Paeoniflorin

Paeoniflorin at a Glance

Paeoniflorin is the principal monoterpene glucoside of peony root (Paeonia lactiflora) — a structurally distinctive caged pinane-type monoterpenoid (C23H28O11) that serves as the pharmacopoeial marker of both white peony (Bai Shao) and red peony (Chi Shao). It is what quality-control assays measure to certify peony root, and the molecule most peony pharmacology is built around ^{2,15Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}.

Its real-world importance is as the lead component of Total Glucosides of Paeony (TGP) — a standardised root extract (≥40% paeoniflorin) that is an approved anti-rheumatoid and immunomodulatory medicine in China, with genuine randomised-trial evidence in rheumatoid arthritis and other autoimmune conditions ^{1,4Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →}. Beyond the joints, the isolated molecule shows anti-inflammatory, antidepressant, neuroprotective, hepatoprotective and analgesic/antispasmodic activity across cell and rodent models, and it is half of the classic peony–licorice (Shaoyao-Gancao) pairing for muscle cramps ^{6,10,12Reference 6Tang M et al. · 2021AnimalPaeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathwayView study →Reference 10Li X et al. · 2010AnimalPaeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in miceView study →Reference 12Kimura M et al. · 1984AnimalBlocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouseView study →}.

Two caveats run through the whole file. First, most human evidence belongs to the TGP extract, not to purified paeoniflorin — the isolate’s own record is preclinical. Second, paeoniflorin has very low oral bioavailability (roughly 3–4% in rats), which sits awkwardly against the strong in-vitro potencies and is central to how the molecule should be read ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Total Glucosides of Paeony — The Signature Story

The reason paeoniflorin matters clinically is not the pure molecule but the standardised extract it dominates. Total Glucosides of Paeony (TGP) is a water/ethanol extract of white peony root containing more than fifteen glucosides, of which paeoniflorin is the most abundant (≥40%) and the component to which TGP’s effects are chiefly attributed ^{1Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →}. TGP received official authorisation in China as a medication for rheumatoid arthritis, and it is used as an immune-modulating adjunct across several autoimmune diseases ^{1,4Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →}.

Mechanistically, TGP and paeoniflorin behave as bidirectional immunomodulators rather than blunt immunosuppressants: they can dampen an over-active inflammatory response while sparing (or restoring) normal immune function ^{1Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →}. In collagen-induced arthritis the extract suppresses the maturation and activation of dendritic cells, which in turn reduces differentiation of pro-inflammatory Th1 and Th17 cells and lowers IL-17, IL-6 and TNF-α — shifting the Th17/Treg balance back toward tolerance ^{3Reference 3Lin J et al. · 2012Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritisView study →}. This immunological read is the throughline behind the rheumatoid-arthritis, Sjögren’s and other autoimmune applications.

The chemistry sets the terms. Paeoniflorin is a polar, water-soluble glucoside — the sugar and its caged monoterpene aglycone make it hydrophilic and a substrate for intestinal efflux and glucosidase hydrolysis, which is why its oral bioavailability is so low ^{14Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. The practical consequence is that TGP’s clinical dosing runs to grams per day, and that plant/gut context (co-constituents, microbiota) plausibly matters as much as the isolated molecule’s intrinsic potency ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Established Uses

Paeoniflorin’s one genuinely established human role is as the marker and principal active of TGP in rheumatoid arthritis and autoimmune disease — an approved indication in China, supported by randomised trials and systematic reviews ^{1,4Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →}. In this setting TGP is used both as a stand-alone disease-modifying adjunct and, notably, to reduce the liver toxicity of conventional DMARDs: adding TGP to methotrexate-plus-leflunomide in active RA lowered the rate of drug-induced hepatotoxicity without loss of efficacy ^{5Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}.

This is an extract indication, not an isolate one. Everything below the RA/autoimmune application is preclinical for purified paeoniflorin, or belongs to the whole peony root or the peony–licorice combination rather than the pure molecule.

What It's Used For

Paeoniflorin’s pharmacology is broad, mechanistically coherent and unusually well mapped for a plant monoterpene — but the compound-page discipline is decisive here: the human evidence is the TGP extract, while the isolate work is cell and rodent, and the isolate’s low oral bioavailability shadows every in-vitro potency ^{1,2,14Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. The top row’s human weight comes from the TGP extract, not purified paeoniflorin, so read the per-row basis.

01Immunomodulation & Rheumatoid ArthritisPromising62%Approved TGP drug; RA RCTs + systematic reviews; dendritic-cell / Th1-Th17 mechanism ^{1,3,4,5Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 3Lin J et al. · 2012Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritisView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}

02Antidepressant & Anti-AnxietyShaky42%Multiple rodent isolate models; ERK1/2 and ghrelin/GHS-R mechanisms ^{6,7Reference 6Tang M et al. · 2021AnimalPaeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathwayView study →Reference 7Zhang Y et al. · 2021The ghrelin/growth hormone secretagogue receptor system is involved in the rapid and sustained antidepressant-like effect of paeoniflorinView study →}

03Analgesic & AntispasmodicShaky40%Rodent isolate + the peony–licorice synergy; limited human SKT cramp data ^{10,12,13Reference 10Li X et al. · 2010AnimalPaeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in miceView study →Reference 12Kimura M et al. · 1984AnimalBlocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouseView study →Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}

04HepatoprotectiveShaky34%Rodent isolate (liver fibrosis) + TGP as a DMARD hepatotoxicity-sparing adjunct in humans ^{5,10Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →Reference 10Li X et al. · 2010AnimalPaeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in miceView study →}

05Neuroprotective (Alzheimer’s & Parkinson’s)Shaky30%Rodent isolate; adenosine A1, α-synuclein/PKCδ, autophagy ^{8,9Reference 8Kong Y et al. · 2020AnimalPaeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer’s disease via activation of adenosine A1 receptorView study →Reference 9Guo K et al. · 2021AnimalNeuroprotective effect of paeoniflorin in the mouse model of Parkinson’s disease through α-synuclein/protein kinase C δ subtype signaling pathwayView study →}

Mechanisms

The load-bearing point is that paeoniflorin is a many-target immunomodulator, not a single-receptor drug — the immunological (dendritic-cell/Th17) and anti-inflammatory (NF-κB) axes carry the human-relevant RA story, while the CNS mechanisms are preclinical.

Pharmacokinetics

Paeoniflorin’s pharmacokinetics are the crux of the compound page. It is a polar, water-soluble monoterpene glucoside, and its oral bioavailability is very low — on the order of 3–4% in rats ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. The reasons are well characterised: poor intestinal permeability (it lacks lipophilicity), P-glycoprotein-mediated efflux, and hydrolysis by intestinal glucosidases / gut microbiota, which cleave the glucoside before absorption ^{14Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. Once absorbed it is rapidly cleared and widely distributed to heart, liver, spleen, lung, kidney, brain, stomach and intestine, with a short elimination half-life ^{2Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →}.

This profile has two practical consequences the page must flag. (1) In-vitro and injected-dose potencies overstate what an oral dose achieves, so cell-level EC50s should be read cautiously. (2) Co-administration changes exposure — classically, sinomenine and certain “inner-warming” co-herbs raise paeoniflorin bioavailability, and the traditional multi-herb decoction context is not pharmacokinetically neutral ^{14Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. Robust human ADME parameters for the isolate remain thin; most quantitative PK is rodent, and the human “dose” that exists is the TGP extract, not pure paeoniflorin ^{2Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →}.

Clinical Trials

Human evidence splits cleanly by what was tested. TGP (paeoniflorin-dominant extract) has a substantial randomised-trial and systematic-review footprint in rheumatoid arthritis and other autoimmune conditions, and as a hepatotoxicity-sparing DMARD adjunct ^{1,4,5Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}. The peony–licorice combination (SKT) has a small, heterogeneous randomised-trial record for muscle cramps ^{13Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}. There are no controlled efficacy trials of purified paeoniflorin as an isolate — the CNS, hepatic and analgesic isolate data are preclinical.

Last checked: July 2026.

The Peony–Licorice Synergy

One of the most-cited facts about paeoniflorin is not about the molecule alone but about a two-herb pairing. The classical formula Shaoyao-Gancao-Tang (Japanese Shakuyaku-kanzo-to, SKT; product code TJ-68) combines peony root and licorice root in roughly equal parts and is used for acute muscle cramps, spasm and colicky pain.

The pharmacology is genuinely synergistic. In isolated nerve–muscle preparations, paeoniflorin (from peony) and glycyrrhizin (from licorice) together block indirectly-stimulated muscle twitching at concentrations where each alone does nothing, and the effect is strongest near the 1:2 paeoniflorin-to-glycyrrhizin ratio present in the formula ^{12Reference 12Kimura M et al. · 1984AnimalBlocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouseView study →}. This is a real “the combination is more than the sum” result — the mechanistic basis for pairing licorice with peony in the cramp formula.

The human record is modest: a systematic review found SKT had a therapeutic effect on muscle cramps across three randomised trials, but heterogeneity and small numbers precluded meta-analysis ^{13Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}. The caution is the licorice half, not the peony half — chronic or high-dose licorice can cause pseudoaldosteronism and hypokalaemia, so long-term SKT use is not benign (see Toxicity). Peony’s contribution to the pairing is often traced to paeoniflorin’s smooth-muscle-relaxant, antispasmodic activity and adenosine-A1-mediated analgesia ^{1,10Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 10Li X et al. · 2010AnimalPaeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in miceView study →}.

Isolate vs. Plant Studies

This molecule inverts the usual isolate-vs-plant caution in an informative way. The mechanistic and behavioural work is overwhelmingly the isolated molecule in cells and rodents — the ERK1/2 and ghrelin antidepressant studies ^{6,7Reference 6Tang M et al. · 2021AnimalPaeoniflorin ameliorates chronic stress-induced depression-like behavior in mice model by affecting ERK1/2 pathwayView study →Reference 7Zhang Y et al. · 2021The ghrelin/growth hormone secretagogue receptor system is involved in the rapid and sustained antidepressant-like effect of paeoniflorinView study →}, the adenosine-A1 Alzheimer and α-synuclein Parkinson neuroprotection ^{8,9Reference 8Kong Y et al. · 2020AnimalPaeoniflorin exerts neuroprotective effects in a transgenic mouse model of Alzheimer’s disease via activation of adenosine A1 receptorView study →Reference 9Guo K et al. · 2021AnimalNeuroprotective effect of paeoniflorin in the mouse model of Parkinson’s disease through α-synuclein/protein kinase C δ subtype signaling pathwayView study →}, and the IL-13 antifibrotic work ^{10Reference 10Li X et al. · 2010AnimalPaeoniflorin ameliorates schistosomiasis liver fibrosis through regulating IL-13 and its signalling molecules in miceView study →} all test paeoniflorin directly. As a preclinical isolate mechanism base, that is a strength.

But the human efficacy evidence is a standardised extract, not the isolate. TGP — a multi-glucoside preparation in which paeoniflorin is merely the largest single component — carries the rheumatoid-arthritis and autoimmune trial record ^{1,4,5Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}, and the muscle-cramp evidence is for the peony–licorice combination ^{13Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}. The isolate’s very low oral bioavailability makes this gap load-bearing: it is not safe to assume a purified-paeoniflorin pill would reproduce TGP’s clinical effect, because the extract’s other glucosides, the gut-microbiota conversion, and co-herb bioavailability effects are all part of how it works ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Its Role in Plants

In peony, paeoniflorin is a pinane-type monoterpene glucoside built on the caged terpenoid skeleton that gives the Paeonia glucosides their distinctive chemistry, accumulated chiefly in the root ^{2,15Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}. As a defence-associated secondary metabolite it contributes, with the co-occurring galloyl glucosides and tannins, to the astringent, deterrent chemistry of the storage root.

Its accumulation is also chemotype- and processing-dependent, which is why it works as a quality marker: the level and the balance of related glucosides (albiflorin, oxypaeoniflorin, the galloyl esters) differ between white peony root (Bai Shao, bark removed, boiled), red peony root (Chi Shao, unprocessed) and tree-peony bark (Moutan) — the same processing that shifts paeonol between the forms ^{15Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}. This is plant/pharmacognostic biology and should not be read as human pharmacology.

Prevalence in Nature

Paeoniflorin is largely confined to the genus Paeonia (family Paeoniaceae), where it is the dominant monoterpene glucoside of the root. It is the pharmacopoeial marker compound: the Chinese Pharmacopoeia sets a minimum of ≥1.6% in white peony root (Radix Paeoniae Alba, Bai Shao) and ≥1.8% in red peony root (Radix Paeoniae Rubra, Chi Shao) ^{15Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}. Reported content varies with species, white-vs-red processing and grade, and the root carries a family of related glucosides alongside it — the isomer albiflorin, oxypaeoniflorin, and galloyl/benzoyl esters such as 6-O-galloylpaeoniflorin ^{15,16Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →Reference 16Washida K et al. · 2009Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →}.

It occurs across ornamental and medicinal Paeonia species (P. lactiflora, P. veitchii, P. suffruticosa, and others such as P. officinalis, P. emodi and P. anomala), but is not a widespread plant volatile the way many monoterpenes are — outside the peonies it is essentially absent, which is exactly why it functions as a genus marker ^{15Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}.

Major Natural Sources

Source	Plant part	Reported paeoniflorin content
White peony root (Paeonia lactiflora, Bai Shao)	root, bark removed	≥1.6% (pharmacopoeial minimum); ~1.6–5% reported
Red peony root (Paeonia lactiflora / P. veitchii, Chi Shao)	root, unprocessed	≥1.8% (pharmacopoeial minimum); ~1.8–5% reported
Tree peony (Paeonia suffruticosa, Moutan)	root bark	present, generally lower; bark is paeonol-rich

These are percentages of the dried root, and the pharmacopoeial figures are minimums for quality control, not measured averages; actual assays vary with species, processing and grade ^{15Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}.

Discovery & Synthesis

Paeoniflorin was isolated from peony root (Paeonia lactiflora) in the 1960s, and its unusual caged pinane-type monoterpene structure — a bicyclic terpenoid cage bearing a glucose and a benzoyl ester — was elucidated in the early 1970s, work that opened up the chemistry of the whole family of Paeonia monoterpene glucosides ^{2,15Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 15Tan YQ et al. · 2020Efficacy, chemical constituents, and pharmacological actions of Radix Paeoniae Rubra and Radix Paeoniae AlbaView study →}. The first total synthesis of this structurally demanding cage monoterpene is a landmark of natural-product synthesis but is not confidently datable from the sources verified here, so it is left uncharacterised rather than mis-cited.

Manufacture today is overwhelmingly by extraction from peony root, not synthesis: paeoniflorin is obtained as the marker of standardised white-peony-root preparations, and Total Glucosides of Paeony — the clinically used product — is a water/ethanol root extract standardised to ≥40% paeoniflorin, not a synthetic active ^{1Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →}. Its polar glucoside structure and low oral bioavailability mean the commercial interest is in the extract and in bioavailability-enhancing formulation/co-administration, rather than in a purified synthetic drug ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Patents: not yet researched.

Toxicity & Safety

Paeoniflorin carries a low toxicity flag. It is the marker of a food-and-medicine root with a long record of use, TGP’s authorised RA indication is explicitly noted for its absence of unacceptable adverse reactions, and the molecule’s own hazard is limited by how little of an oral dose is even absorbed ^{1,14Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. The caveats below are mostly about context — the extract, the co-herb, and the thinness of isolate-specific human safety data.

Safety at a Glance

✅ Low / no toxicity

• Low intrinsic toxicity, favourable clinical safety. TGP (paeoniflorin-dominant) is an approved RA drug noted for good tolerability, and the isolate’s very low oral bioavailability limits systemic exposure ^{1,14Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.
• Immunomodulatory, not broadly immunosuppressive. The dendritic-cell/Th17 effect is bidirectional — it rebalances rather than globally suppresses immunity in the models studied ^{1,3Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 3Lin J et al. · 2012Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritisView study →}.
• The peony–licorice caution is the licorice, not the peony. Chronic or high-dose Shaoyao-Gancao / SKT can cause pseudoaldosteronism and hypokalaemia from the glycyrrhizin half — monitor with prolonged use ^{13Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}.
• Human safety data are for the extract. Controlled tolerability data belong to TGP; dedicated long-term safety, interaction and reproductive datasets for isolated paeoniflorin are limited.
• As an immunomodulator, plausibility of interaction with immune-active drugs. Not well quantified for the isolate; relevant where TGP is combined with DMARDs/immunosuppressants (though the methotrexate-adjunct data are favourable) ^{5Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}.

Full Safety & Interactions Detail

Clinical tolerability (the extract). In rheumatoid-arthritis and autoimmune use, TGP is repeatedly characterised as effective without unacceptable adverse reactions; the most commonly noted effects are mild and gastrointestinal (loose stools/diarrhoea) ^{1,4Reference 1He DY · 2011Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicineView study →Reference 4Luo J et al. · 2019Systematic reviewBenefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviewsView study →}. Adding TGP to methotrexate + leflunomide reduced the DMARD combination’s hepatotoxicity in active RA — a safety benefit in that specific setting ^{5Reference 5Xiang N et al. · 2015Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritisView study →}.

The peony–licorice combination. The pharmacologically important interaction on this molecule’s page is the synergy with licorice glycyrrhizin at the neuromuscular junction, which is therapeutic (the cramp formula) but comes with the licorice-side risk: glycyrrhizin can cause pseudoaldosteronism, sodium/water retention, hypertension and hypokalaemia, so long-term SKT use warrants electrolyte awareness — the risk tracks the licorice half, not paeoniflorin ^{12,13Reference 12Kimura M et al. · 1984AnimalBlocking effects of blended paeoniflorin or its related compounds with glycyrrhizin on neuromuscular junctions in frog and mouseView study →Reference 13Ota K et al. · 2020Clinical trialEffect of Shakuyaku-kanzo-to in patients with muscle cramps: a systematic literature reviewView study →}.

Bioavailability as a safety modifier. The same poor oral absorption that limits efficacy also limits systemic toxicity of the isolate; conversely, co-administration that raises paeoniflorin bioavailability (e.g. sinomenine, certain co-herbs) changes exposure and should be considered when peony is combined in multi-herb formulas ^{14Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}.

Reproductive note (prose only). Peony root is traditionally used in gynaecology, and dedicated reproductive-toxicity data for isolated paeoniflorin are limited; pregnancy and lactation decisions belong to the herb or product page where intake is decided, not to this molecule page. No comprehensive isolate genotoxicity or repeat-dose package is characterised here beyond the extract-level tolerability above.

Dosage

There is no established dose for isolated paeoniflorin. Human dosing is of the standardised extract, Total Glucosides of Paeony (TGP), in which paeoniflorin is the principal component (≥40%):

Isolate figures cited in the research above are preclinical rodent doses and are not convertible to human self-dosing — and the low oral bioavailability of the pure molecule is exactly why the clinically used product is the gram-scale extract, not a purified-paeoniflorin pill ^{2,14Reference 2Zhou YX et al. · 2020ReviewA review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effectsView study →Reference 14Liu ZQ et al. · 2006Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and interactions with sinomenineView study →}. These are doses studied in research and are not a personal recommendation.

References

1. He DY, Dai SM (2011). Anti-inflammatory and immunomodulatory effects of Paeonia lactiflora Pall., a traditional Chinese herbal medicine. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/21687505/
2. Zhou YX, Gong XH, Zhang H, Peng C (2020). A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/32682112/
3. Lin J, et al. (2012). Total glucosides of paeony inhibits Th1/Th17 cells via decreasing dendritic cells activation in rheumatoid arthritis. Cellular Immunology. https://pubmed.ncbi.nlm.nih.gov/23399842/
4. Luo J, et al. (2019). Benefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: an overview of systematic reviews. Chinese Journal of Integrative Medicine. https://pubmed.ncbi.nlm.nih.gov/31385219/
5. Xiang N, et al. (2015). Total glucosides of paeony can reduce the hepatotoxicity caused by methotrexate and leflunomide combination treatment of active rheumatoid arthritis. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/26292180/
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