Oroxylin A

• Anti-inflammatory
• Antioxidant
• Anticancer
• Neuroprotective

• Hepatoprotective
• Anxiolytic
• Antiviral
• Antimicrobial
• Cognitive enhancement

Oroxylin A (OA) exerts its diverse biological effects through multiple molecular pathways. As an anti-inflammatory agent, OA inhibits the nuclear factor-kappa B (NF-κB) signaling pathway by preventing IκB kinase (IKK) activation and subsequent nuclear translocation of NF-κB, thereby reducing the expression of pro-inflammatory genes. It also suppresses the production of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while inhibiting cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. OA’s antioxidant properties are mediated through direct scavenging of reactive oxygen species (ROS) and enhancement of endogenous antioxidant defense systems.

It activates the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, leading to increased expression of antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione S-transferase (GST). In cancer cells, OA demonstrates multiple anticancer mechanisms. It induces apoptosis through both intrinsic (mitochondrial) and extrinsic (death receptor) pathways by modulating the expression of Bcl-2 family proteins, activating caspases, and promoting cytochrome c release from mitochondria. OA inhibits cancer cell proliferation by arresting the cell cycle at G2/M phase through regulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and p21.

It also suppresses cancer cell migration and invasion by inhibiting matrix metalloproteinases (MMPs) and epithelial-mesenchymal transition (EMT). Additionally, OA has been shown to reverse multidrug resistance in cancer cells by inhibiting P-glycoprotein (P-gp) expression and function. In the central nervous system, OA exhibits neuroprotective effects through multiple mechanisms. It enhances gamma-aminobutyric acid (GABA) signaling by acting as a positive allosteric modulator of GABA-A receptors, contributing to its anxiolytic properties.

OA protects neurons from oxidative stress and excitotoxicity by reducing glutamate-induced calcium influx and maintaining mitochondrial function. It also promotes neurogenesis and synaptic plasticity by enhancing brain-derived neurotrophic factor (BDNF) expression and activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In the liver, OA demonstrates hepatoprotective effects by inhibiting hepatic stellate cell (HSC) activation and reducing collagen production, thereby attenuating liver fibrosis. It also enhances liver regeneration by promoting hepatocyte proliferation through activation of the Wnt/β-catenin signaling pathway.

Furthermore, OA exhibits antimicrobial properties by disrupting bacterial cell membranes and inhibiting viral replication through interference with viral attachment and entry processes. Its cognitive-enhancing effects are attributed to inhibition of acetylcholinesterase (AChE) activity, resulting in increased acetylcholine levels in the synaptic cleft, and modulation of glutamatergic neurotransmission through N-methyl-D-aspartate (NMDA) receptors.

Due to limited human clinical trials specifically on isolated Oroxylin A, optimal dosage ranges are not well established. Most studies use Scutellaria baicalensis or Oroxylum indicum extracts standardized to contain 1-5% Oroxylin A, with typical daily doses ranging from 300-900 mg of the extract.

Oroxylin A has poor oral bioavailability, estimated at approximately 2-7% in animal studies, primarily due to its low water solubility, extensive first-pass metabolism in the liver, and efflux by P-glycoprotein transporters in the intestine.

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 quercetin or other flavonoids that may compete for metabolic enzymes, Cyclodextrin inclusion complexes to improve solubility, Self-microemulsifying drug delivery systems (SMEDDS) to enhance dissolution rate

Oroxylin A is best absorbed when taken with meals containing some fat, which can enhance solubility and absorption. Taking divided doses throughout the day may maintain more consistent blood levels due to its relatively short half-life (approximately 1-3 hours in animal studies). For anxiety or sleep benefits, taking a dose in the evening may be beneficial due to its GABA-modulating effects. For anti-inflammatory effects, consistent daily dosing is recommended to maintain therapeutic levels.

• Gastrointestinal discomfort (mild to moderate)
• Nausea (uncommon)
• Diarrhea (uncommon)
• Headache (rare)
• Dizziness (rare)
• Potential sedative effects at higher doses
• Allergic reactions (rare)

• Pregnancy and breastfeeding (due to insufficient safety data)
• Scheduled surgery (discontinue 2 weeks before due to potential anticoagulant effects)
• Bleeding disorders (due to potential antiplatelet activity)
• Hormone-sensitive conditions (due to potential phytoestrogenic effects)
• Autoimmune conditions (caution due to immunomodulatory effects)
• Hypotension (may enhance blood pressure-lowering effects)

• Anticoagulant and antiplatelet medications (may enhance bleeding risk)
• Sedatives and CNS depressants (may enhance sedative effects)
• Cytochrome P450 substrates (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 additive effects on liver function)

Due to limited human clinical data, a definitive upper limit has not been established. Based on animal studies and traditional use of Scutellaria baicalensis and Oroxylum indicum, doses exceeding 1000 mg of standardized extract (containing approximately 10-50 mg Oroxylin A) daily are not recommended without medical supervision.

Oroxylin A itself is not approved as a drug by the FDA. Supplements containing Oroxylin A or extracts of Scutellaria baicalensis and Oroxylum indicum 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 Oroxylin A specifically.

Eu: In the European Union, Oroxylin A is not approved as a medicinal product. Scutellaria baicalensis and Oroxylum indicum extracts containing Oroxylin A 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 Oroxylin A or these plant extracts. Some EU member states may have their own regulations regarding traditional herbal medicinal products containing these plants.

Canada: Health Canada regulates Scutellaria baicalensis and Oroxylum indicum extracts containing Oroxylin A as Natural Health Products (NHPs). Several products containing these extracts have been issued Natural Product Numbers (NPNs), allowing them to be sold with specific health claims related to traditional use in Chinese or Ayurvedic medicine. Isolated Oroxylin A is not specifically approved as a standalone ingredient.

Australia: The Therapeutic Goods Administration (TGA) regulates Scutellaria baicalensis and Oroxylum indicum 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 or Ayurvedic medicine.

China: Scutellaria baicalensis (Huang Qin) is officially listed in the Chinese Pharmacopoeia as a traditional Chinese medicine. Oroxylum indicum is recognized in the Chinese Materia Medica. Various formulations containing these herbs are approved for specific indications based on traditional use and modern research. Isolated Oroxylin A is used in research but is not commonly approved as a standalone pharmaceutical.

India: Oroxylum indicum is officially recognized in the Ayurvedic Pharmacopoeia of India. It is a component of several classical Ayurvedic formulations approved for use in traditional Ayurvedic practice. Scutellaria baicalensis is less commonly used in Indian traditional medicine but may be found in some formulations influenced by TCM.

Medium to high

For standardized Scutellaria baicalensis or Oroxylum indicum extracts (typically containing 1-5% Oroxylin A): $0.50-$2.00 per day for basic extracts; $2.00-$5.00 per day for premium, highly standardized, or enhanced bioavailability formulations. Pure isolated Oroxylin A for research purposes is significantly more expensive, ranging from $300-$600 per gram.

The cost-effectiveness of Oroxylin A supplementation varies depending on the intended use and formulation quality. Standard Scutellaria or Oroxylum extracts offer reasonable value for general anti-inflammatory and antioxidant benefits, comparable to other botanical anti-inflammatories like curcumin. However, the relatively low bioavailability of standard formulations may limit therapeutic potential, making enhanced delivery systems (liposomal, nanoparticle, etc.) potentially more cost-effective despite their higher price point. For specific conditions like anxiety, cognitive support, or liver protection, Oroxylin A-containing extracts may offer good value compared to pharmaceutical alternatives, with potentially fewer side effects.

The highest value is likely found in high-quality, standardized extracts that specify exact Oroxylin A content and employ bioavailability-enhancing technologies. These provide more predictable therapeutic effects, justifying their premium price. For research purposes, the cost of pure Oroxylin A is high but necessary for controlled studies. For general consumers seeking health benefits, extracts standardized for total flavonoid content (including Oroxylin A, baicalin, baicalein, and wogonin) may offer the best overall value, as these compounds work synergistically.

Pure Oroxylin A powder is relatively stable for 2-3 years when properly stored. Standardized Scutellaria or Oroxylum extracts typically have a shelf life of 2 years from the date of manufacture.

Store in a cool, dry place away from direct sunlight in airtight containers. Refrigeration can extend shelf life, particularly for liquid formulations. Protect from moisture, heat, and light exposure, which can accelerate degradation. For research-grade pure Oroxylin A, storage under inert gas (nitrogen or argon) at -20°C is recommended for maximum stability.

Exposure to UV light and sunlight – causes photodegradation and structural changes, High temperatures (above 30°C) – accelerates oxidation and decomposition, Moisture – can promote hydrolysis and microbial growth, Oxygen exposure – leads to oxidation of the flavonoid structure, pH extremes – Oroxylin A is most stable at slightly acidic to neutral pH (5-7), Metal ions (particularly iron and copper) – can catalyze oxidation reactions, Enzymatic activity – may occur in improperly processed plant extracts

Synthesis Methods

Natural Sources

Quality Considerations

Oroxylin A is a bioactive flavonoid found primarily in Scutellaria baicalensis (Huang Qin or Chinese skullcap) and Oroxylum indicum (Indian trumpet flower), both of which have been used in traditional medicine systems for centuries. While Oroxylin A itself was not isolated and identified until the modern era, the plants containing it have a rich historical usage. In Traditional Chinese Medicine (TCM), Scutellaria baicalensis root has been used for over 2,000 years and 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. The first documented medicinal use of Scutellaria baicalensis appears in the Shennong Bencao Jing (Divine Farmer’s Materia Medica), compiled around 200-250 CE. Oroxylum indicum, known as ‘Shyonaka’ in Ayurvedic medicine, has been used for over 3,000 years in the Indian subcontinent. In Ayurveda, it is considered to have anti-inflammatory, antimicrobial, and digestive properties.

The bark, seeds, and root bark were traditionally used to treat respiratory conditions, fever, digestive disorders, and rheumatism. It is a component of the famous Ayurvedic formulation ‘Dashamula,’ a ten-root combination used for various inflammatory conditions. In Thai traditional medicine, Oroxylum indicum (called ‘Pheka’) has been used to treat coughs, respiratory infections, and digestive disorders. In Filipino traditional medicine, it is known as ‘Pingka-pingkahan’ and used for similar purposes.

Modern scientific interest in Oroxylin A began in the late 20th century, with its isolation and structural characterization in the 1970s. Research intensified in the 1990s and 2000s as studies revealed its anti-inflammatory, antioxidant, neuroprotective, and potential anticancer properties. Today, Oroxylin A is recognized as one of the bioactive components responsible for many of the therapeutic effects traditionally attributed to Scutellaria baicalensis and Oroxylum indicum, bridging ancient medicinal wisdom with modern pharmacological understanding.

Limited meta-analyses specifically on Oroxylin A; most analyses focus on Scutellaria baicalensis or Oroxylum indicum extracts containing multiple flavonoids including Oroxylin A, baicalin, baicalein, and wogonin.

Several preclinical studies investigating Oroxylin A’s potential in cancer therapy, particularly in combination with conventional chemotherapeutic agents, Research on nanoparticle delivery systems to enhance Oroxylin A’s bioavailability and targeted delivery, Investigations into Oroxylin A’s neuroprotective effects in models of neurodegenerative diseases and cognitive disorders