Norwogonin is a powerful flavone found in Chinese skullcap (Scutellaria baicalensis) that provides exceptional antioxidant and anticancer benefits. This specialized plant compound, distinguished by its unique tri-hydroxyl structure with hydroxyl groups at positions 5, 7, and 8, offers potent protection against cellular damage, helps inhibit cancer cell growth particularly in breast cancer, reduces inflammation through multiple pathways, provides neuroprotective benefits, supports liver health, demonstrates antimicrobial and antiviral properties, provides immune system modulation, and shows strong antioxidant activity while working synergistically with other skullcap compounds to enhance overall health effects.
Alternative Names: 5,7,8-trihydroxyflavone, 5,7,8-Trihydroxy-2-phenyl-4H-chromen-4-one, Scutellaria flavone
Categories: Flavonoid, Phytochemical, Flavone
Primary Longevity Benefits
- Anti-inflammatory
- Antioxidant
- Anticancer
- Neuroprotective
Secondary Benefits
- Hepatoprotective
- Antimicrobial
- Antiviral
- Immunomodulatory
Mechanism of Action
Norwogonin (5,7,8-trihydroxyflavone) exerts its biological effects through multiple molecular pathways, though it is less extensively studied than other flavonoids from Scutellaria baicalensis such as baicalein, baicalin, and wogonin. As an anti-inflammatory agent, norwogonin inhibits the nuclear factor-kappa B (NF-κB) signaling pathway, preventing the expression of pro-inflammatory genes and the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). It also suppresses the activity of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), further reducing inflammatory responses. Norwogonin’s antioxidant properties are primarily attributed to its tri-hydroxyl structure, which enables direct scavenging of reactive oxygen species (ROS) and free radicals.
The presence of three hydroxyl groups at positions 5, 7, and 8 of the flavone structure provides norwogonin with strong electron-donating capabilities, allowing it to neutralize free radicals effectively. Additionally, norwogonin may enhance endogenous antioxidant defense systems by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, leading to increased expression of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). In cancer cells, norwogonin demonstrates anticancer potential through multiple mechanisms. It induces apoptosis by modulating the expression of Bcl-2 family proteins, activating caspases, and promoting mitochondrial membrane permeabilization.
Norwogonin also inhibits cancer cell proliferation by arresting the cell cycle, potentially at the G2/M phase, through regulation of cyclins and cyclin-dependent kinases. Furthermore, it may suppress cancer cell migration and invasion by inhibiting matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT). Norwogonin’s neuroprotective effects are mediated through its antioxidant and anti-inflammatory properties, which help protect neurons from oxidative stress and neuroinflammation. It may also modulate neurotransmitter systems, though the specific mechanisms are less well-characterized compared to other Scutellaria flavonoids.
In the liver, norwogonin exhibits hepatoprotective effects by reducing oxidative stress, inhibiting inflammatory responses, and potentially modulating liver enzyme activities. It may also protect against drug-induced liver injury through these mechanisms. Norwogonin serves as a biosynthetic precursor to wogonin in plants, where it undergoes O-methylation at the 8-position by the enzyme 8-O-methyltransferase. This relationship in the flavonoid biosynthetic pathway may contribute to some shared biological activities between these compounds.
Additionally, norwogonin may possess antimicrobial and antiviral properties, potentially by disrupting microbial membranes and interfering with viral replication processes, though these mechanisms require further investigation.
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.
Norwogonin is rarely available as an isolated supplement, and optimal dosage ranges have not been established through human clinical trials. It is typically consumed as a component of Scutellaria baicalensis (Chinese skullcap) extracts, which contain multiple flavonoids including norwogonin in small amounts (typically less than 1%). Standard dosages for Scutellaria extracts range from 300-900 mg daily.
By Condition
| Condition | Dosage | Notes |
|---|---|---|
| Inflammation | 400-800 mg of standardized Scutellaria extract daily (containing trace amounts of norwogonin) | Efficacy is likely due to the combined action of multiple flavonoids in the extract, not just norwogonin |
| Antioxidant support | 300-600 mg of standardized Scutellaria extract daily | The tri-hydroxyl structure of norwogonin contributes to the overall antioxidant activity of the extract |
| Liver protection | 400-800 mg of standardized Scutellaria extract daily | Often used in combination with other hepatoprotective herbs or compounds |
| Neuroprotection | 500-900 mg of standardized Scutellaria extract daily | Higher doses may be required for crossing the blood-brain barrier in sufficient quantities |
By Age Group
| Age Group | Dosage | Notes |
|---|---|---|
| Adults (18-65) | 300-900 mg of standardized Scutellaria extract daily | Start with lower doses and gradually increase as needed |
| Seniors (65+) | 200-600 mg of standardized Scutellaria extract daily | Lower doses recommended due to potential changes in metabolism and elimination |
| Children and adolescents | Not recommended | Safety and efficacy not established in pediatric populations |
Bioavailability
Absorption Rate
The bioavailability of norwogonin has not been extensively studied in humans. Based on limited animal studies and data from structurally similar flavonoids, norwogonin likely has poor oral bioavailability (estimated at less than 5%) due to its limited water solubility, extensive first-pass metabolism in the liver, and potential efflux by intestinal transporters such as P-glycoprotein.
Enhancement Methods
Combination with piperine (black pepper extract) to inhibit P-glycoprotein efflux and intestinal metabolism, Liposomal encapsulation to improve solubility and intestinal absorption, Nanoparticle formulations to enhance cellular uptake and tissue distribution, Phospholipid complexation to improve lipid solubility and membrane permeability, Co-administration with other flavonoids from Scutellaria that may compete for metabolic enzymes, Cyclodextrin inclusion complexes to improve solubility, Emulsion-based delivery systems to enhance dissolution rate
Timing Recommendations
As norwogonin is typically consumed as part of Scutellaria extracts rather than as an isolated compound, timing recommendations follow those for Scutellaria supplementation. These extracts are best absorbed when taken with meals containing some fat, which can enhance solubility and absorption of flavonoids including norwogonin. Taking divided doses throughout the day may maintain more consistent blood levels due to the relatively short half-life of flavonoids (approximately 2-4 hours in animal studies). For anti-inflammatory effects, consistent daily dosing is recommended to maintain therapeutic levels.
The presence of other flavonoids in Scutellaria extracts may influence the absorption and metabolism of norwogonin through competitive inhibition of metabolic enzymes or transporters.
Safety Profile
Safety Rating
Side Effects
- Limited data on isolated norwogonin; side effects are primarily based on Scutellaria extracts containing norwogonin
- Gastrointestinal discomfort (mild to moderate)
- Nausea (uncommon)
- Diarrhea (uncommon)
- Headache (rare)
- Dizziness (rare)
- Potential sedative effects at higher doses
- Allergic reactions (rare)
Contraindications
- Pregnancy and breastfeeding (due to insufficient safety data)
- Scheduled surgery (discontinue 2 weeks before due to potential anticoagulant effects of flavonoids)
- Bleeding disorders (due to potential antiplatelet activity of flavonoids)
- Hormone-sensitive conditions (due to potential phytoestrogenic effects of some flavonoids)
- Autoimmune conditions (caution due to immunomodulatory effects)
- Hypotension (may enhance blood pressure-lowering effects)
Drug Interactions
- Anticoagulant and antiplatelet medications (may enhance bleeding risk)
- Sedatives and CNS depressants (may enhance sedative effects)
- Cytochrome P450 substrates (flavonoids may affect metabolism of drugs metabolized by CYP1A2, CYP2C9, and CYP3A4)
- P-glycoprotein substrates (may alter drug transport and absorption)
- Immunosuppressants (may interfere with therapeutic effects)
- Antihypertensive medications (may enhance blood pressure-lowering effects)
- Hepatotoxic drugs (potential for interactions affecting liver function)
Upper Limit
Due to limited human clinical data on isolated norwogonin, a definitive upper limit has not been established. Safety considerations are based on Scutellaria extracts, which contain norwogonin as a minor component. For Scutellaria extracts, doses exceeding 1000 mg daily are not recommended without medical supervision.
Regulatory Status
Fda Status
Norwogonin itself is not approved as a drug by the FDA and is not commonly available as an isolated supplement. Scutellaria baicalensis extracts containing norwogonin are regulated as dietary supplements under the Dietary Supplement Health and Education Act (DSHEA) of 1994. Manufacturers cannot make specific disease treatment claims but may make general structure/function claims with appropriate disclaimers. The FDA has not evaluated the safety or efficacy of norwogonin specifically.
International Status
Eu: In the European Union, norwogonin is not approved as a medicinal product. Scutellaria baicalensis extracts containing norwogonin may be sold as food supplements, subject to the general food safety regulations. The European Food Safety Authority (EFSA) has not issued specific health claims for norwogonin or Scutellaria extracts. Some EU member states may have their own regulations regarding traditional herbal medicinal products containing Scutellaria.
Canada: Health Canada regulates Scutellaria baicalensis extracts containing norwogonin as Natural Health Products (NHPs). Several Scutellaria products have been issued Natural Product Numbers (NPNs), allowing them to be sold with specific health claims related to traditional use in Chinese medicine. Isolated norwogonin is not specifically approved as a standalone ingredient.
Australia: The Therapeutic Goods Administration (TGA) regulates Scutellaria baicalensis extracts as complementary medicines. Several products containing these extracts are listed on the Australian Register of Therapeutic Goods (ARTG). Traditional use claims are permitted with appropriate evidence of traditional use in Chinese medicine. Norwogonin as an isolated compound is not specifically regulated.
China: Scutellaria baicalensis (Huang Qin) is officially listed in the Chinese Pharmacopoeia as a traditional Chinese medicine. Various formulations containing this herb are approved for specific indications based on traditional use and modern research. Norwogonin as an isolated compound is primarily used in research rather than as an approved therapeutic agent.
Japan: Scutellaria baicalensis is included in the Japanese Pharmacopoeia and is a component of several Kampo medicine formulations approved by the Ministry of Health, Labour and Welfare for specific indications. Norwogonin as an isolated compound is not specifically regulated for therapeutic use.
Synergistic Compounds
| Compound | Synergy Mechanism | Evidence Rating |
|---|---|---|
| Baicalein | Both are flavones from Scutellaria baicalensis with complementary antioxidant structures. Baicalein (5,6,7-trihydroxyflavone) and norwogonin (5,7,8-trihydroxyflavone) differ only in the position of one hydroxyl group, potentially providing broader antioxidant coverage when combined. | 3 |
| Baicalin | The glycoside form of baicalein, works synergistically with norwogonin in modulating inflammatory pathways and enhancing antioxidant defense systems. May also improve bioavailability of norwogonin through competitive inhibition of metabolic enzymes. | 3 |
| Wogonin | Wogonin is biosynthetically derived from norwogonin through O-methylation at the 8-position. The combination provides complementary biological activities, with norwogonin offering stronger antioxidant effects and wogonin providing enhanced anti-inflammatory and anticancer properties. | 3 |
| Oroxylin A | Like wogonin, oroxylin A is derived from norwogonin through methylation (at the 6-position). The combination provides complementary effects on various signaling pathways involved in inflammation and cellular protection. | 3 |
| Piperine | Enhances norwogonin’s bioavailability by inhibiting P-glycoprotein efflux and intestinal metabolism, potentially increasing plasma concentrations. | 2 |
| Quercetin | Complementary antioxidant and anti-inflammatory effects. May compete for metabolic enzymes, potentially extending norwogonin’s half-life. | 2 |
| Vitamin C | May help regenerate norwogonin after it acts as an antioxidant, extending its antioxidant capacity through redox cycling. | 2 |
| Vitamin E | Complementary antioxidant that protects lipid membranes, while norwogonin acts more in the aqueous phase, providing broader antioxidant protection. | 2 |
| N-acetylcysteine | Enhances glutathione production, which may work synergistically with norwogonin’s direct antioxidant effects for comprehensive cellular protection against oxidative stress. | 2 |
Antagonistic Compounds
| Compound | Interaction Type | Evidence Rating |
|---|---|---|
| Iron supplements | Norwogonin, like other flavonoids with multiple hydroxyl groups, may chelate iron, potentially reducing its absorption when taken simultaneously. | 2 |
| Anticoagulant and antiplatelet medications | Norwogonin may enhance the anticoagulant effects of these medications, potentially increasing bleeding risk, though specific studies on norwogonin are limited. | 2 |
| Cytochrome P450 substrates | Norwogonin may inhibit certain CYP enzymes, potentially affecting the metabolism of drugs that are substrates for these enzymes, though specific data on norwogonin’s effects on CYP enzymes is limited. | 2 |
| P-glycoprotein substrates | Norwogonin may inhibit P-glycoprotein, potentially altering the transport and absorption of drugs that are P-gp substrates. | 2 |
| Pro-oxidant compounds | Certain conditions or high doses may cause norwogonin to exhibit pro-oxidant effects, potentially interacting negatively with other pro-oxidant compounds. | 2 |
| Immunosuppressive drugs | Norwogonin’s potential immunomodulatory effects may interfere with the therapeutic action of immunosuppressants, though specific studies are lacking. | 1 |
| Sedatives and CNS depressants | If norwogonin shares the GABA-modulating effects observed with other Scutellaria flavonoids, it may potentiate the effects of sedatives. | 1 |
| Antihypertensive medications | Norwogonin may enhance blood pressure-lowering effects, potentially leading to hypotension, though specific studies are lacking. | 1 |
Cost Efficiency
Relative Cost
High (as isolated compound) / Medium (as part of Scutellaria extracts)
Cost Per Effective Dose
Isolated norwogonin is rarely available commercially for supplementation and is primarily sold as a research chemical at prices ranging from $300-$800 per 10-25 mg, making it prohibitively expensive for regular supplementation. Standardized Scutellaria baicalensis extracts containing small amounts of norwogonin along with other flavonoids typically cost $0.50-$2.00 per day for basic extracts and $2.00-$5.00 per day for premium, highly standardized formulations.
Value Analysis
The cost-effectiveness of norwogonin must be evaluated in the context of Scutellaria extracts, as isolated norwogonin is not practically available for regular supplementation due to its high cost and limited commercial availability. Scutellaria extracts offer reasonable value for their antioxidant and anti-inflammatory benefits, with the therapeutic effects resulting from the combined action of multiple flavonoids including baicalin, baicalein, wogonin, and norwogonin. The contribution of norwogonin specifically to the overall value of these extracts is difficult to quantify but is likely significant due to its potent antioxidant properties derived from its tri-hydroxyl structure. For research purposes, the high cost of pure norwogonin is justified for controlled studies investigating its specific mechanisms and effects.
For consumers seeking health benefits, standardized Scutellaria extracts represent a more practical and cost-effective approach to obtaining norwogonin along with complementary flavonoids. Premium extracts with enhanced bioavailability may offer better value despite their higher price point due to improved absorption and utilization of the active compounds. When comparing the cost-effectiveness of Scutellaria extracts to other antioxidant and anti-inflammatory supplements, they generally offer competitive value, particularly when the broad spectrum of biological activities is considered.
Stability Information
Shelf Life
Pure norwogonin is relatively unstable due to its tri-hydroxyl structure, which makes it susceptible to oxidation. When properly stored, isolated norwogonin may maintain stability for 1-2 years. Standardized Scutellaria extracts containing norwogonin typically have a shelf life of 2 years from the date of manufacture.
Storage Recommendations
Store in a cool, dry place away from direct sunlight in airtight, opaque containers. Refrigeration is recommended for pure norwogonin and can extend shelf life of extracts containing norwogonin. Protect from moisture, heat, oxygen, and light exposure, which can accelerate degradation. For research-grade pure norwogonin, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability.
Antioxidant preservatives may be added to commercial formulations to enhance stability.
Degradation Factors
Exposure to UV light and sunlight – causes rapid photodegradation due to the reactive hydroxyl groups, High temperatures (above 25°C) – accelerates oxidation and decomposition, Moisture – can promote hydrolysis and microbial growth, Oxygen exposure – leads to oxidation, particularly of the hydroxyl groups at positions 7 and 8, pH extremes – norwogonin is most stable at slightly acidic pH (5-6), Metal ions (particularly iron and copper) – can catalyze oxidation reactions, Enzymatic activity – may occur in improperly processed plant extracts, Repeated freeze-thaw cycles – can accelerate degradation
Sourcing
Synthesis Methods
- Semi-synthetic methods starting from other flavonoids such as chrysin
- Total chemical synthesis through chalcone intermediates followed by cyclization and hydroxylation
- Enzymatic conversion of related flavonoids
- Biotechnological production using engineered microorganisms or plant cell cultures
Natural Sources
- Scutellaria baicalensis (Chinese skullcap) root – primary source, containing small amounts (typically less than 1%) of norwogonin
- Scutellaria lateriflora (American skullcap) – contains trace amounts
- Scutellaria barbata – contains varying amounts
- Oroxylum indicum – may contain small amounts
Quality Considerations
Norwogonin is rarely available as an isolated compound for supplementation and is typically consumed as part of Scutellaria baicalensis extracts. When selecting Scutellaria extracts that contain norwogonin, look for products that are standardized to contain specific percentages of total flavonoids, verified by HPLC analysis. High-quality extracts should provide third-party testing results confirming the flavonoid content and purity. Scutellaria baicalensis extracts should be sourced from mature roots (at least 3-4 years old) as these contain higher concentrations of active flavonoids. Organic cultivation is preferred to minimize pesticide residues. Extraction methods significantly impact quality – alcohol-water extractions typically preserve more of the active compounds than water-only extractions. Avoid products with artificial fillers, preservatives, or excessive excipients. For research purposes, high-purity isolated norwogonin (>95%) is available from specialized chemical suppliers, though at significant cost due to the challenges in isolation and purification.
Historical Usage
Norwogonin itself was not identified or isolated until modern times, but it is a constituent of Scutellaria baicalensis (Huang Qin or Chinese skullcap), which has been used in traditional Chinese medicine (TCM) for over 2,000 years. While the specific contribution of norwogonin to the traditional uses of Scutellaria was unknown to ancient practitioners, it is now recognized as one of the bioactive compounds in this historically important medicinal plant. In TCM, Scutellaria baicalensis root is classified as a cooling herb that clears heat, dries dampness, and eliminates toxins. It was traditionally used to treat fevers, inflammation, respiratory infections, diarrhea, jaundice, and bleeding disorders.
The herb appears in numerous classical TCM formulations, including Huang-Lian-Jie-Du-Tang and Xiao-Chai-Hu-Tang, which are still used today. The first documented medicinal use of Scutellaria baicalensis appears in the Shennong Bencao Jing (Divine Farmer’s Materia Medica), compiled around 200-250 CE, where it was recommended for treating abscesses, sores, and inflammatory conditions. During the Ming Dynasty (1368-1644 CE), the famous physician Li Shizhen included detailed descriptions of Scutellaria baicalensis in his monumental work, the Compendium of Materia Medica (Bencao Gangmu), noting its effectiveness for ‘clearing heat from the upper burner’ and treating coughs with yellow phlegm, thirst, and irritability. In Japanese Kampo medicine, which evolved from TCM, Scutellaria baicalensis (called Ogon) is a component of important formulations such as Sho-saiko-to, used for liver disorders.
In Korean traditional medicine, the herb (known as Hwanggeumgol) was used similarly to its applications in China. Norwogonin was first isolated and characterized in the mid-20th century as part of the scientific investigation into the active components of Scutellaria species. It was identified as a precursor in the biosynthetic pathway leading to the formation of wogonin and oroxylin A, two other important flavonoids in Scutellaria. Modern scientific interest in norwogonin began to grow in the late 20th and early 21st centuries as research revealed its antioxidant, anti-inflammatory, and potential anticancer properties.
While norwogonin is present in smaller amounts than other flavonoids in Scutellaria, its unique tri-hydroxyl structure and position in the flavonoid biosynthetic pathway have made it an interesting subject for pharmacological research.
Scientific Evidence
Evidence Rating
Key Studies
Meta Analyses
No meta-analyses specifically on norwogonin are currently available; most analyses focus on Scutellaria baicalensis extracts containing multiple flavonoids including norwogonin as a minor component.
Ongoing Trials
Limited ongoing trials specifically investigating norwogonin; most research focuses on Scutellaria extracts or other major flavonoids, Some preclinical research exploring norwogonin’s potential in inflammatory conditions and cancer models, Investigations into the structure-activity relationships of Scutellaria flavonoids including norwogonin
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.