Oroxylin A

Oroxylin A at a Glance

Oroxylin A is a naturally occurring methoxylated flavone — 5,7-dihydroxy-6-methoxyflavone, i.e. baicalein with a methyl group added at the 6-position (baicalein 6-methyl ether). It is a characteristic constituent of Chinese skullcap (Huang Qin) root, occurs in American skullcap aerial parts, and is the compound the tree Oroxylum indicum was named after.

Its research profile is that of a pro-apoptotic, anti-inflammatory and neuroprotective flavone: most of the literature is preclinical work on cancer-cell metabolism, inflammatory signalling and brain injury. Two things set it apart from its skullcap siblings. First, unlike the sedative flavone wogonin — a positive modulator at the GABA-A benzodiazepine site — oroxylin A is a negative GABA-A modulator, and in animals it is pro-cognitive rather than calming (its own named section below). Second, it is one of the few skullcap flavones to have crossed from bench pharmacology into formal drug development, completing a Phase I safety and pharmacokinetics trial as an isolated tablet.

As with the rest of the family, the honest headline is that the human evidence so far is a safety/PK study, not an efficacy trial — the therapeutic claims remain preclinical, and almost all of them test the isolated molecule rather than whole skullcap.

Oroxylin A vs. Wogonin: A Negative GABA-A Modulator

This is the most distinctive thing about the molecule and the reason it earns its own page. The Scutellaria flavones are often lumped together as “calming skullcap compounds,” but oroxylin A and wogonin pull the GABA-A receptor in opposite directions.

Wogonin is a positive modulator. It binds the benzodiazepine site of the GABA-A receptor and enhances GABAergic inhibition, producing an anxiolytic effect that is blocked by the benzodiazepine antagonist flumazenil (Ro15-1788) — a classic positive-allosteric-modulator signature ^{3Reference 3Hui KM et al. · 2002Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis GeorgiView study →}.

Oroxylin A does the reverse. In mice it reverses scopolamine- and diazepam-induced amnesia, improving performance on passive-avoidance, Y-maze and Morris-water-maze tasks; crucially, its pro-cognitive effect is antagonised by the GABA-A agonists muscimol and diazepam, and at the cellular level oroxylin A inhibits the GABA-induced inward chloride current in single cortical neurons ^{1Reference 1Kim DH et al. · 2007AnimalThe ameliorating effect of oroxylin A on scopolamine-induced memory impairment in miceView study →}. In other words it behaves as a GABA-A antagonist / negative modulator — dialling down inhibitory tone rather than up. A separate study found it also facilitates memory consolidation, raising mature BDNF in the hippocampus after training ^{2Reference 2Kim DH et al. · 2014AnimalOroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in miceView study →}.

The practical upshot: within one plant, wogonin trends sedative/anxiolytic and oroxylin A trends pro-cognitive/anti-amnesic, and a whole-root extract carries both. This is a preclinical, rodent-level distinction — there is no human cognition trial of isolated oroxylin A — but it is a clean mechanistic contrast, and it is why oroxylin A is discussed as a nootropic-leaning flavone while wogonin is discussed as a calming one.

Clinical Development Status

Oroxylin A is unusual among plant flavones in having entered formal clinical development as an isolated drug candidate. A Phase I, double-blind, placebo-controlled trial in Chinese healthy volunteers tested oroxylin A tablets across single ascending doses (400, 800, 1,600 and 2,400 mg), multiple doses (1,600 or 2,400 mg once daily for 10 days) and a food-effect arm ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}.

The trial was a safety and pharmacokinetics study, not an efficacy trial: it reported no dose-limiting toxicities, serious adverse events or deaths, with gastrointestinal adverse events more common on repeat dosing; oroxylin A appeared rapidly in plasma, Cmax rose roughly dose-proportionally while AUC rose less than dose-proportionally (a hint of saturable absorption), a high-fat meal raised Cmax ~1.6-fold, and the profile supported once-daily, after-meals dosing in future studies ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}. It is being developed chiefly on the strength of its antitumor preclinical record.

This matters for reading everything below: the compound has a clean early human safety signal, but its disease claims are still preclinical.

What It's Used For

Oroxylin A’s pharmacology is broad and mechanistically interesting, but the evidence base is preclinical and dominated by the isolated molecule — cell lines and rodent models — with the only human data being the Phase I safety/PK study above ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView 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. There is a completed human safety/PK trial but no efficacy trial, so every application below rests on preclinical data and scores accordingly.

01Anticancer / pro-apoptotic (metabolic reprogramming, SIRT3)Shaky40%Large preclinical set; SIRT3, glycolytic-kinase / HIF-1α remodelling ^{6,7,8Reference 6Lee CW et al. · 2026SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancerView study →Reference 7Wang P et al. · 2023Oroxylin A promoted apoptotic extracellular vesicles transfer of glycolytic kinases to remodel immune microenvironment in hepatocellular carcinoma modelView study →Reference 8Liu X et al. · 2025Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathwayView study →}

02Pro-cognitive / anti-amnesic (GABA-A negative modulation)Shaky36%Rodent isolate; GABA-A antagonism + BDNF-linked consolidation ^{1,2Reference 1Kim DH et al. · 2007AnimalThe ameliorating effect of oroxylin A on scopolamine-induced memory impairment in miceView study →Reference 2Kim DH et al. · 2014AnimalOroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in miceView study →}

03Anti-inflammatory (NLRP3 inflammasome)Shaky30%Colitis + cellular models; NLRP3, SIRT3-SOD2 ^{9,8Reference 9Zhou W et al. · 2017Oroxylin A inhibits colitis by inactivating NLRP3 inflammasomeView study →Reference 8Liu X et al. · 2025Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathwayView study →}

04Neuroprotective (brain bioenergetics)Shaky26%Post-stroke rodent model; CDK9/p53/VDAC, ATP support ^{10Reference 10Xia J et al. · 2024Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomesView study →}

05Hepatoprotective / anti-fibroticShaky22%Oroxylin-A-specific liver-fibrosis review; preclinical mechanisms ^{13Reference 13Wang S et al. · 2025Deciphering the role of oroxylin A in liver fibrosisView study →}

Mechanisms

The load-bearing points are two: the negative GABA-A modulation (the wogonin contrast, and the pro-cognitive signal), and SIRT3 as a shared node linking the anticancer, anti-inflammatory and antioxidant effects.

Pharmacokinetics

The Phase I trial gives the clearest human picture: oral oroxylin A tablets are rapidly absorbed (tmax ≈ 0.17–5.0 h), Cmax rises roughly dose-proportionally while AUC rises less than dose-proportionally — consistent with saturable absorption at higher doses — with moderate accumulation (~1.5–1.7-fold) over 10 days of once-daily dosing and a positive food effect (a high-fat meal raised Cmax ~1.6-fold), hence the recommendation to dose after meals ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}. Like other skullcap flavones, oroxylin A undergoes extensive phase-II metabolism — in-vitro/in-vivo metabolite work identifies glucuronide and other conjugates as major species across test systems ^{5Reference 5Bian Y et al. · 2022In vitroMetabolites identification and species comparison of oroxylin A, an anti-cancer flavonoid, in vitro and in vivo by HPLC-Q-TOF-MS/MSView study →}, and in a whole-extract bioavailability model oroxylin A and its glucuronide were the only skullcap bioactives able to cross the Caco-2 intestinal barrier and an artificial lipid membrane, respectively ^{12Reference 12Buccato DG et al. · 2024In vitroIn vitro assessment of cortisol release inhibition, bioaccessibility and bioavailability of a chemically characterized Scutellaria lateriflora L. hydroethanolic extractView study →}. That conjugation-heavy disposition is the usual reason flavone plasma levels stay modest and why in-vitro potencies do not translate one-to-one to systemic exposure.

Clinical Trials

Human evidence is limited to one completed Phase I safety/PK study in healthy volunteers of pharmaceutical-grade oroxylin A tablets ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →} (trial registration ChiCTR2100051434). There are no completed efficacy trials in any indication; the disease rationale (chiefly oncology) rests on preclinical work.

Last checked: July 2026.

Isolate vs. Plant Studies

Oroxylin A’s evidence is overwhelmingly the isolated molecule — a strength for mechanistic clarity, a limit for whole-herb translation. The cancer-metabolism, GABA-A, NLRP3 and stroke studies all test purified oroxylin A (or, in the lung-cancer work, a synthetic phosphate-ester derivative ^{6Reference 6Lee CW et al. · 2026SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancerView study →}) in cells or rodents ^{1,2,7,8,9,10Reference 1Kim DH et al. · 2007AnimalThe ameliorating effect of oroxylin A on scopolamine-induced memory impairment in miceView study →Reference 2Kim DH et al. · 2014AnimalOroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in miceView study →Reference 7Wang P et al. · 2023Oroxylin A promoted apoptotic extracellular vesicles transfer of glycolytic kinases to remodel immune microenvironment in hepatocellular carcinoma modelView study →Reference 8Liu X et al. · 2025Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathwayView study →Reference 9Zhou W et al. · 2017Oroxylin A inhibits colitis by inactivating NLRP3 inflammasomeView study →Reference 10Xia J et al. · 2024Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomesView study →}, and the Phase I trial dosed a purified tablet ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}. Whole-plant context appears in two places: the Oroxylum indicum chemobrain study used a plant extract ^{11Reference 11Pondugula SR et al. · 2021Oroxylum indicum ameliorates chemotherapy induced cognitive impairmentView study →}, and a whole S. lateriflora extract bioavailability model is where oroxylin A stood out as one of the few constituents to actually cross the gut barrier ^{12Reference 12Buccato DG et al. · 2024In vitroIn vitro assessment of cortisol release inhibition, bioaccessibility and bioavailability of a chemically characterized Scutellaria lateriflora L. hydroethanolic extractView study →}. In skullcap, oroxylin A is a minor flavone taken alongside far larger amounts of baicalin, baicalein and wogonin — so a real-world skullcap dose delivers little isolated oroxylin A, and the whole-root effect is a blend (including wogonin’s opposite, sedative GABA-A action).

Its Role in Plants

In Scutellaria and Oroxylum, oroxylin A belongs to the family’s characteristic flavone chemistry. It is biosynthetically a methylated derivative of baicalein — the 6-methyl ether — placing it downstream of the same free-B-ring flavone pathway that yields baicalein, baicalin, scutellarein and wogonin from the root. These flavones function largely as defence and antioxidant compounds for the plant; oroxylin A itself is a minor member of that mixture rather than a dominant one. As always, a molecule’s role in the plant does not predict its pharmacology in people.

Prevalence in Nature

Oroxylin A is not a widespread plant volatile but a taxonomically narrow flavone, concentrated in two lineages:

• Skullcaps (Scutellaria). It is a minor root flavone of Chinese skullcap (S. baicalensis, Huang Qin), where it accompanies the far more abundant baicalin (roughly 8–12% of the dried root), baicalein (~5%) and wogonin (~1.3%) ^{14Reference 14Nguyen HL et al. · 2025Systematic reviewA systematic review of evidence-based health benefits of Oroxylum indicum and its functional food potentialView study →}. It also occurs in American skullcap (S. lateriflora) aerial parts, notable there as one of the few constituents demonstrably absorbable across the gut barrier ^{12Reference 12Buccato DG et al. · 2024In vitroIn vitro assessment of cortisol release inhibition, bioaccessibility and bioavailability of a chemically characterized Scutellaria lateriflora L. hydroethanolic extractView study →}.
• Indian trumpet tree (Oroxylum indicum). The compound is named after this species and appears across its ethnopharmacology and functional-food literature ^{11,14Reference 11Pondugula SR et al. · 2021Oroxylum indicum ameliorates chemotherapy induced cognitive impairmentView study →Reference 14Nguyen HL et al. · 2025Systematic reviewA systematic review of evidence-based health benefits of Oroxylum indicum and its functional food potentialView study →}.

Precise percentage figures for oroxylin A specifically are not well quantified in the sources reviewed here — it is consistently described qualitatively as a minor skullcap flavone rather than given a dry-weight range (logged in this compound’s gaps tracker to chase).

Discovery & Synthesis

Oroxylin A takes its name from Oroxylum indicum, the tree from which flavones of this type were characterised, and it has long been recognised as a constituent of Scutellaria baicalensis root, one of the most-used herbs in traditional Chinese medicine ^{1,14Reference 1Kim DH et al. · 2007AnimalThe ameliorating effect of oroxylin A on scopolamine-induced memory impairment in miceView study →Reference 14Nguyen HL et al. · 2025Systematic reviewA systematic review of evidence-based health benefits of Oroxylum indicum and its functional food potentialView study →}. Structurally it is simply baicalein (5,6,7-trihydroxyflavone) methylated at the 6-position — 5,7-dihydroxy-6-methoxyflavone — so it can be obtained either by extraction from skullcap root or by selective methylation of baicalein. Its most recent chapter is pharmaceutical: purified oroxylin A tablets have been manufactured to drug-grade for the Phase I trial, and medicinal chemists have made semi-synthetic derivatives (e.g. the phosphate-ester prodrug used in the lung-cancer work) to improve its druglike properties ^{4,6Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →Reference 6Lee CW et al. · 2026SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancerView study →}.

Patents: not yet researched.

Toxicity & Safety

Oroxylin A carries a low flag: the completed Phase I trial reported no dose-limiting toxicities, serious adverse events or deaths across single doses up to 2,400 mg and 10-day repeat dosing, with the main finding being more frequent gastrointestinal adverse events on multiple dosing ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}. That is a clean early human safety signal for an isolated flavone. The caveats are about context, not acute hazard.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• Clean Phase I safety signal. No dose-limiting toxicities, serious adverse events or deaths in healthy volunteers up to 2,400 mg single and 2,400 mg/day repeat dosing; main effect was mild-to-moderate GI upset on multiple dosing ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}.
• CNS-active in an excitatory direction. As a negative GABA-A modulator it lowers inhibitory tone (that is how it aids cognition in rodents) — so at high isolated doses the theoretical concern is over-excitation, and it should not be assumed to be sedative like the rest of skullcap ^{1Reference 1Kim DH et al. · 2007AnimalThe ameliorating effect of oroxylin A on scopolamine-induced memory impairment in miceView study →}.
• Pro-apoptotic / metabolism-altering by design. Its anticancer mechanisms (SIRT3, glycolysis, mitochondrial) are potent cellular actions; the consequences of chronic high-dose isolated exposure in healthy tissue are not established beyond the short Phase I window ^{6,8Reference 6Lee CW et al. · 2026SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancerView study →Reference 8Liu X et al. · 2025Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathwayView study →}.
• Interaction scope not characterised. Flavones of this family modulate drug-metabolising enzymes and transporters; specific CYP/UGT/transporter interaction data for isolated oroxylin A were not assessed here — absence of data is not evidence of safety.

Pregnancy/lactation is a per-herb / per-supplement decision and is not adjudicated on this molecule page; dedicated human reproductive data for isolated oroxylin A are lacking, and no isolate-specific verdict is issued here.

Dosage

There is no established dietary or supplement dose for isolated oroxylin A. The only human figures are research doses from the Phase I trial of pharmaceutical-grade tablets ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}:

These were administered under medical supervision to characterise safety and pharmacokinetics, and the data supported once-daily, after-meals dosing in future studies ^{4Reference 4Yang F et al. · 2026RCTSafety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect studyView study →}. Herbal exposure is indirect and much smaller — oroxylin A is a minor flavone within a whole skullcap-root dose, taken alongside larger amounts of baicalin, baicalein and wogonin, not as an isolate. These are research figures, not a personal recommendation.

References

1. Kim DH, et al. (2007). The ameliorating effect of oroxylin A on scopolamine-induced memory impairment in mice. Neurobiology of Learning and Memory. https://pubmed.ncbi.nlm.nih.gov/17196405/
2. Kim DH, et al. (2014). Oroxylin A enhances memory consolidation through the brain-derived neurotrophic factor in mice. Brain Research Bulletin. https://pubmed.ncbi.nlm.nih.gov/25218897/
3. Hui KM, et al. (2002). Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochemical Pharmacology. https://pubmed.ncbi.nlm.nih.gov/12392823/
4. Yang F, et al. (2026). Safety and pharmacokinetics evaluation of oroxylin A in Chinese healthy volunteers: a phase I, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect study. Clinical & Translational Oncology. https://pubmed.ncbi.nlm.nih.gov/40903694/
5. Bian Y, et al. (2022). Metabolites identification and species comparison of oroxylin A, an anti-cancer flavonoid, in vitro and in vivo by HPLC-Q-TOF-MS/MS. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/35345974/
6. Lee CW, et al. (2026). SIRT3 activation by oroxylin A phosphate diethyl ester triggers mitochondrial dysfunction and apoptosis in non-small cell lung cancer. International Journal of Biological Sciences. https://pubmed.ncbi.nlm.nih.gov/42212315/
7. Wang P, et al. (2023). Oroxylin A promoted apoptotic extracellular vesicles transfer of glycolytic kinases to remodel immune microenvironment in hepatocellular carcinoma model. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/37660969/
8. Liu X, et al. (2025). Oroxylin A alleviates pyroptosis and apoptosis in human corneal epithelial cells under hyperosmotic stress by activating the SIRT3-SOD2/HIF-1α pathway. Experimental Eye Research. https://pubmed.ncbi.nlm.nih.gov/40096905/
9. Zhou W, et al. (2017). Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome. Oncotarget. https://pubmed.ncbi.nlm.nih.gov/28938606/
10. Xia J, et al. (2024). Suppression of neuronal CDK9/p53/VDAC signaling provides bioenergetic support and improves post-stroke neuropsychiatric outcomes. Cellular and Molecular Life Sciences. https://pubmed.ncbi.nlm.nih.gov/39235466/
11. Pondugula SR, et al. (2021). Oroxylum indicum ameliorates chemotherapy induced cognitive impairment. PLoS One. https://pubmed.ncbi.nlm.nih.gov/34081735/
12. Buccato DG, et al. (2024). In vitro assessment of cortisol release inhibition, bioaccessibility and bioavailability of a chemically characterized Scutellaria lateriflora L. hydroethanolic extract. Molecules. https://pubmed.ncbi.nlm.nih.gov/38338331/
13. Wang S, et al. (2025). Deciphering the role of oroxylin A in liver fibrosis. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/41049034/
14. Nguyen HL, et al. (2025). A systematic review of evidence-based health benefits of Oroxylum indicum and its functional food potential. Foods. https://pubmed.ncbi.nlm.nih.gov/41154001/

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