Unveiling the Health Potential of Myricetin: Bio-accessibility, Safety Considerations, and Therapeutic Mechanisms.

Myricetin, a naturally occurring flavanol, has gained significant attention due to its diverse pharmacological properties, including antioxidant, anti-inflammatory, anticancer, antidiabetic, and neuroprotective effects. Found abundantly in various plant families, such as Myricaceae, Anacardiaceae, and Polygonaceae, Myricetin exerts its therapeutic effects by modulating key cellular pathways, including Nrf2/HO-1, MAPK, and PI3K/Akt signaling. This review systematically evaluates Myricetin's bioaccessibility, pharmacokinetics, and therapeutic potential, highlighting its role in modulating oxidative stress, inhibiting tumor proliferation, and protecting against neurodegenerative diseases. Despite its promising benefits, Myricetin exhibits limited bioavailability due to poor aqueous solubility and extensive phase II metabolism (glucuronidation and sulfation). Additionally, Myricetin interacts with cytochrome P450 enzymes (CYP3A4, CYP2C9, CYP2D6), potentially altering drug metabolism and increasing the risk of drug interactions. Toxicological studies indicate an LD50 of 800 mg/kg in mice, with potential hepatic and renal toxicity at high doses, mainly due to redox cycling and quinone formation. While Myricetin shows excellent radical-scavenging properties, it may act as a pro-oxidant in the presence of metal ions, leading to oxidative stress and cellular damage. This review underscores the need for advanced formulation strategies to enhance bioavailability and mitigate toxicity risks. Future clinical investigations are essential to establish optimal therapeutic dosages, assess long-term safety, and validate Myricetin's potential as a nutraceutical and therapeutic agent in chronic diseases.