Skimmianine

Skimmianine at a Glance

Skimmianine is a furoquinoline alkaloid — a quinoline ring fused to a furan, carrying three methoxy groups — and one of the signature molecules of the citrus family, the Rutaceae. It occurs across Zanthoxylum, Ruta, Aegle and Toddalia, and takes its name from Skimmia, the ornamental shrub it was first drawn from.

Its interest is that a single isolated alkaloid reproduces a whole herb’s headline effect. Given at 5 mg/kg to rats with carrageenan-induced paw inflammation, skimmianine cut TNF-α and IL-6 messenger RNA, prostaglandin E2, and the activity of both COX-2 and 5-lipoxygenase — the full eicosanoid axis rather than one arm of it ^{1Reference 1Ratheesh M et al. · 2013AnimalAnti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L. — animal modelView study →}. The mechanism was later traced to NF-κB: in activated microglia it blocks p65 and IκBα phosphorylation and stops NF-κB binding its consensus sites on DNA ^{2Reference 2Ogunrinade FA et al. · 2023In vitroNeuroprotection by skimmianine in lipopolysaccharide-activated BV-2 microglia — in vitroView study →}.

The same ring system that makes it interesting also makes it a photosensitiser, though a much milder one than the furanocoumarins it shares rue with ^{12Reference 12Schimmer O · 1990In vitroMutagenic compounds in an extract from Rutae Herba (Ruta graveolens L.)View study →}. There are no human studies of any kind.

Why It Photosensitises Less Than Rue’s Furanocoumarins

Rue is the plant most people meet skimmianine in, and rue’s reputation is for blistering, sunlight-triggered burns. That reputation belongs mainly to the furanocoumarins — bergapten, xanthotoxin, psoralen — and the difference between them and the furoquinolines is worth stating precisely, because it is structural rather than a matter of degree.

Both classes are planar tricyclics that slide between DNA base pairs and react when UV-A hits them. But a psoralen has two photoreactive double bonds, one on the furan ring and one on the pyrone, so it can react twice — first forming a monoadduct, then, on absorbing a second photon, a crosslink between the two strands. A furoquinoline has only the furan double bond available, so it stops at the monoadduct ^{12Reference 12Schimmer O · 1990In vitroMutagenic compounds in an extract from Rutae Herba (Ruta graveolens L.)View study →}.

That single-versus-double distinction shows up directly in the biology. Testing a commercial rue tincture against a Chlamydomonas mutagenicity strain, Schimmer and Kühne found every constituent photomutagenic, but the most active furoquinoline — dictamnine, not skimmianine — reached only about a tenth of bergapten’s potency, and the authors attributed the gap to exactly this monoadduct-versus-biadduct difference ^{12Reference 12Schimmer O · 1990In vitroMutagenic compounds in an extract from Rutae Herba (Ruta graveolens L.)View study →}. A parallel assay using restriction enzymes as a readout put skimmianine last among the furoquinolines tested for photo-activated DNA binding, behind kokusaginine and haplopine, and its photo-activated antibacterial activity ranked in the same order ^{13Reference 13Hanawa F et al. · 2004In vitroPhoto-activated DNA binding and antimicrobial activities of furoquinoline and pyranoquinolone alkaloids from Rutaceae — in vitroView study →}.

So skimmianine is genuinely light-activated and genuinely DNA-binding, and neither fact should be waved away. It is simply not the molecule doing most of the damage in a rue burn.

What It's Used For

The evidence is entirely preclinical and heavily weighted toward inflammation, where the same NF-κB mechanism keeps reappearing in different tissues. Most of it has arrived since 2020.

Mechanisms

Pharmacokinetics

The load-bearing gap. No human pharmacokinetic data exist, and the one animal study is a metabolite map rather than an exposure measurement: after oral dosing in rats, UPLC/Q-TOF-MS found sixteen metabolites across plasma, urine and faeces, and the dominant routes were epoxidation of the 2,3-double bond on the furan ring followed by hydrolysis of that epoxide, plus O-demethylation and didemethylation, with glucuronide and sulfate conjugates downstream ^{11Reference 11Huang A et al. · 2017AnimalMetabolic profile of skimmianine in rats determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry — animal modelView study →}.

Two things follow. First, skimmianine is extensively metabolised, so the parent compound is unlikely to persist at the concentrations used in cell work. Second, the major transformation is epoxidation of the same furan double bond that carries its photochemistry and its DNA reactivity — a reactive intermediate, and the obvious thing to look at if a toxicology package is ever built. A 2025 paper reports “excellent oral bioavailability” for skimmianine ^{8Reference 8Lv Y et al. · 2025AnimalSkimmianine attenuates osteoclast activity by suppressing ERp57-driven calcium oscillations/calcineurin/Nfatc1 signalling in postmenopausal osteoporosis — animal modelView study →}, but that is a prediction from structure-based software, not a measured figure, and should not be quoted as one.

Clinical Trials

None. There are no clinical trials of skimmianine for any indication, and no human exposure data beyond incidental dietary and medicinal contact with the plants that carry it.

Last checked: September 2026.

Isolate vs. Plant Studies

Unusually for a plant constituent, almost all of the evidence is isolate work — purified skimmianine, dosed or applied on its own ^{1,2,5,6,7,8,9,10Reference 1Ratheesh M et al. · 2013AnimalAnti-inflammatory effect of quinoline alkaloid skimmianine isolated from Ruta graveolens L. — animal modelView study →Reference 2Ogunrinade FA et al. · 2023In vitroNeuroprotection by skimmianine in lipopolysaccharide-activated BV-2 microglia — in vitroView study →Reference 5Korak T et al. · 2025AnimalSkimmianine modulates tumor proliferation and immune dynamics in breast cancer by targeting PCNA and TNF-α — animal modelView study →Reference 6Liu Y et al. · 2022In vitroSkimmianine as a novel therapeutic agent suppresses proliferation and migration of human esophageal squamous cell carcinoma via blocking the activation of ERK1/2 — in vitro and miceView study →Reference 7Huo CL et al. · 2023AnimalSkimmianine attenuates liver ischemia/reperfusion injury by regulating PI3K-AKT signaling pathway-mediated inflammation, apoptosis and oxidative stress — animal modelView study →Reference 8Lv Y et al. · 2025AnimalSkimmianine attenuates osteoclast activity by suppressing ERp57-driven calcium oscillations/calcineurin/Nfatc1 signalling in postmenopausal osteoporosis — animal modelView study →Reference 9Yoshita M et al. · 2024In vitroHigh-throughput screening of antiviral compounds using a recombinant hepatitis B virus and identification of a possible infection inhibitor, skimmianine — in vitroView study →Reference 10Dofuor AK et al. · 2020In vitroIsolation and antitrypanosomal characterization of furoquinoline and oxylipin from Zanthoxylum zanthoxyloides — in vitroView study →}. That is a methodological strength, and it is what makes the molecule a subject in its own right rather than a footnote to rue.

The weakness sits on the other side of the ledger. Because the isolate studies use intraperitoneal injection in rodents or micromolar concentrations in culture, none of them says anything about what a person taking a Rutaceae plant is exposed to. Rue itself is a low-dose, internally-discouraged herb; bael is used as a fruit and an astringent, with its alkaloids in the leaf and root rather than the pulp. The one place the isolate and the plant were compared directly cuts against the molecule: whole rue extract outperformed an equivalent concentration of its own rutin on iNOS and COX-2 suppression, which is the finding that established rue’s activity as additive across constituents rather than resident in any one of them.

A single study has tested skimmianine in combination — with betulinic acid and apigenin, in high-cholesterol-fed rabbits, acting on CD36–TLR2 signalling ^{15Reference 15Sabu V et al. · 2021AnimalSynergistic effect of betulinic acid, apigenin and skimmianine (BASk) in high cholesterol diet rabbit: involvement of CD36-TLR2 signaling pathway — animal modelView study →} — and its results belong to the mixture, not to this molecule.

Prevalence in Nature

Skimmianine is a Rutaceae compound and, within that family, an unusually widespread one. The 2023 review places it as “a major component available in medicinal plants of the family Rutaceae,” with the genus Zanthoxylum — the prickly ashes and Sichuan peppers — as its most consistent home ^{3Reference 3Son NT · 2023ReviewSkimmianine: natural occurrence, biosynthesis, synthesis, pharmacology and pharmacokinetics — reviewView study →}. It is also reported through Toddalia asiatica, Vepris, Glycosmis, Aegle marmelos (bael) and Ruta (rue); in bael the alkaloid fraction, skimmianine included, sits in the leaves and roots rather than the fruit.

Quantified figures for the molecule itself are scarce, so no per-source comparison can be drawn. The best available numbers are fraction-level and from tissue culture rather than field material: Ruta chalepensis grown in temporary-immersion bioreactors accumulated up to 449 mg per 100 g dry weight of total furoquinoline alkaloids — γ-fagarine, 7-isopentenyloxy-γ-fagarine and skimmianine together — against 1,170 mg/100 g of linear furanocoumarins in the same biomass ^{14Reference 14Szewczyk A et al. · 2023In vitroRuta chalepensis L. in vitro cultures as a source of bioactive furanocoumarins and furoquinoline alkaloids — in vitroView study →}. Even in rue, in other words, the furanocoumarins outweigh the furoquinolines.

Within rue there is also a part split that matters for anyone reading a phytochemical list: the acridone alkaloids concentrate in the roots and the furanocoumarins in the aerial parts, and skimmianine’s own distribution follows the alkaloid pattern rather than the coumarin one.

Discovery & Synthesis

The name records the source: skimmianine was obtained from Skimmia, the Rutaceae shrub, and named for it. The original isolation report predates the indexed literature and could not be verified, so no date or discoverer is given here rather than a guessed one. It has also travelled under two other names in the older literature — β-fagarine and chloroxylonine — both of which turn out to be the same molecule, which is worth knowing when reading old phytochemistry.

Biosynthetically it starts from anthranilic acid, the standard entry point to the quinoline alkaloids, with the furan ring and the three methoxy groups added downstream ^{3Reference 3Son NT · 2023ReviewSkimmianine: natural occurrence, biosynthesis, synthesis, pharmacology and pharmacokinetics — reviewView study →}. Laboratory synthesis is short and begins from 2,4,7,8-tetramethoxyquinoline ^{3Reference 3Son NT · 2023ReviewSkimmianine: natural occurrence, biosynthesis, synthesis, pharmacology and pharmacokinetics — reviewView study →}. Nobody manufactures it at scale: supply is analytical-standard quantities isolated from Zanthoxylum or rue, or made to order.

Patents: not yet researched (future patent-loop pass).

Dosage

There is no human dose. The figures below are the research doses behind the sections above, recorded so that the scale is visible, and they are not convertible into an amount a person could take.

Every efficacy dose in the table was given by injection, which bypasses the absorption and first-pass metabolism that would decide an oral figure — and the rat metabolite work shows that metabolism is extensive ^{11Reference 11Huang A et al. · 2017AnimalMetabolic profile of skimmianine in rats determined by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry — animal modelView study →}. These are doses studied in research and are not a personal recommendation.