric epithelial cellsView study →}.

Systemically, the parent molecule is irrelevant: pure vescalagin incubated with human faecal microbiota is converted to urolithins A, B and C, and it is those metabolites that inhibit TNF-α release from human THP-1-derived macrophages, urolithin A at nanomolar concentrations ^{19Reference 19Piwowarski JP et al. · 2014Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials — ex vivoView study →}.

The systemic anti-inflammatory action therefore belongs to a shared downstream metabolite, is subject to urolithin metabotype variation, and is not specific to vescalagin over any other ellagitannin.

Carried by camu-camu.

Isolated vincamine suppresses NF-κB activation and the downstream cytokine triad TNF-α, IL-6 and IL-1β across unrelated injury models: sepsis-associated liver injury through TNF-α/Nrf-2/Keap-1 ^{216Reference 216Alaaeldin et al. · 2024AnimalVincamine exerts hepato-protective activity during colon-ligation-puncture-induced sepsis by modulating oxidative stress, apoptosis and TNFα/Nrf-2/Keap-1 — animal modelView study →}, ethanol-induced gastric ulcer with reduced mucosal IL-6, IL-1β and TNF-α mRNA ^{217Reference 217Imam et al. · 2025AnimalProtective effects of vincamine against ethanol-induced gastric ulcer by attenuation of IL-6, IL-1β and TNF-α mRNA expression in gastric mucosa of BALB/c mice — animal modelView study →}, gentamicin cardiotoxicity through Nrf2/HO-1–Klotho–pERK/NF-κB crosstalk ^{218Reference 218Abouelhamd et al. · 2026AnimalMechanistic insights into vincamine’s cardio-protection against gentamicin toxicity: crosstalk between Nrf2/HO-1 and related pathways — animal modelView study →}, and Parkinson’s-model neuroinflammation ^{219Reference 219Wang et al. · 2024AnimalVincamine alleviates brain injury by attenuating neuroinflammation and oxidative damage in a mouse model of Parkinson’s disease through NF-κB and Nrf2/HO-1 signalling — animal modelView study →}.

It also engages the NLRP3 inflammasome through a CDK1–glycolysis axis in alcoholic liver injury, a more specific claim than generic NF-κB inhibition ^{220Reference 220Xin et al. · 2026AnimalVincamine attenuates alcoholic liver injury through modulation of a CDK1-glycolysis-NLRP3 immunometabolic axis — animal modelView study →}.

The evidence is preclinical only, for the isolated alkaloid at rodent doses, with no human inflammatory-marker data and no whole-plant preparation anywhere in the set.

Carried by lesser periwinkle.

The pathway assignment is plausible and consistent across two independent materials, but the purified-compound evidence is a single concentration in a single cell line, with no IC₅₀, no dose–response and no animal model, and 20 µM is well above any exposure the molecule has been shown to reach.

The data are isolate data, and no whole-extract effect has been attributed to akuammidine.

Ephedrannin B suppresses NF-κB translocation and p38 MAPK phosphorylation in LPS-stimulated RAW 264.7 macrophages, cutting transcription of TNF-α and IL-1β, the same transcriptional hub that curcumin and most polyphenol anti-inflammatories converge on, reached here by an A-type proanthocyanidin rather than a small phenolic ^{86Reference 86Kim IS et al. · 2010Ephedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators by suppressing nuclear factor-κB activation in RAW 264.7 macrophagesView study →}.

It is the more potent of the two ephedrannins, active at roughly a tenth of ephedrannin A’s optimal concentration ^{86Reference 86Kim IS et al. · 2010Ephedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators by suppressing nuclear factor-κB activation in RAW 264.7 macrophagesView study →}, and the pathway finding reproduces in a second cell type, RSV-infected human bronchial epithelium, where it blunted the IL-6, IL-8, IL-1β and TNF-α response through the same MAPK–NF-κB axis ^{87Reference 87Hou S et al. · 2020Ephedrannin B exerts anti-viral and anti-inflammatory properties in BEAS-2B cells infected with respiratory syncytial virusView study →}.

The limit is exposure.

It is a large, polar, doubly-linked condensed tannin with no pharmacokinetic data at all and an expectation of poor oral absorption, and it has never been given to a living animal in purified form.

The only in-vivo anti-inflammatory data (mouse DSS colitis: colonic TNF-α and IL-6 down, IL-10 up) used a whole root proanthocyanidin extract in which this dimer was only tentatively identified by mass spectrometry ^{88Reference 88Lv M et al. · 2022Rapid screening of proanthocyanidins from the roots of Ephedra sinica Stapf and its preventative effects on dextran-sulfate-sodium-induced ulcerative colitisView study →}.

Carried by ephedra root, not the alkaloid-bearing stem.

The result is for (S)-goitrin rather than epigoitrin.

(S)-Goitrin improved survival, hypothermia and lung damage in LPS-induced septic shock in C57BL/6J mice by inhibiting cleaved caspase-11 and GSDMD-NT, explicitly independent of TLR4, and the finding was confirmed in a poly(I:C)-primed caspase-11-mediated model ^{89Reference 89Ruan D et al. · 2023AnimalThe protective effects of goitrin on LPS-induced septic shock in C57BL/6J mice via caspase-11 non-canonical inflammasome inhibitionView study →}.

That is a well-executed in-vivo result for a named pyroptosis pathway and the strongest anti-inflammatory finding in the goitrin family.

Epigoitrin itself has never been tested in this model, and the mirror image cannot be assumed to behave identically.

It stands as a family mechanism attributed to (S)-goitrin.

Carried by isatis.

Ellagitannin-enriched Rubus extracts inhibited TNF-α-induced NF-κB-driven transcription in gastric AGS cells (IC₅₀ 0.67–1.73 µg/mL) and IL-8 secretion (IC₅₀ 0.7–4 µg/mL), and cut ethanol-induced ulcer index by 75–88% in rats dosed orally at 20 mg/kg/day, with reduced gastric CINC-1 and NF-κB nuclear translocation; sanguiin H-6 and lambertianin C were tested individually and judged responsible at least in part for the mixtures’ activity ^{127Reference 127Sangiovanni E et al. · 2013In vitroEllagitannins from Rubus berries for the control of gastric inflammation — in vitro and in vivo studiesView study →}.

The gastric mucosal surface is the one anti-inflammatory setting a 2,806-Da molecule can reach after swallowing.

The in-vivo arm used extracts rather than the purified trimer, so the molecular attribution is inferential; there is no human study, and no systemic anti-inflammatory action is available to this molecule.

Carried by raspberry leaf.

Perlolyrin’s one good study comes from microbiology rather than phytotherapy.

Lactobacillus crispatus, the keystone species of a healthy vaginal microbiome, produces a family of nine β-carbolines, and perlolyrin (their BC6) was the most anti-inflammatory of the set ^{142Reference 142Glick VJ et al. · 2024Vaginal lactobacilli produce anti-inflammatory β-carboline compounds — [animal] + primary human cellsView study →}.

In primary human cells the compounds suppressed NF-κB and interferon signalling downstream of several pattern-recognition receptors and significantly damped IFNAR activation in monocytes; perlolyrin was enriched in cervicovaginal lavage from people with low Nugent scores versus people with bacterial vaginosis; and topical perlolyrin at 100 µM daily (days 4–8 post-infection) significantly reduced vaginal inflammation in a mouse genital-herpes model ^{142Reference 142Glick VJ et al. · 2024Vaginal lactobacilli produce anti-inflammatory β-carboline compounds — [animal] + primary human cellsView study →}.

It is isolate work from a single group, a single paper, a single anatomical compartment and a topical route.

The exposure ceiling is severe: rat oral 2 mg/kg gives Cmax 18.84 µg/L, about 71 nM ^{143Reference 143Tang GH et al. · 2000AnimalPharmacokinetics of perlolyrine in rats by stable isotope dilution in conjunction with GC-MS — [animal]View study →}, while the cell work runs at 10–100 µM, a 100- to 1,400-fold gap that no herbal or dietary intake closes.

Carried by codonopsis and tribulus.

Protogracillin was reported active in an anti-inflammatory, urate-lowering and anti-diabetic in-vitro panel run on twelve compounds purified to more than 95% from Dioscorea spongiosa, but no IC₅₀, target or dose–response was published for it ^{96Reference 96Wang Z et al. · 2024Efficient discovery of active isolates from Dioscorea spongiosa by the combination of bioassay-guided macroporous resin column chromatography and high-speed counter-current chromatographyView study →}.

A better-controlled study designed to identify Dioscorea nipponica’s anti-inflammatory actives quantified seven saponins including protogracillin and then selected protodioscin, dioscin and gracillin instead, confirming those three against LPS-stimulated RAW264.7 macrophages with NO-inhibition IC₅₀ of 0.712, 0.469 and 0.815 µM and reductions in TNF-α, IL-1β and IL-6; protogracillin was measured and not selected ^{79Reference 79Yang G et al. · 2022Identification of anti-inflammatory components in Dioscorea nipponica Makino based on HPLC-MS/MS, quantitative analysis of multiple components by single marker and chemometric methodsView study →}.

A purified saponin fraction containing protogracillin out-performed the crude extract in the same macrophage model, a fraction result rather than a molecule result ^{97Reference 97Qin Z et al. · 2025Purification of steroidal saponins from Dioscoreae hypoglaucae rhizoma by macroporous resin and evaluation of their anti-inflammatory effectView study →}.

No molecular target has been named for protogracillin, and the mechanism belongs to its spirostanol conversion product, gracillin, until one is published.

Carried by tribulus.

Terrestrosin D suppresses TNF-α, IL-6, IL-8, TGF-β1 and PDGF-AB in bronchoalveolar lavage fluid after bleomycin lung injury, cutting hydroxyproline deposition and Ashcroft fibrosis scores, with TNF-α and TGF-β1 nominated as the therapeutic targets on metabolomic and network analysis ^{188,189Reference 188Qiu M et al. · 2019AnimalTerrestrosin D from Tribulus terrestris attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice — [animal model]View study →Reference 189Yang X et al. · 2022AnimalMechanisms exploration of terrestrosin D on pulmonary fibrosis based on plasma metabolomics and network pharmacology — [animal model]View study →}.

In skin it acts further upstream, blocking substance-P-driven maturation of CD11c⁺ dendritic cells and their release of IL-12p70 and IL-23, a specific and unusual mechanism for a saponin ^{190Reference 190Guo J et al. · 2022AnimalTerrestrosin D ameliorates skin lesions in an imiquimod-induced psoriasis-like murine model by inhibiting the interaction between substance P and dendritic cells — [animal model]View study →}.

Both threads are single-institution, rodent-only, and used the intraperitoneal route, so nothing establishes that an oral dose of tribulus delivers this molecule to lung or skin.

The limit is exposure rather than mechanism quality.

Carried by tribulus.

Tribulusamide D suppresses the classic LPS-induced inflammatory programme in RAW 264.7 macrophages by blocking p38 MAPK phosphorylation (leaving ERK and JNK untouched) and reducing NF-κB nuclear translocation, with downstream loss of iNOS and COX-2 at both mRNA and protein level and correspondingly lower NO, PGE₂, TNF-α and IL-6 ^{191Reference 191Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

Mechanistically it is a conventional catechol-bearing phenolic amide acting on the NF-κB/MAPK hub, the same pathway its structural twin N-trans-p-caffeoyltyramine and most hydroxycinnamoyl amides act on.

The limit is potency.

In the paper that named it, tribulusamide D was the weakest of four active amides from the same extract at IC₅₀ 83.4 µM, against 14.7 µM for N-trans-caffeoyl tyramine, 38.6 µM for terrestriamide and 42.3 µM for N-trans-feruloyl tyramine, with the L-NMMA positive control at 25.3 µM ^{192Reference 192Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}.

It also flattens IL-10, an anti-inflammatory cytokine, alongside the inflammatory ones ^{191,193Reference 191Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →Reference 193Ko HJ et al. · 2015In vitroN-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells — in vitroView study →}, broad suppression rather than selective action.

All of it is one cell line, one laboratory, no animal and no human data, at concentrations (25–100 µM) that straddle its own IC₅₀; it is a minor contributor to a Tribulus amide-fraction effect.

Carried by tribulus.

Vulgarin is the counterexample in the sesquiterpene-lactone anti-inflammatory story.

It lacks the α-methylene-γ-lactone that lets most of the class alkylate cysteine thiols and shut down NF-κB non-selectively; its only electrophile is a ring-A α,β-unsaturated ketone ^{221,222Reference 221PubChem Compound Summary CID 94253 — Vul et al.National Center for Biotechnology InformationView study →Reference 222Paulsen E · 2023ReviewThe sesquiterpene lactone mix: a review of past, present and future aspects — reviewView study →}.

That group is the pharmacophore: vulgarin preferentially inhibits COX-2 over COX-1 (IC50 7.21 vs 11.32 in the source’s stated units, roughly 90-fold weaker than celecoxib in the same run), and reducing the C-1 carbonyl by biotransformation abolishes the COX-2 preference ^{223Reference 223ElGamal RA et al. · 2023In vitroMicrobial transformation of the sesquiterpene lactone, vulgarin, by Aspergillus niger — in vitroView study →}.

In vivo, oral vulgarin and its C-4 epimer at 10–20 mg/kg reduced TNF-α, IL-1β and MDA and downregulated HMGB1 and NF-κB on immunohistochemistry in a rat pancreatic ischaemia–reperfusion model ^{224Reference 224Althurwi HN et al. · 2026AnimalEffect of vulgarin and epivulgarin on ischemia-reperfusion-induced pancreatic injury in rats: a biochemical, molecular, and histopathological evaluation — animal studyView study →}.

It is one in-vivo model from one laboratory group, with an unremarkable COX potency, no human data and no pharmacokinetics; the microbial metabolism data suggest first-pass carbonyl reduction would deactivate the group the activity depends on ^{223,225Reference 223ElGamal RA et al. · 2023In vitroMicrobial transformation of the sesquiterpene lactone, vulgarin, by Aspergillus niger — in vitroView study →Reference 225Orabi KY et al. · 2013In vitroBiotransformation of vulgarin — in vitroView study →}.

The isolate came from Artemisia judaica rather than from mugwort.

Carried by mugwort.