Preclinical evidence of chrysin in metabolic disorder via mitochondrial signaling: a mechanistic review.

Metabolic disorders involve impaired glucose and lipid homeostasis, insulin resistance, chronic low-grade inflammation, and mitochondrial dysfunction, all of which contribute to the development of type 2 diabetes mellitus and related cardiometabolic complications. Recent evidence emphasises mitochondrial signaling as a key regulator of cellular energy balance and metabolic flexibility, positioning it as a promising therapeutic target. Chrysin, a naturally occurring flavone found abundantly in honey, propolis, and various medicinal plants, has attracted interest for its metabolic regulatory properties in preclinical studies. This mechanistic review critically examines experimental evidence on how chrysin influences metabolic disorders through mitochondrial signaling pathways. Preclinical studies demonstrate that chrysin improves mitochondrial bioenergetics by enhancing oxidative phosphorylation efficiency, ATP generation, and mitochondrial biogenesis, while simultaneously reducing excessive reactive oxygen species production. Chrysin has been shown to activate key energy-sensing pathways, including AMP-activated protein kinase and downstream regulators, thereby promoting glucose uptake, suppressing hepatic gluconeogenesis, and improving insulin sensitivity in peripheral tissues. Additionally, chrysin-mediated modulation of mitochondrial dynamics and antioxidant defence systems contributes to the attenuation of inflammation and lipid accumulation. In adipose and hepatic tissues, these effects translate into improved lipid metabolism, reduced free fatty acid release, and normalisation of metabolic enzyme expression. Collectively, the available preclinical evidence supports chrysin as a multi-target metabolic modulator acting through mitochondrial signaling networks.