Baicalein

Baicalein at a Glance

Baicalein is a flavone from Chinese skullcap (Scutellaria baicalensis) and the aglycone of baicalin, the glycoside that dominates the root.

Two mechanisms define its research: it is a 12/15-lipoxygenase inhibitor, and a GABA-A benzodiazepine-site modulator — the second underlying skullcap’s traditional sedative and anxiolytic use, and putting it in the same mechanistic family as apigenin.

It has early Phase I human safety data, which is more than most flavones manage, but no efficacy trial.

What It's Used For

Baicalein is a flavone and one of the principal actives of Chinese skullcap (Scutellaria baicalensis), where it occurs alongside — and in a metabolic couple with — its 7-O-glucuronide baicalin. This relationship is the key to reading its literature: baicalin is the abundant plant form and behaves as a colonic prodrug that gut bacteria hydrolyze back to baicalein, while orally-dosed baicalein is rapidly glucuronidated to baicalin ^{19Reference 19Zhang L et al. · 2011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →}.

The two interconvert, so many “baicalein” claims actually rest on baicalin studies, and the two are kept separate here. Baicalein’s own best-characterized actions are as a relatively selective 12/15-lipoxygenase inhibitor ^{3Reference 3van Leyen K et al. · 2006Baicalein and 12/15-lipoxygenase in the ischemic brainView study →} and a GABA-A benzodiazepine-site modulator ^{7Reference 7Wang H et al. · 2002Structure-activity relationship of Scutellaria flavonoids binding the benzodiazepine site of the GABA-A receptorView study →}, the mechanistic backbone of skullcap’s traditional calming use. Human work so far is limited to two Phase I safety/pharmacokinetic studies ^{1,2Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →}; every efficacy finding below is preclinical.

Two well-defined mechanisms:selective 12/15-lipoxygenase inhibition (anti-inflammatory, anti-ferroptotic) ^{3,5Reference 3van Leyen K et al. · 2006Baicalein and 12/15-lipoxygenase in the ischemic brainView study →Reference 5Guo S et al. · 2024Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosisView study →} and binding at the GABA-A benzodiazepine site (anxiolytic-like in rodents) ^{7,9Reference 7Wang H et al. · 2002Structure-activity relationship of Scutellaria flavonoids binding the benzodiazepine site of the GABA-A receptorView study →Reference 9Liao JF et al. · 2003AnimalAnxiolytic-like effects of baicalein and baicalin in the Vogel conflict test in miceView study →}.

Human data are safety-only:oral baicalein tablets were well tolerated across Phase I single- and multiple-dose studies — but there are no efficacy trials for any indication ^{1,2Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →}.

The honest headline:the neuroprotective, antiviral, anticancer and anti-gout signals are all animal or in-vitro, and the aglycone is poorly absorbed without a solubility-enhancing formulation ^{19,20Reference 19Zhang L et al. · 2011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →Reference 20Liu J et al. · 2006A baicalein–hydroxypropyl-β-cyclodextrin inclusion complex: preparation and in-vivo evaluationView 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. Baicalein’s efficacy evidence is preclinical, so scores stay low by design. Each application links to its write-up.

Mechanisms

Target / pathway	Effect	Relevant to
12/15-lipoxygenase (ALOX15/ALOX12) inhibition	↓ lipid peroxidation, ↓ ferroptosis, ↓ neuro/renal injury	anti-inflammatoryneuroprotection
GABA-A benzodiazepine site (positive modulation)	↑ GABAergic tone	anxiolytic; sedative-additive interaction
Nrf2 activation (antioxidant response)	↑ endogenous antioxidant defense	cytoprotection
NF-κB / COX-2 suppression	↓ TNF-α, IL-6, prostaglandins	anti-inflammatory
Xanthine-oxidase inhibition	↓ uric-acid production	hyperuricemia (preclinical)
Influenza neuraminidase; SARS-CoV-2 3CLpro / RdRp	↓ viral replication (in vitro)	antiviral
UGT (glucuronidation) substrate; OATP1B1 (as baicalin)	altered drug conjugation/transport	drug-interaction risk

Pharmacokinetics

Pharmacokinetics are load-bearing. Baicalein is a lipophilic trihydroxyflavone with poor aqueous solubility, and it undergoes extensive first-pass phase-II conjugation — rapidly glucuronidated (and sulfated) in gut wall and liver, its principal metabolite being baicalin, in a process governed by the coupling of UGT enzymes and efflux transporters ^{19Reference 19Zhang L et al. · 2011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →}. Net systemic exposure of the free aglycone after oral dosing is therefore low, and solubility-enhancing formulations (e.g. cyclodextrin complexation) markedly improve absorption ^{20Reference 20Liu J et al. · 2006A baicalein–hydroxypropyl-β-cyclodextrin inclusion complex: preparation and in-vivo evaluationView study →}. The baicalein↔baicalin interconversion — aglycone glucuronidated on absorption, glycoside deglucuronidated back by gut microbiota — means the two forms behave as a metabolic couple, which is the main reason isolate-vs-glycoside attribution is difficult. Human Phase I studies show measurable, dose-proportional absorption of oral baicalein tablets, with relatively rapid elimination of the aglycone and longer apparent exposure via the baicalin metabolite ^{1,2Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →}.

Clinical trials

Isolated-baicalein human data consist of two Phase I studies in healthy adults — a randomized, double-blind, placebo-controlled multiple-ascending-dose safety/PK study ^{1Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →} and a single-dose plus food-effect study ^{2Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →} — both showing good tolerability. There are no efficacy trials; the frequently-cited influenza Phase IIa trial could not be verified as a published RCT.

Completed	Planned	Terminated	Preclinical
2Phase I (safety/PK)	Efficacy — early	—	Extensive

Last checked: July 2026.

Toxicity & Safety

Baicalein is a dietary-type flavone from a long-used medicinal root and was well tolerated across its Phase I human dosing, so a low toxicity classification is defensible for ordinary exposures ^{1,2Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →}. The practical cautions are pharmacological. Its GABA-A benzodiazepine-site activity makes additive CNS depression with benzodiazepines, alcohol and other sedatives plausible ^{7,8Reference 7Wang H et al. · 2002Structure-activity relationship of Scutellaria flavonoids binding the benzodiazepine site of the GABA-A receptorView study →Reference 8Hui KM et al. · 2000Interaction of Scutellaria baicalensis flavones with the benzodiazepine site of the GABA-A receptorView study →}. Because it is a heavily glucuronidated UGT substrate, it can compete with the glucuronidation of co-administered drugs ^{19Reference 19Zhang L et al. · 2011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →}; the related interactions best documented in humans belong to the glycoside baicalin, which raised rosuvastatin exposure via OATP1B1 inhibition ^{21Reference 21Fan L et al. · 2008The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1View study →} and altered nifedipine pharmacokinetics via CYP3A inhibition in animals ^{22Reference 22Cheng ZY et al. · 2014AnimalBaicalin CYP3A inhibition and protein-binding displacement alter nifedipine pharmacokinetics in ratsView study →} — so statin and CYP3A-substrate interactions should be treated as plausible. A baicalein–warfarin interaction is sometimes mentioned but is theoretical only, with no direct study. There is no pediatric or organ-impairment data.

Dosage

There is no established therapeutic dose for baicalein. The Phase I studies administered oral baicalein tablets across an escalating range to characterize tolerability and pharmacokinetics — not to establish an efficacy dose ^{1,2Reference 1Li M et al. · 2021Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose studyView study →Reference 2Dong R et al. · 2021Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjectsView study →}. All efficacy data are preclinical, at animal mg/kg doses that do not translate directly, and plain baicalein powder is poorly absorbed without a solubility-enhancing formulation ^{19,20Reference 19Zhang L et al. · 2011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →Reference 20Liu J et al. · 2006A baicalein–hydroxypropyl-β-cyclodextrin inclusion complex: preparation and in-vivo evaluationView study →}. Nothing here is a recommendation.

References

Li M, et al. (2021). Safety, tolerability, and pharmacokinetics of oral baicalein tablets in healthy Chinese subjects: a multiple-ascending-dose study. Clinical and Translational Science. https://pubmed.ncbi.nlm.nih.gov/34156161/
Dong R, Li L, Gao H, et al. (2021). Safety and pharmacokinetics of baicalein tablets after single-dose administration and with food in healthy subjects. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/33753147/
van Leyen K, et al. (2006). Baicalein and 12/15-lipoxygenase in the ischemic brain. Stroke. https://pubmed.ncbi.nlm.nih.gov/17053180/
Tajbakhsh A, Hosseinpour-Soleimani F, Abedi M, et al. (2025). 12/15-lipoxygenase inhibition by baicalein in post-stroke neuroinflammation. Stroke. https://pubmed.ncbi.nlm.nih.gov/40052290/
Guo S, Zhou L, Liu X, et al. (2024). Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosis. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/38805781/
Lee W, Ku SK, Bae JS, et al. (2015). Anti-inflammatory effects of baicalin, baicalein and wogonin in vitro and in vivo. Inflammation. https://pubmed.ncbi.nlm.nih.gov/25249339/
Wang H, Hui KM, Chen Y, et al. (2002). Structure-activity relationship of Scutellaria flavonoids binding the benzodiazepine site of the GABA-A receptor. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/12494329/
Hui KM, et al. (2000). Interaction of Scutellaria baicalensis flavones with the benzodiazepine site of the GABA-A receptor. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/10705749/
Liao JF, et al. (2003). Anxiolytic-like effects of baicalein and baicalin in the Vogel conflict test in mice. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/12620506/
Fong SYK, Li C, Ho YC, et al. (2017). Brain uptake of Scutellaria flavones and the anxiolytic effect in mice. Molecular Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/28426226/
Wang Y, Wei N, Li X (2020). Preclinical evidence and mechanisms of baicalein in Parkinson’s disease: a systematic review and meta-analysis. Frontiers in Aging Neuroscience. https://pubmed.ncbi.nlm.nih.gov/33101006/
Zhu Q, Zhuang X, Lu J (2019). Neuroprotective effects of baicalein in animal models of Parkinson’s disease: a systematic review. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/30385133/
Chmiel M, Stompor-Gorący M (2023). Baicalein in the prevention and treatment of human diseases: a mechanistic review. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/36902160/
Hour MJ, Huang SH, Chang CY, et al. (2013). Baicalein inhibits the neuraminidase of pandemic H1N1 and seasonal influenza A. Evidence-Based Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/23864896/
Liu H, Ye F, Sun Q, et al. (2021). Scutellaria baicalensis extract and baicalein inhibit SARS-CoV-2 and its 3CL protease in vitro. Journal of Enzyme Inhibition and Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/33491508/
Zandi K, Musall K, Oo A, et al. (2021). Baicalin and baicalein inhibit SARS-CoV-2 RNA-dependent RNA polymerase. Microorganisms. https://pubmed.ncbi.nlm.nih.gov/33921971/
Chen Y, Zhao Z, Li Y, et al. (2021). Baicalein alleviates hyperuricemia by promoting uric-acid excretion and inhibiting xanthine oxidase. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/33075645/
Wan Y, Shen K, Yu H, et al. (2023). Baicalein limits osteoarthritis development by inhibiting chondrocyte ferroptosis. Free Radical Biology and Medicine. https://pubmed.ncbi.nlm.nih.gov/36657732/
Zhang L, Li C, Lin G, et al. (2011). Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transporters. The AAPS Journal. https://pubmed.ncbi.nlm.nih.gov/21607811/
Liu J, Qiu L, Gao J, et al. (2006). A baicalein–hydroxypropyl-β-cyclodextrin inclusion complex: preparation and in-vivo evaluation. International Journal of Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/16459034/
Fan L, et al. (2008). The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1. Clinical Pharmacology & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/17851565/
Cheng ZY, Tian X, Gao J, et al. (2014). Baicalin CYP3A inhibition and protein-binding displacement alter nifedipine pharmacokinetics in rats. PLoS One. https://pubmed.ncbi.nlm.nih.gov/24498050/