IngredientsBaicalein (5,6,7-trihydroxyflavone) is a flavone, a type of flavonoid, originally isolated from the roots of Scutellaria baicalensis and Scutellaria lateriflora. It is chemically known by the PubChem CID 64982, and as a naturally occurring flavonoid it exhibits a chemical structure derived from the fundamental framework of 2-phenyl chromen-4-one (also known as 2-phenyl-1-benzopyran-4-one).
Baicalein belongs to flavones, a subclass of flavonoids, and its glycosidic conjugate baicalin, also known as baicalein-7-glucuronide, is a related compound. Baicalein is the aglycone of baicalin — that is, baicalin is baicalein with a glucuronic acid sugar moiety attached. Baicalein is metabolized and converted mainly to baicalin following intake in animals and humans.
Both baicalein and baicalin occur naturally in the roots of Scutellaria baicalensis Georgi, as well as in the leaves of Thymus vulgaris L. (thyme) and Oroxylum indicum (L.) Benth. These compounds are the main flavonoids in the roots of Scutellaria baicalensis Georgi, and phytochemical studies have also revealed them in other Scutellaria species such as S. lateriflora L.
Baicalein is widely distributed in plants of the genus Scutellaria (Lamiaceae) as a major constituent of fruit, root bark, and leaves, while baicalin is found in abundant quantities in leaves and stem bark. Chrysin, baicalin, scutellarein, baicalein, and wogonin are the main active components in S. baicalensis roots. The shoots of S. baicalensis also contain abundant flavonoids, including baicalin, baicalein, scutellarin, apigenin, chrysin, and several glucuronide forms.
Baicalein can be biosynthesized from phenylalanine, an initial precursor, via serial enzymatic reactions mediated by phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, cinnamate-CoA ligase, chalcone synthase, chalcone isomerase, flavone synthase II, and flavone 6-hydroxylase.
Baicalein is available as a dietary supplement and research compound in several forms, including standardized root extracts of S. baicalensis, isolated baicalein powder, and oral tablet formulations. Baicalein has two crystal forms, α-form and β-form. The crystalline pattern of naturally occurring baicalein is the α-form, which has very low bioavailability, a limitation widely described in the literature. As a result, pharmaceutical development has focused on modified formulations such as chewable tablets and, in clinical research, a specifically engineered tablet form. In at least one clinical Phase I study, the test drug specification was 500 mg per tablet, which contained 100 mg of baicalein per tablet.
Scutellaria baicalensis Georgi, or Chinese skullcap, has been widely used as a medicinal plant in China for thousands of years, where the preparation from its roots is called Huang-Qin. It has been applied in the treatment of diarrhea, dysentery, hypertension, hemorrhaging, insomnia, inflammation, and respiratory infections.
Chinese people have used the dried root of this medicinal plant for more than 2,000 years. It is known as Huang-Qin in the traditional Chinese medicine system and is now listed officially in the Chinese Pharmacopoeia.
It was first mentioned in the Shen Nong Ben Cao Jing (Divine Husbandman's Classic of the Materia Medica) from the Qin or Eastern Han dynasty (25–220 CE). Traditional uses of S. baicalensis date back to the Western Zhou Dynasty around 1,000 BC, where it was used to treat liver and lung diseases. The formulas in the Discussion of Cold-Induced Disorders (Shang Han Lun), by Zhang Zhong-Jing (Han Dynasty, 220 CE), included the formula Minor Bupleurum (Xiao Chai Hu Tang).
In Traditional Chinese Medicine, Scutellaria baicalensis (Huang Qin) is classified as a "heat-clearing" and "dampness-draining" herb. It primarily targets the Lung, Stomach, Gallbladder, and Large Intestine meridians, helping to purge toxins, reduce excess heat, and restore balance within the body.
Scutellaria baicalensis has long been a mainstay in Chinese medicine, and has been used for anxiety, depression, neurological conditions, and gastric distress. Scutellaria baicalensis is also the main component in the herbal remedy SST (Sho-saiko-to), used for liver problems such as hepatitis, hepatic fibrosis, and carcinoma.
Scutellaria baicalensis is a widely used traditional herbal medicine in China and Korea, known as 'Huang-Qin' and 'Hwang-Gum' respectively. The plant is widely found in China, Russia, Mongolia, and Japan. Scutellaria lateriflora, a related species, has been used in traditional Native American medicine for nervous tension and various psychiatric and neurological problems.
More than 40 compounds have been isolated from the root, including terpenoids, volatile oils, polysaccharides, beta-sitosterol, and flavonoids such as baicalin. Significant active constituents found in the plant's root include flavonoids and flavonoid glycosides, such as wogonin, baicalein, baicalin, oroxylin A, scutellarein, and norwogonin.
Baicalin is 5,6-dihydroxy-7-O-glucuronide flavone, and baicalein is its aglycone. These two compounds are closely biochemically linked. Baicalin is a flavone glycoside, and after its hydrolysis it converts into the aglycone baicalein. Because much of the existing pharmacological research concerns both compounds, it is important to note that many biological effects attributed to oral Scutellaria preparations involve a mixture of both, with conversion occurring in the gut and systemically.
Because baicalein blocks inflammatory mediators including LOX-1, COX-2, PGE2, and NF-κB, it may have anti-inflammatory and antioxidant effects. As with many bioflavonoids, baicalein inhibits phosphorylation of many fundamental signaling protein kinases; for example, it inhibits the ERK/MAPK signaling cascade, acting on the phosphorylation of MEK-1 by Raf-1 and inducing dampening of NF-κB.
The anti-inflammatory effect of baicalein depends on reducing the expression of inflammatory factors involved in the regulation of several signaling pathways, including MAPK, FoxO1, TLR4/NF-κB, STAT/NF-κB, and SOCS3. Baicalein inhibits NF-κB activation by activating PI3K/Akt and SIRT1 pathways and inhibiting the HMGB1/TLR4 signaling pathway, and alleviates inflammatory responses by inhibiting NLRP3 inflammasome activation.
The flavonoid has been shown to inhibit certain types of lipoxygenases. Lipoxygenase (LOX) inhibition — particularly of 12-LOX and 15-LOX — is considered one of the more well-established direct enzymatic targets of baicalein, contributing to its anti-inflammatory and antioxidant effects.
Baicalein at concentrations up to 100 μM significantly inhibited the production of nitric oxide, IL-1α, IL-6, G-CSF, GM-CSF, VEGF, MCP-1, IP-10, LIX, and RANTES, as well as calcium release in RAW 264.7 cells induced by poly I:C (50 µg/mL). This is in vitro evidence only.
Baicalein protects against oxidative stress-induced injuries by modulation of superoxide dismutase (SOD) and catalase activity. This ability to quench oxidative stress is conveyed through the suppression of reactive oxygen species (ROS) generation. Cytoprotective effects of baicalein against H₂O₂-induced oxidative stress may be mediated through the Nrf2/NQO-1/HO-1 signaling pathway.
Baicalein, along with its glucuronide baicalin, is a positive allosteric modulator of the benzodiazepine site and a non-benzodiazepine site of the GABAA receptor, but with an affinity over 250× lower than diazepam. It displays subtype selectivity for α2 and α3 subunit-containing GABAA receptors. This mechanism has been proposed as relevant to its anxiolytic and anticonvulsant effects observed in preclinical models.
Baicalein is a flavonoid with antioxidant properties; upon oxidation, it forms several products including quinones. Low micromolar concentrations of baicalein, and especially its oxidized forms, inhibit the formation of alpha-synuclein fibrils. In addition, existing fibrils of alpha-synuclein are disaggregated by baicalein. The product of the inhibition reaction is predominantly a soluble oligomer of alpha-synuclein, in which the protein molecules have been covalently modified by baicalein quinone to form a Schiff base with a lysine side chain in alpha-synuclein.
Baicalein is a potent inhibitor of α-synuclein oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-synuclein fibrillation in cell-free systems. Among compounds examined for inhibition and disaggregation of α-syn, baicalein exhibited significant inhibition and disaggregation at low concentrations (IC₅₀ < 4 μM). These findings are based on in vitro and cell culture studies.
Baicalein has potential for arresting cancer cell growth via the MAPK pathway and apoptosis through ROS, 12-lipoxygenase, and PI3K/Akt. It possesses anti-cancer properties including suppressing cell growth and differentiation, inhibiting metastasis, accelerating apoptosis, and elevating autophagy. Induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for its cytotoxic and antitumor activities. These mechanisms have been demonstrated predominantly in cell culture and animal studies.
Decreasing inflammation, reducing oxidative stress, regulating the metabolism of lipids, and decreasing fibrosis, apoptosis, and steatosis are the main hepatoprotective mechanisms attributed to baicalein and baicalin. In order to improve lipid metabolism and reduce hepatic de novo lipogenesis, baicalein inhibits the CaMKK/AMPK/ACC pathway. Baicalein also has the capacity to reduce liver fibrosis, oxidative stress, and systemic inflammation in fatty liver disease. To reverse fibrosis, baicalein inhibits the synthesis of collagen (type I and α-1) chain and transforming growth factor (TGF)-β1.
Baicalein up-regulates the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, LXRα, and PPARγ, promotes cholesterol efflux, and inhibits lipid accumulation. Administration of baicalein also reduces the expression and secretion of TNF-α, IL-1β, and IL-6. These effects were observed in macrophage-derived foam cell models relevant to atherosclerosis research.
Preclinical evidence (animal/cell models): Baicalein, a major bioactive flavone of Scutellaria baicalensis Georgi, has demonstrated neuroprotective properties in several animal models of Parkinson's disease (PD). A systematic review and meta-analysis was conducted to assess the available preclinical evidence, ultimately identifying 20 studies from 7 databases up to December 2019.
Meta-analyses showed baicalein can significantly improve neurobehavioral function in animal models with PD, including in spontaneous motor activity tests, the pole test, the rotarod test, apomorphine-induced rotation tests, grid tests, and tremor tests. The possible mechanisms of baicalein for PD are regulating neurotransmitters, adjusting enzyme activity, antioxidation, anti-inflammatory activity, inhibiting protein aggregation, restoring mitochondrial dysfunction, inhibiting apoptosis, and autophagy. The findings preliminarily demonstrated that baicalein exerts potential neuroprotective effects through multiple signaling pathways in animal models of PD.
Baicalein attenuates Parkinson's disease in animal models by activating the BDNF/TrkB/CREB pathway, inhibiting the NLRP3/Caspase-1/GSDMD pathway, and induction of mitochondrial autophagy by activating the NIX/BNIP3 pathway and SIRT1/AMPK/mTOR pathway.
In in vitro experiments, baicalein (0.5, 5 μg/mL) could significantly ameliorate 6-OHDA-induced SH-SY5Y cell apoptosis from 31.56% in the 6-OHDA group to 18.90% and 21.61% respectively, and also promote neurite outgrowth of PC12 cells. In in vivo experiments, baicalein had no effect on apomorphine-induced rotations, but it could significantly attenuate muscle tremor of 6-OHDA-lesioned rats. Moreover, baicalein treatment could also increase tyrosine hydroxylase (TH)-positive neurons to 265.52% of the 6-OHDA group.
Evidence strength: Despite a vast number of preclinical studies on baicalin and baicalein, very few clinical trials have evaluated the efficacy and safety of these phytochemicals. The neuroprotective evidence for Parkinson's disease currently remains at the preclinical (animal and in vitro) stage. Baicalein could be a candidate for further clinical trials of PD.
Baicalein is a flavonoid compound found in the Chinese herb Scutellaria baicalensis, which has been shown to inhibit the formation and disaggregation of α-synuclein fibrils, and protect cells from aggregates of Aβ42 and α-synuclein. In cell culture, baicalein inhibits Aβ42 and α-syn oligomerization and protects SH-SY5Y and PC12 cells affected by Aβ42 and α-syn aggregates.
As a bioflavonoid, baicalein inhibits the ERK/MAPK signaling cascade; its anti-phosphorylation property includes preventing the phosphorylation of tau protein in APP/PS1 mice. Baicalein can prevent damage from Aβ binding to synapse-related sites that mediates reduction of synaptic loss and modulates the damage of glutamatergic synaptic transmission.
Evidence strength: Evidence for Alzheimer's disease is entirely preclinical (in vitro and animal models). No human clinical trials specifically targeting Alzheimer's disease with isolated baicalein have been identified in the reviewed literature.
The anti-inflammatory potential of baicalin and baicalein has been confirmed, and both molecules can be potent agents for the treatment of rheumatoid arthritis, respiratory diseases, inflammatory bowel diseases, cardiovascular diseases, hepatitis, kidney diseases, and neurodegenerative diseases.
The anti-arthritic effect of baicalein has been demonstrated in C57BL/6J mice subjected to collagen-induced arthritis (CIA), wherein baicalein regulated cytokine levels and ameliorated inflammation and arthritis. The arthritic score and number of affected joints significantly decreased in the baicalein group in comparison to the vehicle group, suggesting a decrease in inflammation.
Evidence strength: Anti-inflammatory activity is well-supported at the mechanistic, in vitro, and animal model level. According to the reviewed literature, these compounds have been mainly effective in the treatment of neurological and neurodegenerative diseases, hepatic and cardiovascular disorders, metabolic syndrome, and cancers through anti-inflammatory and antioxidant pathways. Robust human clinical trial data for isolated baicalein in inflammatory conditions remains limited.
Studies on baicalein have indicated that it possesses multiple beneficial characteristics, such as being effective against oxidative stress, acute and chronic inflammation, malignancy, and diabetes mellitus. Additionally, it has anti-thrombotic and anti-viral effects with cardioprotective, neuroprotective, eye-protective, and hepatoprotective features.
Baicalein has been investigated against numerous cancer types in preclinical settings, including prostate, lung, hepatocellular carcinoma, pancreatic, and colorectal cancers. The main mechanisms studied include: induction of apoptosis and autophagy, and inhibition of migration and metastasis are the main mechanisms for its cytotoxic and antitumor activities.
Despite its genotoxic effect in some models, baicalein did not induce mutations — a major problem of conventional anticancer drugs — suggesting that baicalein and related flavones are strong candidates for improved chemotherapeutic agents.
Evidence strength: All current anticancer evidence for baicalein is based on in vitro cell studies and animal models. No human clinical trials confirming anticancer efficacy for isolated baicalein have been reported in the literature searched. There is a paucity of information concerning these substances' therapeutic applications and optimum dosages.
Baicalein, a flavonoid belonging to the flavones subgroup, has exhibited significant antiviral effects against in vitro replication of dengue virus (DENV-2) in Vero cells, functioning at different stages of virus replication. Phase I pharmacokinetic studies of baicalein tablets were specifically developed in the context of potential influenza treatment. Baicalein is a biologically important flavonoid that can effectively inhibit the influenza virus.
A Phase I, randomized, double-blind, placebo-controlled dose-escalation study evaluated the safety, tolerability, and pharmacokinetic profile of multiple-dose baicalein tablets in healthy Chinese subjects, with a basis for further Phase II clinical trials of baicalein tablets against influenza virus.
Evidence strength: Antiviral data is largely preclinical (in vitro and animal). The clinical safety and pharmacokinetic studies completed to support antiviral use have been Phase I only, establishing safety but not therapeutic efficacy in human patients.
Baicalein can regulate the metabolism of lipids including 2-oxocarboxylic acid, α-linolenic acid, and pantothenate, and the secretion of bile. Activating AMPK is one of the crucial mechanisms by which baicalein exerts its effects on non-alcoholic fatty liver disease (NAFLD). Baicalein could alleviate fat accumulation in the liver by suppressing SREBP1 cleavage and activating AMPK, thereby inhibiting SREBP1 transcriptional activity and hepatic fat synthesis in vitro and in vivo.
Modern research has shown that S. baicalensis may be beneficial for liver support, consistent with its traditional use. Baicalin has been shown to have antifibrotic effects in laboratory studies.
Evidence strength: Hepatoprotective evidence is primarily from in vitro and animal models. Clinical studies in humans using isolated baicalein for liver disease have not been identified in the reviewed sources.
Accumulating evidence indicates that baicalin has favorable therapeutic effects on cardiovascular diseases. Previous studies have revealed therapeutic effects on atherosclerosis, myocardial ischemia/reperfusion injury, hypertension, and heart failure through anti-inflammatory, antioxidant, and lipid metabolism mechanisms.
The mechanisms include anti-inflammatory and antioxidant effects; inhibition of endothelial cell apoptosis; modulation of innate immunity; inhibition of vascular smooth muscle cell (VSMC) proliferation, migration, and contraction; modulation of coagulation and fibrinolytic systems; inhibition of myocardial hypertrophy; inhibition of myocardial fibrosis; and anti-apoptotic effects on cardiomyocytes.
Evidence strength: Cardiovascular evidence for baicalein specifically is predominantly derived from preclinical (in vitro and animal) studies. Much of the clinical literature in this area concerns Scutellaria extracts or baicalin as a whole, rather than isolated baicalein. Well-controlled human trials with isolated baicalein for cardiovascular endpoints have not been reported in the reviewed sources.
Natural compounds baicalein and baicalin show favorable antidiabetic properties. In particular, the predicted favorable absorption profile of baicalein makes this natural flavonoid a promising candidate for further investigations into the possibility of developing a formulation for use in the prevention of hyperglycemia-related diseases.
Emerging evidence has indicated that baicalin and baicalein possess hepatoprotective, anti-oxidative, anti-dyslipidemic, anti-lipogenic, anti-obese, anti-inflammatory, and anti-diabetic effects, being effective for treating obesity, insulin resistance, non-alcoholic fatty liver disease, and dyslipidemia in preclinical models.
Evidence strength: Antidiabetic effects are documented in rodent models and in vitro assays. Human clinical data for baicalein specifically as an antidiabetic agent has not been established in the reviewed sources.
Studies show that baicalin and baicalein have antibacterial activities against different pathological bacteria such as avian pathogenic Escherichia coli, Staphylococcus aureus, Helicobacter pylori, and Chlamydia trachomatis.
Evidence strength: Antimicrobial evidence is in vitro and animal-model based. No human clinical trials confirming antimicrobial efficacy of isolated baicalein have been identified in the reviewed sources.
Baicalein is associated with benefits to human health owing to its antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, antimicrobial, anti-aging, cardioprotective, neuroprotective, respiratory-protective, gastroprotective, liver-protective, and kidney-protective effects.
Single oral doses of 100–2,800 mg of baicalein were safe and well tolerated by healthy subjects in a single ascending dose study. Clinical laboratory assessments showed no signs of toxicity in the liver or kidney.
In a multiple-ascending-dose Phase I trial, 36 healthy subjects were randomized to receive 200, 400, and 600 mg of baicalein tablet or placebo once daily on day 1 and day 10, and three times daily on days 4–9.
The medication safety evaluation of baicalein chewable tablets revealed that multiple oral doses of baicalein are safe and well tolerated, with no serious accumulation in the dose range of 200–800 mg.
According to single-dose pharmacokinetic (PK) studies of baicalein in the range from 200 to 800 mg, baicalein exhibited a nonlinear PK profile with less than dose-proportional increases in exposure. The exposure of baicalein started to reach a plateau at the dose level of 600 mg, possibly due to the saturation of baicalein absorption.
The highest urinary excretion of baicalein and its metabolites peaked at 2 hours, followed by 12 hours, with a double-peak trend. Oral baicalein tablets were rapidly absorbed, with peak plasma levels reached within 2 hours after multiple administration.
In preclinical cell studies, baicalein at 0.5 and 5 μg/mL was used in in vitro neuroprotection experiments. In macrophage anti-inflammatory assays, concentrations up to 100 μM were evaluated. These are in vitro dosages and do not directly translate to human oral dosages.
Single oral doses of 100–2,800 mg of baicalein were safe and well tolerated by healthy subjects. Clinical laboratory assessments showed no signs of toxicity in the liver or kidney. The favorable safety profile and PK properties warrant further clinical studies for baicalein.
Baicalein tablets administered multiple times within the studied dose range were safe and well-tolerated in healthy Chinese subjects, with no serious or severe adverse effects.
Previous clinical trials have shown that baicalein chewable tablets are safe, and no signs of renal and hepatic toxicity were observed for single oral doses in the range of 100–2,800 mg and multiple oral doses in the range of 200–800 mg.
Baicalein has two crystal forms, α-form and β-form. The crystalline pattern of naturally occurring baicalein is the α-form, with very low bioavailability, limiting the therapeutic applications of naturally occurring baicalein. This low bioavailability is a recognized challenge in the translation of preclinical dose-response findings to human supplementation.
Drug interactions via CYP450 enzymes have been studied using various in vitro and in vivo methods. Inhibition of CYP450 enzymes may reduce a drug's metabolism, which often leads to increased drug effects or even toxicities, while induction of CYP450 enzymes may result in reduced drug effects via increased drug metabolism. Multiple studies have examined the effects of S. baicalensis and its bioactives on CYP enzymes in vitro or in vivo, with significant variations in findings, which may be related to experimental conditions, species differences, and concentrations/doses used.
One study found evidence that consumption of baicalin might lower blood levels of statin drugs, specifically examining the effect of the herbal medicine baicalin on pharmacokinetics of rosuvastatin, a substrate of organic anion-transporting polypeptide 1B1 (OATP1B1).
Baicalein influences drug metabolism and uptake inside the human body. This has been noted as a potential adverse consideration when baicalein is co-administered with other pharmaceutical drugs, particularly those relying on the same hepatic transport and metabolizing enzyme systems.
Published sources note that baicalein is an antagonist of the estrogen receptor, which may be relevant in the context of hormone-sensitive conditions. This property has been identified in in vitro research and noted as a consideration in the pharmacology literature, though human clinical implications require further study.
Scutellaria is contraindicated in cases of Cold from Spleen and Stomach deficiency in TCM classification. Being very cold and bitter, it can injure the Yang and the Spleen and Stomach Qi if taken for too long or in too big a dose.
Although in vitro and in vivo tests have shown the safe dose range and action time of baicalin, more in-depth studies on its toxicity in different animal models should be conducted before its application in the treatment of human clinical diseases. More clinical and mechanistic approaches are recommended to confirm the safety and efficacy of baicalein.
Health conditions that Baicalein may help support.
Baicalein, the aglycone flavonoid from Scutellaria baicalensis, inhibits NF-κB and STAT6 signaling pathways and reduces eosinophilic airway inflammation in asthma models. As the active metabolite of baicalin with superior bioavailability, it contributes to the anti-asthmatic activity documented for Baikal skullcap in preclinical studies.
Baicalein is the aglycone form of baicalin from Scutellaria baicalensis with potent anti-inflammatory and anti-allergic effects in the airway. It inhibits 5-lipoxygenase and 12-lipoxygenase, reducing leukotriene synthesis relevant to asthma and COPD, and is documented in TCM respiratory formulas.
Baicalein is a bioactive flavonoid from Scutellaria baicalensis (Baikal Skullcap) with documented in vitro activity against all morphological forms of B. burgdorferi and B. garinii, including spirochete, rounded, and biofilm forms. It was confirmed as the most effective phytochemical against biofilm-forming Borrelia in a 2015 PMC study. Additional neuroprotective effects are relevant to neurological Lyme manifestations.
Baicalein, an active flavone from Scutellaria baicalensis (Baikal skullcap), inhibited production of IL-6, IL-8, and MCP-1 in IL-1β- and TNF-α-activated human mast cells (HMC-1 line) dose-dependently via NF-κB pathway suppression, as published in PMC2206049 (Clinical and Molecular Allergy, 2007). It also inhibits 5-lipoxygenase, reducing leukotriene synthesis from mast cells.
Baicalein, a bioactive flavone from Scutellaria baicalensis (Baikal skullcap), has demonstrated consistent neuroprotective effects in animal models of Parkinson's disease. A 2020 systematic review and meta-analysis of 20 preclinical studies confirmed significant improvements in motor and dopaminergic outcomes. Clinical translation is underway but human trial data remain limited.
Baicalein is the aglycone of baicalin from Scutellaria baicalensis, with potent anti-inflammatory effects including inhibition of NF-κB, TNF-α, IL-1β, and LOX pathways. Preclinical studies in collagen-induced arthritis models show reduced synovial inflammation and bone erosion, making it relevant as a complementary approach to RA management.
Baicalein is a flavone from Baikal skullcap (Scutellaria baicalensis) with documented antiviral activity against influenza, SARS-CoV-2, HBV, HCV, HSV, HIV, and dengue. It inhibits viral RNA polymerase, neuraminidase, and entry into host cells. TCM has used Baikal skullcap for respiratory viral infections for 2,000+ years.
Body systems that Baicalein may help support.
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