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Nobiletin is a polymethoxylated flavonoid naturally found in the peel of citrus fruits, notably tangerines and sweet oranges. Structurally, it is a hexamethoxyflavone (C21H22O8). Nobiletin exhibits a broad range of biological activities in vitro and in vivo, including antioxidant, anti-inflammatory, antitumor, antidiabetic, neuroprotective, and cardioprotective effects. Its main mechanisms of action involve modulation of multiple molecular signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor alpha (PPAR-α), extracellular signal-regulated kinase (ERK), protein kinase B (AKT), toll-like receptor 4 (TLR4), and transcription factor EB (TFEB)[1][3][4][9][7]. Preclinical studies suggest roles in improving liver function, insulin resistance, glucose uptake, reducing inflammation and oxidative stress, remodeling gut microflora, and supporting neuronal survival. Nobiletin is being investigated mainly as a dietary supplement ingredient, although combination clinical studies (e.g., with tangeretin) have been conducted for conditions such as nocturia[6]. High-quality clinical trial evidence is lacking for any therapeutic indication[4].
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