Scutellarein

Scutellarein is a flavone compound found in Scutellaria baicalensis that exhibits antioxidant and anti-inflammatory properties through Nrf2/HO-1 pathway activation. It modulates TNFR2 receptors on regulatory T-cells and suppresses VEGF expression, showing potential anti-cancer effects in laboratory studies.

Origin & History

Scutellarein is a flavone compound (C15H10O6) naturally found in plants of the Scutellaria genus, including Chinese skullcap (S. baicalensis) and American skullcap (S. lateriflora). It is typically extracted from plant material using ethanol or methanol solvents, followed by chromatographic purification, yielding a light yellow powder with ≥98% purity.

Historical & Cultural Context

Scutellarein is a minor constituent in Scutellaria species used in Traditional Chinese Medicine for over 1,000 years, particularly S. baicalensis (Huang Qin) for fever and inflammation. Native Americans have used S. lateriflora for anxiety and spasms since the 18th century, though scutellarein was not isolated until its structure was elucidated in 1910.

Health Benefits

• Antioxidant activity through free radical scavenging and Nrf2/HO-1 pathway activation (preclinical evidence only)
• Anti-cancer potential via TNFR2 binding on regulatory T-cells and VEGF suppression (in vitro studies only)
• Neuroprotective effects through estrogen receptor modulation and acetylcholinesterase inhibition (animal models only)
• Anti-HIV activity by blocking gp120-CD4 interactions (cell culture studies only)
• Anti-inflammatory effects via xanthine oxidase and proteasome inhibition (preclinical evidence only)

How It Works

Scutellarein activates the Nrf2/HO-1 antioxidant pathway, enhancing cellular defense against oxidative stress through increased heme oxygenase-1 expression. It selectively binds to TNFR2 receptors on regulatory T-cells, potentially modulating immune responses. The compound also suppresses VEGF (vascular endothelial growth factor) expression, which may inhibit angiogenesis in tumor development.

Scientific Research

No human clinical trials, randomized controlled trials, or meta-analyses have been conducted specifically on scutellarein. Research is limited to preclinical in vitro and animal models, with human studies only available for its glucuronide form, scutellarin (e.g., PMID: 19499850 showing improved neurological scores in 80 stroke patients).

Clinical Summary

Current research on scutellarein is limited to preclinical in vitro and animal studies, with no human clinical trials published to date. Laboratory studies have demonstrated significant free radical scavenging activity with IC50 values ranging from 15-30 μM in various antioxidant assays. In vitro cancer cell studies show growth inhibition rates of 40-60% at concentrations of 50-100 μM across multiple cell lines. The evidence remains preliminary and requires human clinical validation to establish therapeutic efficacy and safety profiles.

Nutritional Profile

Scutellarein (4',5,6-trihydroxyflavone) is a pure bioactive flavone compound, not a whole food ingredient, and therefore does not contain macronutrients (protein, fat, carbohydrates), dietary fiber, vitamins, or minerals in any relevant quantity. Its nutritional characterization is defined entirely by its identity as a single polyphenolic molecule. Molecular weight: 286.24 g/mol. Molecular formula: C15H10O6. It belongs to the flavone subclass of flavonoids, characterized by a 4',5,6-trihydroxylated flavone backbone. Scutellarein is the aglycone form of scutellarin (scutellarein-7-O-glucuronide), and is primarily obtained in vivo through hydrolysis of scutellarin by intestinal microbiota or hepatic enzymes. Natural sources include Scutellaria baicalensis (Chinese skullcap), Scutellaria lateriflora, and Erigeron breviscapus, where it occurs predominantly in glycoside form (scutellarin) at concentrations ranging approximately 0.1–4% dry weight in aerial plant parts. Bioavailability: oral bioavailability of scutellarein as a free aglycone is limited due to poor aqueous solubility (logP approximately 1.9–2.4) and rapid phase II metabolism (glucuronidation and sulfation). Peak plasma concentrations following oral scutellarin administration in rodent models suggest conversion to scutellarein with Tmax of approximately 1–2 hours. Nanoparticle and phospholipid complex formulations have demonstrated enhanced bioavailability in preclinical studies (up to 3–5 fold improvement). No established dietary reference intake or recommended dose exists; experimental in vitro concentrations typically range from 10–100 µM.

Preparation & Dosage

No clinically studied dosages exist for scutellarein due to absence of human trials. Preclinical studies use 10-100 μM in cell cultures or 10-50 mg/kg in rodents, while commercial products suggest 5-50 mg/day without clinical validation. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Baicalein, Baicalin, Quercetin, EGCG, Curcumin

Safety & Interactions

Safety data for scutellarein is extremely limited due to lack of human studies, making it difficult to establish safe dosage ranges or identify potential adverse effects. As a flavone compound, it may interact with cytochrome P450 enzymes, potentially affecting medication metabolism, though specific drug interactions have not been documented. Pregnant and breastfeeding women should avoid scutellarein due to insufficient safety data and potential hormonal effects through estrogen receptor modulation. Individuals with autoimmune conditions should exercise caution given its T-cell regulatory effects.