Nobiletin (Polymethoxylated Flavone · Metabolic Health · Cognitive Support)
| Compound | Nobiletin |
| Chemical class | Polyphenol — Polymethoxylated Flavone (PMF) |
| CAS | 478-01-3 |
| Primary source | Citrus sinensis, Citrus nobilis (sweet orange, mandarin peel) |
| Key applications | Metabolic syndrome, anti-inflammatory, cognitive support |
| Claim strength | Moderate |
| Typical form | PMF-standardised citrus peel extract; isolate |
Name origin: From Citrus nobilis (King mandarin), reflecting its primary botanical source. Nobiletin is a hexamethoxylated flavone — the highest degree of methoxylation among common citrus PMFs. Traditional use: Dried citrus peel preparations (chen pi in TCM; triphala ingredients in Ayurveda) have been prescribed for metabolic, digestive, and respiratory complaints for centuries. Nobiletin is a key constituent in these preparations. Research trajectory: Nobiletin has one of the strongest preclinical evidence bases among citrus PMFs, with documented activities in metabolic syndrome, adipogenesis, cognitive function, and inflammation. Small human studies are beginning to emerge. Commercial source: Supplied in PMF-standardised citrus peel extracts; concentrated nobiletin isolates (≥98%) are available from specialist suppliers.
Evidence for Nobiletin Applications
Metabolic syndrome and adipogenesis: Nobiletin activates AMPK and PPAR-α pathways, reducing adipocyte differentiation, improving insulin sensitivity, and lowering serum triglycerides in animal models of diet-induced obesity. A small human crossover study in metabolic syndrome subjects found PMF-rich citrus extract (nobiletin-containing) reduced visceral adiposity markers. Claim strength: Moderate.
Anti-inflammatory and NF-κB suppression: Nobiletin inhibits NF-κB, AP-1, and MAPK signalling across macrophage, epithelial, and synovial cell models. In vivo animal models confirm anti-inflammatory efficacy in colitis, lung injury, and arthritis. The hexamethoxy structure confers superior intracellular access versus hydroxylated flavonoids. Claim strength: Moderate.
Cognitive and neuroprotective activity: Nobiletin crosses the blood-brain barrier readily. Animal studies document improved memory consolidation, reduced amyloid-beta deposition, and protection against dopaminergic neuron loss. Nobiletin activates ERK and CREB signalling relevant to synaptic plasticity. Human clinical data are emerging but limited. Claim strength: Moderate (preclinical convergent; early human).
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Dosage & Formulator Specification
Estimated effective range from animal-to-human dose extrapolation: 50–200 mg/day of nobiletin equivalent. In PMF-standardised extract form, 150–300 mg/day of a 20–30% PMF extract provides this range. Some human studies have used 500–1000 mg/day of citrus peel extract standardised to total PMFs.
For metabolic formulations, recommend a PMF extract standardised to ≥20% nobiletin by HPLC. For cognitive support, ensure lipid-based delivery to optimise CNS penetration. Nobiletin logP ~4.4 supports soft gel or phytosome delivery over aqueous formats.
Nobiletin is light-sensitive; amber packaging or opaque encapsulation is recommended. It is thermostable and compatible with hot-fill processes. Combination with phosphatidylcholine (lecithin) at 1:2 ratio (nobiletin:lecithin) is documented to improve oral bioavailability 2–3-fold in animal studies.
Frequently Asked Questions — Nobiletin
Why is nobiletin considered a superior PMF to tangeretin?
Nobiletin has six methoxy groups versus tangeretin’s five, yielding higher lipophilicity and broader documented bioactivity. It has stronger metabolic (AMPK) and cognitive evidence than tangeretin, though both are frequently co-formulated as complementary PMFs.
Is there a standardised nobiletin extract available as a named ingredient?
No widely marketed named ingredient exists for nobiletin comparable to quercetin or berberine. Formulators typically specify citrus peel extract standardised to nobiletin % by HPLC. Specialist isolates (≥95% nobiletin) are available for premium-tier applications.
Can nobiletin be combined with metformin for metabolic formulations?
Both nobiletin and metformin activate AMPK, suggesting potential synergy in metabolic support formulations. However, concomitant use with metformin in diabetic patients warrants advisory language. No clinical interaction data specific to this combination exists.
What is the difference between nobiletin in orange peel and dried mandarin peel?
Sweet orange (Citrus sinensis) peel contains moderate nobiletin; King mandarin (Citrus nobilis) and C. reticulata are richer sources. Dried mandarin peel (chen pi) typically contains 0.2–1.5% nobiletin; concentrated extracts are required for formulation-relevant doses.
Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.
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