Named Bioactive Compounds · Compound
Tangeretin (Flavone)
Moderate Evidenceflavonoid
Hermetica Superfood Encyclopedia
Tangeretin is a polymethoxyflavone found primarily in citrus peels that exhibits anti-inflammatory activity by inhibiting nuclear factor-kappa B (NF-κB) signaling. This flavone demonstrates potential neuroprotective and cholesterol-lowering effects through modulation of cellular oxidative stress pathways.
Tangeretin is a pentamethoxyflavone (C20H20O7) naturally occurring in the peels of tangerines (Citrus reticulata), sweet oranges, and mandarins. It is extracted from citrus peels using column chromatography or supercritical extraction methods, achieving >95% purity.
No human clinical trials, randomized controlled trials, or meta-analyses for tangeretin were identified in the research. Available evidence is limited to in vitro cell culture studies, rat pharmacokinetic assessments, and other preclinical investigations examining anti-inflammatory, anti-proliferative, neuroprotective, and cholesterol-lowering effects.
No clinically studied human dosage ranges are available. Preclinical rat studies used oral doses of 50 mg/kg and intravenous doses of 5 mg/kg for pharmacokinetic assessment. Consult a healthcare provider before starting any new supplement.
Tangeretin (5,6,7,8,4'-pentamethoxyflavone) is a polymethoxylated flavone, not a nutritional food source, so traditional macronutrient profiling (protein, fat, carbohydrate, fiber) is not applicable. It is a bioactive secondary metabolite found primarily in the peel (flavedo) of tangerines and other citrus fruits (Citrus reticulata, C. sinensis). Key details: • Molecular formula: C20H20O7; Molecular weight: 372.37 g/mol. • Natural concentration in citrus peel: approximately 0.1–2.0 mg/g dry weight of tangerine peel; trace amounts (<0.01 mg/g) in citrus juice. • Classification: Polymethoxylated flavone (PMF), distinguished from hydroxylated flavones by its five methoxy groups, which significantly increase lipophilicity (log P ~2.5–3.0). • Bioavailability notes: Oral bioavailability in humans is considered low due to poor aqueous solubility (~0.3 µg/mL in water), extensive first-pass metabolism via CYP1A2 and CYP3A4-mediated demethylation, and rapid glucuronidation/sulfation. Lipophilic formulations, nanoencapsulation, or co-administration with P-glycoprotein inhibitors may enhance absorption. In rat models, peak plasma concentrations after oral dosing (50 mg/kg) reach approximately 1–3 µM. • Primary metabolites include 4'-demethyltangeretin (major phase I metabolite) and various glucuronide/sulfate conjugates (phase II). • Co-occurring PMFs in citrus peel that may have synergistic activity: nobiletin (3',4',5,6,7,8-hexamethoxyflavone), sinensetin, and heptamethoxyflavone. • Contains no significant vitamins, minerals, protein, fiber, or caloric value when used as an isolated compound. • Typical research/supplement doses studied in preclinical models range from 10–100 mg/kg body weight (animal studies); no established human dietary reference intake or recommended dose exists. • The compound is GRAS (Generally Recognized as Safe) as a component of citrus extracts in food, but isolated supplement-grade tangeretin lacks formal regulatory dosing guidelines.
Tangeretin exerts its effects primarily through inhibition of the nuclear factor-kappa B (NF-κB) inflammatory pathway and cyclooxygenase-2 (COX-2) enzyme activity. The compound also activates peroxisome proliferator-activated receptor alpha (PPAR-α), which regulates lipid metabolism and may contribute to cholesterol reduction. Additionally, tangeretin demonstrates antioxidant activity by scavenging reactive oxygen species and enhancing cellular glutathione levels.
Current evidence for tangeretin is limited to in vitro and animal studies, with no published human clinical trials. In vitro studies have shown anti-proliferative effects against various cancer cell lines at concentrations of 10-100 μM. Animal studies using doses of 5-20 mg/kg body weight demonstrated neuroprotective effects in models of neurodegeneration and cognitive decline. Cholesterol-lowering effects have been observed in rodent studies, but human efficacy remains unestablished.
Tangeretin appears well-tolerated in animal studies at therapeutic doses, with no significant adverse effects reported. However, comprehensive safety data in humans is lacking, particularly regarding long-term use and potential drug interactions. The compound may theoretically interact with medications metabolized by cytochrome P450 enzymes, though specific interactions have not been documented. Pregnant and breastfeeding women should avoid tangeretin supplements due to insufficient safety data in these populations.
