Baicalein

Pharmacology & Research

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 hydrolyse back to baicalein, while orally-dosed baicalein is rapidly glucuronidated to baicalin ^{19Reference 192011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →}. The two interconvert, so many “baicalein” claims actually rest on baicalin studies — this page keeps them separate. Baicalein’s own best-characterised 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 7Liao JF 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 2Pang H 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.

1. Anti-inflammatory (12/15-LOX)

Baicalein is a canonical, relatively selective inhibitor of 12/15-lipoxygenase (ALOX15/ALOX12), and this drives most of its anti-inflammatory and anti-ferroptotic effects: it reduced lipoxygenase-driven injury in the ischemic brain ^{3Reference 3van Leyen K et al. · 2006Baicalein and 12/15-lipoxygenase in the ischemic brainView study →}, limited post-stroke neuroinflammation ^{4Reference 42025(2025). 12/15-lipoxygenase inhibition by baicalein in post-stroke neuroinflammation. Stroke. https://pubmed.ncbi.nlm.nih.gov/40052290/View study →}, and protected against cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosis ^{5Reference 52024Baicalein alleviates cisplatin-induced acute kidney injury by inhibiting ALOX12-dependent ferroptosisView study →}. A head-to-head study confirmed anti-inflammatory activity for the baicalein arm specifically ^{6Reference 6Dinda B et al. · 2015In vitroAnti-inflammatory effects of baicalin, baicalein and wogonin in vitro and in vivoView study →}, and the same anti-ferroptotic mechanism limited cartilage degradation in a rodent osteoarthritis model ^{18Reference 182023Baicalein limits osteoarthritis development by inhibiting chondrocyte ferroptosisView study →}.

Gap: all animal or cell-based, with no human anti-inflammatory endpoint, and the effect is partly shared with (and confounded by) baicalin ^{6Reference 6Dinda B et al. · 2015In vitroAnti-inflammatory effects of baicalin, baicalein and wogonin in vitro and in vivoView study →}.

2. Anxiolytic (GABA-A)

Baicalein binds the benzodiazepine site of the GABA-A receptor — structure-activity work ties the affinity to its 5,7-dihydroxyflavone core ^{7,8Reference 7Liao JF 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 →} — and produces anxiolytic-like effects in the Vogel conflict test, with brain uptake of the flavone tracking the behavioural effect ^{9,10Reference 9Liao JF et al. · 2003AnimalAnxiolytic-like effects of baicalein and baicalin in the Vogel conflict test in miceView study →Reference 102017AnimalBrain uptake of Scutellaria flavones and the anxiolytic effect in miceView study →}.

Gap: rodent-only, and both baicalein and baicalin are active in the Vogel test, so the aglycone’s contribution isn’t cleanly isolated; there is no human anxiety data ^{9Reference 9Liao JF et al. · 2003AnimalAnxiolytic-like effects of baicalein and baicalin in the Vogel conflict test in miceView study →}.

3. Neuroprotective

Two systematic reviews/meta-analyses of animal studies report consistent neuroprotection across rodent Parkinson’s and focal-ischemia models, via 12/15-LOX inhibition, antioxidant action and reduced protein aggregation ^{11,12,3Reference 112020Meta-analysisPreclinical evidence and mechanisms of baicalein in Parkinson’s disease: a systematic review and meta-analysisView study →Reference 122019Systematic reviewNeuroprotective effects of baicalein in animal models of Parkinson’s disease: a systematic reviewView study →Reference 3van Leyen K et al. · 2006Baicalein and 12/15-lipoxygenase in the ischemic brainView study →}.

Gap: these are meta-analyses of animal studies with acknowledged risk of bias; there is no clinical neurological data ^{11,12Reference 112020Meta-analysisPreclinical evidence and mechanisms of baicalein in Parkinson’s disease: a systematic review and meta-analysisView study →Reference 122019Systematic reviewNeuroprotective effects of baicalein in animal models of Parkinson’s disease: a systematic reviewView study →}.

4. Antiviral

In cell-free and cell-culture assays, baicalein inhibits the neuraminidase of pandemic and seasonal influenza A ^{14Reference 142013Baicalein inhibits the neuraminidase of pandemic H1N1 and seasonal influenza AView study →} and inhibits SARS-CoV-2 replication by targeting the 3CL protease ^{15Reference 152021In vitroScutellaria baicalensis extract and baicalein inhibit SARS-CoV-2 and its 3CL protease in vitroView study →} and RdRp ^{16Reference 162021Baicalin and baicalein inhibit SARS-CoV-2 RNA-dependent RNA polymeraseView study →}.

Gap: entirely in-vitro. A human influenza efficacy trial is often claimed in secondary sources but could not be verified — do not read these as clinical antiviral evidence ^{14,15,16Reference 142013Baicalein inhibits the neuraminidase of pandemic H1N1 and seasonal influenza AView study →Reference 152021In vitroScutellaria baicalensis extract and baicalein inhibit SARS-CoV-2 and its 3CL protease in vitroView study →Reference 162021Baicalin and baicalein inhibit SARS-CoV-2 RNA-dependent RNA polymeraseView study →}.

5. Hyperuricemia / gout

In hyperuricemic rodents, baicalein lowered uric acid by inhibiting xanthine oxidase and promoting urate excretion ^{17Reference 172021Baicalein alleviates hyperuricemia by promoting uric-acid excretion and inhibiting xanthine oxidaseView study →}.

Gap: preclinical; the broader metabolic/insulin-sensitising claims in this space rest on baicalin, not the aglycone ^{17Reference 172021Baicalein alleviates hyperuricemia by promoting uric-acid excretion and inhibiting xanthine oxidaseView study →}.

6. Anticancer

Across many cancer cell lines and some xenografts, baicalein is pro-apoptotic and anti-proliferative (caspase activation, cell-cycle arrest, ferroptosis), as summarised in a mechanistic review ^{13Reference 132023ReviewBaicalein in the prevention and treatment of human diseases: a mechanistic reviewView study →}.

Gap: entirely preclinical, at concentrations often above achievable human exposure; there is no human oncology data, and some cited targets (e.g. CDK1) appear only in whole-decoction network-pharmacology work, not clean baicalein studies ^{13Reference 132023ReviewBaicalein in the prevention and treatment of human diseases: a mechanistic reviewView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
12/15-lipoxygenase (ALOX15/ALOX12) inhibition	↓ lipid peroxidation, ↓ ferroptosis, ↓ neuro/renal injury	anti-inflammatory, neuroprotection
GABA-A benzodiazepine site (positive modulation)	↑ GABAergic tone	anxiolytic; sedative-additive interaction
Nrf2 activation (antioxidant response)	↑ endogenous antioxidant defence	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 192011Hepatic 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 202006A 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 2Pang H 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 randomised, 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 2Pang H 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.

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 2Pang H 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 7Liao JF 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 192011Hepatic 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. · 2008Baicalin increases the plasma exposure of rosuvastatin via OATP1B1 inhibition in humansView study →} and altered nifedipine pharmacokinetics via CYP3A inhibition in animals ^{22Reference 222014AnimalBaicalin 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 paediatric 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 characterise 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 2Pang H 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 192011Hepatic and intestinal disposition of baicalein: coupling of conjugation enzymes and transportersView study →Reference 202006A baicalein–hydroxypropyl-β-cyclodextrin inclusion complex: preparation and in-vivo evaluationView study →}. Nothing here is a recommendation.

References