Baicalein is a flavonoid from Scutellaria baicalensis (Chinese skullcap) with a tri-hydroxyl structure that directly scavenges free radicals while activating Nrf2 antioxidant pathways and inhibiting NF-κB inflammatory signaling, with promising preclinical evidence for neuroprotection, cardiovascular benefits, and anti-cancer properties, though human clinical research remains limited, typically supplemented at 100-600mg daily of purified compound or 500-2,000mg of standardized Scutellaria extract (5-20% baicalein), with enhanced efficacy through liposomal or nanoparticle formulations that overcome its poor water solubility and extensive glucuronidation.
Alternative Names: 5,6,7-Trihydroxyflavone, 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one, Baicalein flavone, Huang Qin flavonoid, Scutellaria flavonoid
Categories: Flavonoid, Flavone, Phytochemical, Antioxidant, Traditional Chinese Medicine component
Primary Longevity Benefits
- Neuroprotection
- Anti-inflammatory effects
- Antioxidant activity
- Cardiovascular protection
Secondary Benefits
- Anti-cancer properties
- Hepatoprotection
- Anti-viral activity
- Anti-bacterial effects
- Blood glucose regulation
- Anxiolytic effects
- Anti-allergic properties
- Gut health support
Mechanism of Action
Baicalein exerts its diverse biological effects through multiple molecular mechanisms and signaling pathways. As a potent antioxidant, baicalein directly scavenges reactive oxygen species (ROS) including superoxide anions, hydroxyl radicals, and peroxynitrite due to its tri-hydroxyl structure at positions 5, 6, and 7 in the A-ring. This structure allows for efficient electron donation and stabilization of resulting radicals through resonance. Beyond direct scavenging, baicalein activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by modifying Keap1 cysteine residues, leading to nuclear translocation of Nrf2 and subsequent upregulation of antioxidant enzymes including heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase (GST), and γ-glutamylcysteine synthetase (γ-GCS).
Baicalein exhibits potent anti-inflammatory properties primarily through inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway. It blocks IκB kinase (IKK) activation, preventing IκB phosphorylation and subsequent NF-κB nuclear translocation, thereby reducing the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Additionally, baicalein inhibits the NLRP3 inflammasome assembly and activation, reducing IL-1β and IL-18 production. It also suppresses cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, decreasing prostaglandin E2 (PGE2) and nitric oxide (NO) production.
In the central nervous system, baicalein provides neuroprotection through multiple mechanisms. It modulates glutamate receptors, particularly NMDA receptors, reducing excitotoxicity. Baicalein inhibits 12/15-lipoxygenase (12/15-LOX), an enzyme implicated in neuronal death following stroke and neurodegenerative diseases. It also promotes neurogenesis by enhancing brain-derived neurotrophic factor (BDNF) expression and activating the tropomyosin receptor kinase B (TrkB) signaling pathway.
Baicalein crosses the blood-brain barrier, though in limited amounts, and reduces neuroinflammation by inhibiting microglial activation. For cardiovascular protection, baicalein inhibits platelet aggregation by antagonizing thromboxane A2 receptors and inhibiting phospholipase C activation. It improves endothelial function by enhancing nitric oxide (NO) production through increased endothelial nitric oxide synthase (eNOS) activity and reduced NO degradation. Baicalein also inhibits vascular smooth muscle cell proliferation and migration by blocking mitogen-activated protein kinase (MAPK) signaling pathways.
In cancer cells, baicalein induces apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways. It activates caspase cascades, increases the Bax/Bcl-2 ratio, and induces cytochrome c release from mitochondria. Baicalein inhibits multiple oncogenic signaling pathways including PI3K/Akt/mTOR, MAPK/ERK, and Wnt/β-catenin. It also suppresses cancer cell invasion and metastasis by inhibiting matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT).
For metabolic regulation, baicalein improves insulin sensitivity by activating the AMP-activated protein kinase (AMPK) pathway and enhancing glucose transporter type 4 (GLUT4) translocation to the cell membrane. It inhibits α-glucosidase and α-amylase, reducing carbohydrate digestion and postprandial glucose spikes. Baicalein also modulates adipocyte differentiation and function through peroxisome proliferator-activated receptor gamma (PPARγ) regulation. Baicalein’s antiviral properties involve direct binding to viral proteins, inhibition of viral enzymes (particularly viral proteases and polymerases), and interference with viral attachment and entry into host cells.
It also enhances host antiviral immune responses by modulating interferon (IFN) signaling pathways. The molecular structure of baicalein, with its planar flavone backbone and hydroxyl groups, allows it to interact with various cellular receptors, enzymes, and signaling molecules, contributing to its pleiotropic effects. However, its limited water solubility and extensive phase II metabolism (primarily glucuronidation) affect its bioavailability and in vivo efficacy.
Optimal Dosage
Disclaimer: The following dosage information is for educational purposes only. Always consult with a healthcare provider before starting any supplement regimen, especially if you have pre-existing health conditions, are pregnant or nursing, or are taking medications.
The optimal dosage of baicalein is not well-established due to limited clinical trials
specifically using purified baicalein. Based on the available human studies and traditional use of Scutellaria baicalensis, dosages typically range from 100-600 mg of purified baicalein daily. Clinical safety studies have tested single doses up to 2800 mg without significant adverse effects, though such high doses are not typically recommended for regular use.
When using Scutellaria baicalensis (Huang Qin) extracts standardized for baicalein content (typically 5-20%), recommended dosages range from 500-2000 mg of the extract daily, providing approximately 25-400 mg of baicalein.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Neuroprotection | 200-400 mg of purified baicalein daily, or 1000-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Limited human data available. Dosages extrapolated from animal studies and preliminary human research. May require consistent use for several months to observe benefits. Blood-brain barrier penetration is limited, which may affect efficacy. |
| Anti-inflammatory effects | 200-600 mg of purified baicalein daily, or 1000-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Effects may be dose-dependent, with higher doses generally providing stronger anti-inflammatory activity. May take 2-4 weeks to observe significant benefits. Often used in combination with other anti-inflammatory compounds for synergistic effects. |
| Antioxidant support | 100-300 mg of purified baicalein daily, or 500-1500 mg of standardized Scutellaria extract (10-20% baicalein) | Lower doses may be sufficient for general antioxidant support. Higher doses may be warranted during periods of increased oxidative stress. Benefits from consistent daily use rather than occasional supplementation. |
| Cardiovascular protection | 200-400 mg of purified baicalein daily, or 1000-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Dosages based primarily on animal studies and limited human research. May be most effective when used consistently for at least 8-12 weeks. Often used in combination with other cardioprotective herbs or nutrients. |
| Liver protection | 200-600 mg of purified baicalein daily, or 1000-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Higher doses may be used for acute liver support, while lower doses are appropriate for long-term maintenance. Should be used under medical supervision in individuals with liver disease. |
| Anti-viral support | 300-600 mg of purified baicalein daily, or 1500-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Higher doses typically used during active viral infections, with lower doses for preventive purposes. Duration of use depends on the specific viral condition being addressed. Often combined with other immune-supporting compounds. |
| Blood glucose regulation | 200-400 mg of purified baicalein daily, or 1000-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Should be used under medical supervision in individuals with diabetes or those taking glucose-lowering medications. May require monitoring of blood glucose levels to prevent hypoglycemia. |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Children (under 18 years) | Not recommended | Safety and efficacy have not been established in pediatric populations. Use only under direct medical supervision if deemed necessary. |
| Adults (18-65 years) | 100-600 mg of purified baicalein daily, or 500-2000 mg of standardized Scutellaria extract (10-20% baicalein) | Dosage should be adjusted based on individual response, body weight, and specific health condition. Start with lower doses and gradually increase as tolerated. |
| Seniors (over 65 years) | 100-400 mg of purified baicalein daily, or 500-1500 mg of standardized Scutellaria extract (10-20% baicalein) | Lower starting doses recommended due to potential changes in metabolism and elimination. May be more susceptible to drug interactions. Careful monitoring advised, especially in those with multiple medications or chronic conditions. |
| Pregnant or breastfeeding women | Not recommended | Insufficient safety data available. Avoid use unless specifically recommended by a healthcare provider familiar with herbal medicine in pregnancy and lactation. |
Bioavailability
Absorption Rate
Baicalein exhibits relatively poor oral bioavailability, typically ranging from 13-23% in animal studies, with human data suggesting similar limitations. This low bioavailability is attributed to several factors, including limited water solubility (approximately 0.052 mg/mL), extensive first-pass metabolism in the intestine and liver, and active efflux by P-glycoprotein and breast cancer resistance protein (BCRP) transporters in the intestinal epithelium. Upon oral administration, baicalein undergoes extensive phase II metabolism, primarily glucuronidation by UDP-glucuronosyltransferases (UGTs) in the intestinal epithelium and liver, forming baicalin (baicalein-7-O-glucuronide) and other glucuronide conjugates. This pre-systemic metabolism significantly reduces the amount of free baicalein reaching the systemic circulation.
Pharmacokinetic studies in humans show that baicalein reaches peak plasma concentrations (Cmax) within 0.5-3 hours after oral administration, with a relatively short plasma half-life of 4-6 hours for the parent compound. Interestingly, the glucuronide metabolites, particularly baicalin, often achieve higher plasma concentrations and longer half-lives (8-14 hours) than the parent compound. These metabolites may contribute to the biological effects of baicalein, as they can be deconjugated back to baicalein in target tissues by β-glucuronidases, particularly at sites of inflammation where these enzymes are often upregulated. Baicalein demonstrates moderate tissue distribution, with higher concentrations observed in the liver, kidneys, and lungs.
Limited penetration across the blood-brain barrier has been reported, with brain concentrations typically less than 5% of plasma concentrations, which may affect its efficacy for neurological conditions.
Enhancement Methods
Liposomal encapsulation: Incorporating baicalein into liposomes has been shown to increase bioavailability by 2-3 fold in animal studies by enhancing solubility, protecting from pre-systemic metabolism, and potentially bypassing efflux transporters, Nanoparticle formulations: Polymeric nanoparticles, solid lipid nanoparticles, and nanoemulsions can improve baicalein solubility and protect it from metabolism, potentially increasing bioavailability by 3-5 fold, Phospholipid complexes: Forming complexes with phospholipids (phytosomes) increases the lipophilicity of baicalein, enhancing its ability to cross cell membranes and improving bioavailability by 2-4 fold, Self-microemulsifying drug delivery systems (SMEDDS): These formulations can increase baicalein solubility and provide a large surface area for absorption, potentially improving bioavailability by 3-6 fold, Co-administration with P-glycoprotein and BCRP inhibitors: Natural compounds like quercetin or synthetic inhibitors may reduce efflux and enhance baicalein absorption, Cyclodextrin inclusion complexes: These can improve baicalein solubility and stability in the gastrointestinal environment, with β-cyclodextrin showing particular promise, Micronization: Reducing particle size increases the surface area available for dissolution and absorption, Co-administration with piperine: This black pepper alkaloid may inhibit glucuronidation enzymes and efflux transporters, potentially enhancing baicalein bioavailability, Structural modifications: Chemical derivatives of baicalein with improved physicochemical properties may offer enhanced bioavailability, though these are primarily in research stages, Enteric coating: Protects baicalein from degradation in the stomach and targets release in the intestines where absorption is more favorable
Timing Recommendations
Due to its relatively poor bioavailability and interaction with food components, the timing of baicalein administration can significantly impact its absorption and efficacy. Taking baicalein on an empty stomach (at least 30 minutes before meals or 2 hours after meals) may enhance absorption by minimizing interference from food components and digestive processes. However, some individuals may experience mild gastrointestinal discomfort when taking baicalein on an empty stomach, in which case taking it with a small amount of fat (such as a teaspoon of olive oil or coconut oil) may improve tolerability while potentially enhancing absorption through increased bile secretion and lymphatic transport. For neuroprotective and anti-inflammatory effects, consistent daily dosing is recommended, with some evidence suggesting that dividing the daily dose into two administrations (morning and evening) may provide more stable plasma levels.
When using baicalein for acute conditions such as viral infections, more frequent dosing (3-4 times daily) may be beneficial to maintain therapeutic levels, given its relatively short half-life. Co-administration with vitamin C may enhance the antioxidant effects of baicalein through synergistic mechanisms, though direct evidence for improved bioavailability is limited. Avoiding simultaneous intake with mineral supplements (particularly iron, calcium, and zinc) is advisable, as these may form complexes with baicalein and reduce absorption. For individuals taking medications, separating baicalein administration by at least 2 hours from medication intake may reduce the risk of potential interactions, particularly with drugs that are substrates for P-glycoprotein or BCRP transporters.
Safety Profile
Safety Rating
Side Effects
- Mild gastrointestinal discomfort (nausea, bloating, diarrhea)
- Headache (uncommon)
- Dizziness (rare)
- Dry mouth (uncommon)
- Skin rash or itching (rare, may indicate allergic reaction)
- Fatigue (uncommon)
- Mild sedation or drowsiness (particularly at higher doses)
- Potential mild hypoglycemic effects (more common with higher doses)
- Increased urination (due to mild diuretic effect)
Contraindications
- Known allergy or hypersensitivity to baicalein, Scutellaria species, or other plants in the Lamiaceae family
- Pregnancy and breastfeeding (due to insufficient safety data and potential hormonal effects)
- Scheduled surgery (discontinue at least 2 weeks before due to potential effects on blood clotting)
- Bleeding disorders (due to potential anticoagulant and antiplatelet effects)
- Hormone-sensitive conditions such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids (theoretical concern due to potential phytoestrogenic effects)
- Severe liver or kidney disease (due to limited data on metabolism and elimination in these conditions)
- Hypoglycemia or poorly controlled diabetes (due to potential glucose-lowering effects)
- Children under 18 years (due to insufficient safety data)
Drug Interactions
- Anticoagulant and antiplatelet medications (may have additive effects on blood clotting, increasing bleeding risk)
- Sedative medications and CNS depressants (may enhance sedative effects)
- Hypoglycemic medications (may enhance blood glucose-lowering effects, potentially causing hypoglycemia)
- Medications metabolized by cytochrome P450 enzymes, particularly CYP1A2, CYP2C9, CYP2C19, and CYP3A4 (baicalein may inhibit these enzymes, potentially increasing blood levels of affected drugs)
- Medications transported by P-glycoprotein or BCRP (baicalein may compete for the same transport mechanisms, affecting drug absorption and elimination)
- Hormone replacement therapy or hormonal contraceptives (theoretical interaction due to potential phytoestrogenic effects)
- Diuretic medications (may have additive effects on urine output)
- Medications with narrow therapeutic windows (warfarin, digoxin, lithium, etc.) should be used with caution due to potential interactions
Upper Limit
No established upper limit has been determined for baicalein in humans. Clinical studies have tested single doses up to 2800 mg and multiple doses up to 600 mg three times daily for 10 days without serious adverse effects. However, these studies were conducted in healthy volunteers under controlled conditions and for relatively short durations. Based on available research and the traditional use of Scutellaria baicalensis, a conservative upper limit for regular daily use would be approximately 800-1000 mg of purified baicalein for adults.
For Scutellaria extracts standardized to contain 10-20% baicalein, an upper limit of 3000-4000 mg of extract daily would be reasonable. However, these are theoretical limits based on limited data, and individual sensitivity may vary. As with any supplement, it is advisable to start with lower doses and gradually increase as tolerated, particularly for individuals with sensitive systems or pre-existing health conditions. Long-term safety studies (>3 months) are lacking, suggesting caution with extended use at high doses.
Regulatory Status
Fda Status
In the United States, purified baicalein is not approved as a drug by the FDA for any specific indication. It may be sold as a dietary supplement ingredient under the Dietary Supplement Health and Education Act (DSHEA) of 1994, provided it meets the definition of a dietary ingredient and was not first marketed as a drug. As a supplement ingredient, baicalein or Scutellaria extracts standardized for baicalein content cannot make claims to diagnose, treat, cure, or prevent any disease. Structure/function claims (e.g., ‘supports antioxidant defenses’) are permitted with appropriate disclaimer statements.
The FDA has not established a specific regulatory framework or monograph for baicalein. Scutellaria baicalensis root, the natural source of baicalein, is generally recognized as safe (GRAS) for use in dietary supplements and has a long history of use in traditional medicine. It is included in the FDA’s ‘Old Dietary Ingredient’ list, indicating it was marketed in the U.S. before October 15, 1994.
International Status
Eu: In the European Union, purified baicalein is not approved as a medicinal product by the European Medicines Agency (EMA). Scutellaria baicalensis root, which contains baicalein, may be used in traditional herbal medicinal products or food supplements, subject to national regulations in individual member states. The European Food Safety Authority (EFSA) has not approved any health claims for baicalein or Scutellaria extracts. As a novel food ingredient, highly concentrated baicalein extracts may require novel food authorization under Regulation (EU) 2015/2283 if they do not have a significant history of consumption in the EU before May 1997. In some EU countries, Scutellaria baicalensis is included in national pharmacopoeias and may be used in registered traditional herbal medicinal products.
Canada: Health Canada has not approved baicalein as a prescription drug. Scutellaria baicalensis is listed in the Natural Health Products Ingredients Database with traditional uses related to heat-clearing and detoxification according to Traditional Chinese Medicine principles. Products containing Scutellaria extracts standardized for baicalein content may be sold as Natural Health Products (NHPs) with appropriate licenses, though specific claims are limited and must be supported by evidence. Health Canada has not established specific monographs or regulatory frameworks specifically for purified baicalein.
Australia: The Therapeutic Goods Administration (TGA) has not approved baicalein as a prescription medicine in Australia. Scutellaria baicalensis is recognized in the TGA’s list of permitted ingredients for listed medicines. Products containing Scutellaria extracts standardized for baicalein content may be sold as listed complementary medicines, subject to quality and safety requirements. Specific therapeutic claims require higher levels of evidence and appropriate registration. The TGA recognizes the traditional use of Scutellaria baicalensis in Traditional Chinese Medicine.
China: In China, baicalein has the most advanced regulatory status. Scutellaria baicalensis (Huang Qin) is officially listed in the Chinese Pharmacopoeia, with baicalein serving as one of the quality control markers. Several pharmaceutical preparations containing Scutellaria extracts standardized for baicalein content are approved as traditional Chinese medicines for various indications, particularly for respiratory infections, liver disorders, and inflammatory conditions. Purified baicalein is used in some approved pharmaceutical preparations and is the subject of ongoing clinical research for specific indications, particularly for viral infections and inflammatory disorders.
Japan: In Japan, baicalein is not approved as a pharmaceutical drug. Scutellaria baicalensis root (Ogon in Japanese) is recognized in the Japanese Pharmacopoeia and is used in several Kampo (traditional Japanese herbal medicine) formulations, such as Sho-saiko-to and Saiko-keishi-to. Products containing Scutellaria extracts may be sold as Foods with Health Claims under appropriate categories if they meet the established requirements, though specific approved claims for baicalein have not been established.
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating |
|---|---|---|
| Baicalin | Baicalin is the 7-O-glucuronide metabolite of baicalein and naturally co-occurs in Scutellaria baicalensis. While baicalein has superior membrane permeability, baicalin has better water solubility and different pharmacokinetic properties. The combination provides complementary bioavailability profiles and potentially more sustained effects, as baicalin can be deconjugated back to baicalein by β-glucuronidases at target tissues, particularly at sites of inflammation. | 3 |
| Wogonin | Wogonin is another flavone found in Scutellaria baicalensis that works synergistically with baicalein. While both compounds share anti-inflammatory and antioxidant properties, they act through partially different mechanisms and target different signaling pathways. The combination provides more comprehensive modulation of inflammatory and oxidative processes than either compound alone, particularly for neuroinflammation and cancer prevention. | 3 |
| Quercetin | Quercetin enhances the bioavailability of baicalein by inhibiting P-glycoprotein and BCRP efflux transporters in the intestine. Additionally, quercetin and baicalein provide complementary antioxidant protection by scavenging different types of reactive oxygen species and activating antioxidant enzymes through different mechanisms. The combination offers more comprehensive protection against oxidative stress and inflammation. | 2 |
| Curcumin | Curcumin complements the anti-inflammatory effects of baicalein through different molecular targets. While baicalein primarily inhibits NF-κB and NLRP3 inflammasome, curcumin additionally targets COX-2, STAT3, and AP-1 pathways. The combination provides more comprehensive anti-inflammatory effects and has shown synergistic benefits in models of inflammatory diseases and cancer. Both compounds also face similar bioavailability challenges, and formulations addressing these limitations can benefit both. | 2 |
| Vitamin C (Ascorbic acid) | Vitamin C works synergistically with baicalein to enhance antioxidant protection. While baicalein primarily scavenges superoxide and hydroxyl radicals, vitamin C more effectively neutralizes peroxyl radicals and can regenerate oxidized baicalein back to its active form. The combination provides more comprehensive antioxidant coverage and potentially enhances the neuroprotective and anti-inflammatory effects of baicalein. | 2 |
| Piperine | Piperine, the active component in black pepper, can significantly enhance the bioavailability of baicalein by inhibiting glucuronidation enzymes (UGTs) and efflux transporters (P-glycoprotein). This reduces the pre-systemic metabolism of baicalein and increases its absorption. Additionally, piperine has complementary anti-inflammatory properties that may enhance the therapeutic effects of baicalein. | 2 |
| Resveratrol | Resveratrol and baicalein target complementary pathways in cellular protection and longevity promotion. While baicalein primarily activates Nrf2 and inhibits NF-κB, resveratrol activates SIRT1 and AMPK pathways. The combination provides more comprehensive modulation of cellular stress responses, metabolic regulation, and anti-aging mechanisms. Both compounds also have complementary effects on mitochondrial function and biogenesis. | 2 |
| Omega-3 fatty acids | Omega-3 fatty acids complement the anti-inflammatory effects of baicalein through different mechanisms. While baicalein primarily inhibits pro-inflammatory signaling pathways, omega-3s are incorporated into cell membranes and serve as precursors for anti-inflammatory and pro-resolving mediators like resolvins and protectins. The combination provides more comprehensive management of inflammatory processes and may be particularly beneficial for chronic inflammatory conditions. | 2 |
| Berberine | Berberine complements the metabolic and cardiovascular effects of baicalein. While baicalein primarily acts through antioxidant and anti-inflammatory mechanisms, berberine activates AMPK and improves insulin sensitivity through different pathways. The combination may provide more comprehensive benefits for metabolic syndrome, diabetes, and cardiovascular protection. Both compounds also have complementary effects on gut microbiota and intestinal health. | 2 |
| Phospholipids (as in phosphatidylcholine) | Phospholipids can form complexes with baicalein (phytosomes), significantly enhancing its bioavailability by increasing lipophilicity and membrane permeability. This is not merely an enhancement method but a synergistic interaction, as the phospholipid complex exhibits different pharmacokinetic properties and potentially enhanced therapeutic effects. Phospholipids also provide complementary benefits for cell membrane integrity and liver health. | 3 |
Antagonistic Compounds
| Compound | Interaction Type | Evidence Rating |
|---|---|---|
| Iron supplements | Iron can form complexes with the hydroxyl groups of baicalein, reducing its absorption and bioavailability. This physical-chemical interaction may occur when iron supplements are taken simultaneously with baicalein. Additionally, iron can catalyze the oxidation of baicalein, potentially reducing its antioxidant efficacy. | 2 |
| Calcium supplements | Calcium ions may form complexes with baicalein, potentially reducing its absorption and bioavailability when taken simultaneously. This interaction is primarily theoretical based on the chemical structure of baicalein and known interactions of similar flavonoids with divalent cations. | 1 |
| Prooxidants (e.g., certain forms of iron, copper) | Prooxidant compounds can accelerate the oxidation of baicalein, potentially reducing its stability and antioxidant efficacy. This chemical antagonism may be particularly relevant in supplement formulations containing multiple ingredients or when taken simultaneously. | 2 |
| UGT inducers (e.g., rifampin, phenobarbital, carbamazepine) | Compounds that induce UDP-glucuronosyltransferases (UGTs) may increase the glucuronidation of baicalein, potentially reducing its bioavailability and efficacy. This pharmacokinetic interaction could significantly affect the amount of free baicalein reaching target tissues. | 2 |
| Antioxidant antagonists (e.g., certain chemotherapy drugs like doxorubicin that rely on oxidative mechanisms) | The strong antioxidant properties of baicalein may potentially interfere with the therapeutic mechanisms of certain chemotherapy drugs that rely on oxidative damage to kill cancer cells. This theoretical antagonism is based on opposing mechanisms but lacks specific clinical evidence for baicalein. | 1 |
| Tannin-containing herbs and supplements | Tannins can bind to baicalein in the gastrointestinal tract, potentially reducing its absorption. This physical-chemical interaction may occur with herbs high in tannins such as green tea, black tea, and many berries when taken simultaneously with baicalein. | 2 |
| Alkaline pH modifiers (e.g., antacids, proton pump inhibitors) | Baicalein stability and solubility are pH-dependent, with potential degradation in alkaline environments. Medications that significantly increase gastrointestinal pH may theoretically affect the stability and absorption of baicalein, though specific clinical evidence is limited. | 1 |
| P-glycoprotein substrates (e.g., digoxin, certain antibiotics, HIV protease inhibitors) | Baicalein may compete with these medications for P-glycoprotein transporters, potentially affecting their absorption, distribution, and elimination. The clinical significance of this interaction is unclear and would depend on specific dosages and timing. | 1 |
| High-fat meals | While small amounts of fat may enhance baicalein absorption, very high-fat meals may delay gastric emptying and create a complex gastrointestinal environment that could potentially reduce the rate and extent of baicalein absorption. The net effect may vary depending on the specific formulation of baicalein and meal composition. | 1 |
Cost Efficiency
Relative Cost
Purified baicalein (≥98% purity) is relatively expensive compared to many common dietary supplements, with a relative cost rating of high to very high. This high cost is primarily due to the complex extraction and purification processes required, the relatively low concentration in the raw material (typically 5-20% in Scutellaria baicalensis root), and the growing demand for pharmaceutical-grade material for research and development. Standardized Scutellaria extracts with specified baicalein content (typically 5-20%) have a medium to high relative cost, significantly lower than purified baicalein but higher than many common herbal supplements. Whole Scutellaria baicalensis root powder or basic extracts (not standardized for baicalein content) have a low to medium relative cost and represent the most economical way to obtain some baicalein, albeit in variable and typically lower amounts.
Novel delivery systems designed to enhance bioavailability, such as liposomal or nanoparticle formulations, typically command premium prices, though they may potentially deliver more bioavailable baicalein.
Cost Per Effective Dose
For purified baicalein (≥98% purity), the cost per effective daily dose (200-400 mg) typically ranges from $3-8, making
it relatively expensive for long-term use. For standardized Scutellaria extracts (5-20% baicalein), the cost per effective daily dose (providing approximately 100-400 mg of baicalein from 1000-2000 mg of extract) ranges from $1-3, representing a more accessible option though still relatively expensive compared to many supplements. For whole Scutellaria root powder or basic extracts, the cost per daily dose (typically 2-6 grams of root powder or 1-3 grams of basic extract) ranges from $0.30-1.00, though the baicalein content is variable and often lower than the theoretically effective dose based on research studies. Enhanced delivery systems such as liposomal formulations typically cost $4-10 per daily dose, though
they may potentially deliver more bioavailable baicalein, potentially improving the cost-to-benefit ratio
despite the higher price point.
Value Analysis
The value proposition of baicalein varies significantly depending on the form, intended use, and individual health considerations. Purified baicalein, despite its high cost, may offer value for specific research applications or short-term therapeutic interventions where precise dosing is critical. However, for most consumers seeking general health benefits, the cost-to-benefit ratio does not currently justify the expense of purified baicalein supplements, particularly given the limited human clinical evidence and bioavailability challenges. Standardized Scutellaria extracts with verified baicalein content offer a more reasonable value proposition, providing a balance between cost and potential efficacy.
These products benefit from the potential synergistic effects of other compounds naturally present in Scutellaria, particularly baicalin and wogonin, which may enhance overall efficacy beyond what would be expected from baicalein alone. Whole Scutellaria root or basic extracts provide the best value for general health maintenance and traditional uses, supported by centuries of traditional use and a growing body of scientific evidence for the whole herb. While the baicalein content is lower and less standardized, the presence of multiple bioactive compounds may provide complementary benefits. For specific health conditions with stronger research support, such as inflammatory disorders or neuroprotection, the value proposition of standardized extracts improves, as the potential health benefits may offset the moderate cost.
However, even in these cases, the limited bioavailability of baicalein remains a significant factor limiting overall value. Future developments in delivery systems to enhance bioavailability may significantly improve the value proposition of baicalein supplements, potentially justifying higher costs if they can demonstrate proportionally increased bioavailability and efficacy in human studies.
Stability Information
Shelf Life
Purified baicalein in powder form, when properly stored, typically has a shelf life of 2-3 years. In standardized Scutellaria extracts, the shelf life is generally 1-2 years, depending on the specific formulation and storage conditions. Liquid formulations containing baicalein tend to have shorter shelf lives of approximately 1 year due to increased potential for oxidation and degradation. Novel formulations such as liposomal or nanoparticle preparations may have different stability profiles and should be evaluated on a case-by-case basis.
The shelf life can be significantly reduced by improper storage conditions, particularly exposure to heat, light, moisture, or oxygen.
Storage Recommendations
Purified baicalein powder should be stored in airtight, opaque containers protected from light, heat, moisture, and oxygen. Optimal storage temperature is between 2-8°C (refrigerated), though room temperature storage (15-25°C) is acceptable for short periods if humidity is controlled. Desiccants should be used in the container to minimize moisture exposure. For standardized Scutellaria extracts containing baicalein, storage in tightly sealed, opaque containers at room temperature (15-25°C) away from direct sunlight is generally sufficient.
Liquid formulations may require refrigeration after opening to prevent oxidation and microbial growth. Freeze-thaw cycles should be avoided for all formulations as they can accelerate degradation. For long-term storage of research-grade material, storage at -20°C under inert gas (nitrogen or argon) is recommended. Once a container is opened, it’s advisable to use the product within 6 months, even if the overall shelf life is longer, as exposure to air accelerates oxidation.
Degradation Factors
Oxidation: Baicalein is susceptible to oxidation due to its multiple hydroxyl groups, particularly in the presence of oxygen, light, or catalytic metal ions, Light exposure: UV and visible light can accelerate the degradation of baicalein through photo-oxidation processes, Heat: Temperatures above 40°C significantly accelerate degradation through multiple mechanisms, Moisture: High humidity environments can promote hydrolysis and may facilitate microbial growth in formulations, Alkaline pH: Baicalein is more stable in slightly acidic to neutral conditions (pH 5-7) and may degrade more rapidly in alkaline environments, Metal ions: Certain metal ions, particularly iron and copper, can catalyze oxidative degradation, Microbial contamination: Certain microorganisms can enzymatically degrade baicalein, Enzymatic degradation: Exposure to specific enzymes, particularly oxidases, can accelerate degradation, Incompatible excipients: Some pharmaceutical excipients may interact with baicalein and reduce stability, Freeze-thaw cycles: Repeated freezing and thawing can disrupt the physical structure of formulations and accelerate chemical degradation
Sourcing
Synthesis Methods
- Extraction from Scutellaria baicalensis root using ethanol, methanol, or acetone solvents
- Purification through column chromatography, typically using silica gel or macroporous resins
- High-performance liquid chromatography (HPLC) for final purification to pharmaceutical grade
- Chemical synthesis from chrysin or other flavonoid precursors (less common, primarily for research)
- Semi-synthetic methods starting from other flavonoids (less common, primarily for research)
- Enzymatic conversion of baicalin to baicalein using β-glucuronidase
- Biotechnological approaches using plant cell cultures (emerging method, not yet commercially viable)
- Microbial transformation using specific bacterial or fungal strains (experimental approach)
Natural Sources
- Scutellaria baicalensis (Huang Qin, Chinese Skullcap) root – primary and most concentrated natural source, containing approximately 5-20% baicalein and baicalin combined
- Scutellaria lateriflora (American Skullcap) – contains lower concentrations compared to S. baicalensis
- Oroxylum indicum (Indian Trumpet Tree) seeds and bark – significant source in traditional Indian medicine
- Thymus vulgaris (Thyme) – contains trace amounts
- Plantago major (Common Plantain) – contains trace amounts
- Scutellaria galericulata (Common Skullcap) – contains lower concentrations compared to S. baicalensis
- Not found in significant amounts in common food sources
Quality Considerations
The quality and potency of baicalein products are influenced by numerous factors throughout the sourcing and production process. The geographical origin of Scutellaria plants significantly impacts baicalein content, with plants from northern China (particularly Hebei and Inner Mongolia provinces) traditionally considered superior. Cultivation conditions, including soil quality, climate, and harvesting time, also affect baicalein concentration, with roots harvested from 3-4 year old plants typically containing optimal levels. Post-harvest processing is crucial, as improper drying or storage can lead to degradation of baicalein. The extraction method dramatically influences both yield and purity, with optimized ethanol extraction followed by column chromatography generally providing the best balance of yield and quality. For standardized extracts, the baicalein content should be verified using validated analytical methods such as HPLC or LC-MS, with reputable suppliers providing certificates of analysis. Potential contaminants to screen for include pesticide residues, heavy metals (particularly cadmium and lead), microbial contamination, and mycotoxins. For research or pharmaceutical applications, purity of ≥98% is typically required, while dietary supplements often contain standardized extracts with 5-20% baicalein content. The stability of baicalein in finished products should be verified through accelerated stability testing, as it can degrade under certain conditions, particularly in the presence of light, heat, and oxygen. Third-party testing by independent laboratories provides additional quality assurance. When evaluating baicalein products, consumers and researchers should prioritize those from manufacturers who implement Good Manufacturing Practices (GMP) and provide transparent information about sourcing, extraction methods, standardization processes, and quality control measures. Additionally, the presence of other bioactive compounds from Scutellaria, particularly baicalin and wogonin, should be considered, as these may contribute to the overall efficacy of the product through synergistic effects.
Historical Usage
While baicalein itself was not specifically identified or isolated until modern times, its primary source, Scutellaria baicalensis (Huang Qin or Chinese Skullcap), has a rich history spanning over 2,000 years in traditional Chinese medicine (TCM). Scutellaria baicalensis was first documented in the Shennong Ben Cao Jing (Divine Farmer’s Materia Medica), one of the earliest Chinese pharmacopeias compiled around 200-250 CE. In this ancient text, Huang Qin was classified as a superior herb for ‘clearing heat and drying dampness,’ particularly from the upper body and lung regions. Traditionally, Scutellaria baicalensis root was primarily used to treat ‘heat’ conditions, which in modern terms would include various inflammatory and infectious diseases.
It was commonly prescribed for fever, cough with thick yellow phlegm, jaundice, diarrhea, dysentery, bleeding disorders, and inflammatory skin conditions. The root was typically prepared as a decoction (tea) or powder, often combined with other herbs in complex formulations tailored to specific conditions. In TCM theory, Huang Qin was considered to have bitter and cold properties, entering primarily the lung, gallbladder, large intestine, small intestine, and stomach meridians. It was valued for its ability to clear heat, remove toxicity, stop bleeding, and calm the fetus during pregnancy.
Beyond China, Scutellaria species were used in traditional medicine systems across East Asia, including in Korean, Japanese, and Mongolian medicine, though specific applications varied by region and cultural context. In Japanese Kampo medicine, Scutellaria baicalensis (Ogon in Japanese) was an important component of formulations such as Sho-saiko-to (Xiao Chai Hu Tang in Chinese), used for liver diseases and inflammatory conditions. In traditional Russian and Eastern European medicine, other Scutellaria species, particularly Scutellaria lateriflora (American skullcap), were used for their calming and sedative properties, though these species contain lower concentrations of baicalein compared to S. baicalensis.
In India, Oroxylum indicum, another plant containing significant amounts of baicalein, has been used in Ayurvedic medicine for respiratory disorders, inflammation, and as a tonic. In modern times, scientific research began to focus on identifying the active compounds in Scutellaria baicalensis, leading to the isolation and characterization of baicalein in the early 20th century. This research revealed that baicalein is one of the primary bioactive compounds responsible for many of the traditional uses of Scutellaria, particularly its anti-inflammatory, antipyretic, and antimicrobial effects. Today, while whole Scutellaria root and its extracts remain widely used in traditional and integrative medicine practices, purified baicalein represents a bridge between traditional herbal medicine and modern pharmacological approaches, embodying the ongoing evolution of traditional knowledge through scientific investigation.
Scientific Evidence
Evidence Rating
Key Studies
Meta Analyses
No formal meta-analyses specifically focused on baicalein in human clinical trials have been published to date. Most systematic reviews and meta-analyses have examined Scutellaria baicalensis preparations in general, which contain baicalein along with other bioactive compounds., A preclinical systematic review and meta-analysis published in 2025 (Chong et al., BMC Gastroenterology) examined the effects of baicalin (the glucuronide metabolite of baicalein) in animal models of ulcerative colitis, finding significant benefits across multiple inflammatory and oxidative stress markers. While this study focused on baicalin rather than baicalein, it provides relevant insights given the metabolic relationship between these compounds.
Ongoing Trials
Several clinical trials investigating baicalein and Scutellaria baicalensis extracts are ongoing, primarily in China, for conditions including viral infections, inflammatory disorders, and cancer., Research is actively exploring novel delivery systems to improve the bioavailability of baicalein, including nanoparticle formulations, liposomal encapsulation, and structural modifications., Preclinical research continues to investigate baicalein’s potential in neurodegenerative diseases, metabolic disorders, and as an adjunct to conventional cancer therapies., Studies examining the synergistic effects of baicalein with other natural compounds and conventional medications are underway, aiming to develop more effective therapeutic combinations.
Disclaimer: The information provided is for educational purposes only and is not intended as medical advice. Always consult with a healthcare professional before starting any supplement regimen, especially if you have pre-existing health conditions or are taking medications.