Puerarin 6″-O-xyloside improves postmenopausal lipid metabolic disorders via the PPARα-mediated FAO pathway

Pueraria lobata (Willd.) has long been used in traditional medicine to alleviate menopausal symptoms and is commonly employed in clinical settings. Puerarin 6″-O-xyloside (P6OX), a naturally occurring isoflavone isolated from this plant. It is structurally similar to known phytoestrogens and may modulate metabolic homeostasis. However, its effects on lipid metabolism disturbances in postmenopausal women and the underlying molecular mechanisms remain largely unexplored.

To evaluate the therapeutic effects of P6OX on postmenopausal lipid metabolic disorders and to elucidate the underlying molecular mechanisms.

To evaluate the efficacy of P6OX, an ovariectomized mouse model subjected to a high-fat diet (OVX + HFD) was established to mimic postmenopausal lipid metabolic disorders. In vitro studies were conducted using free fatty acid (FFA)-treated HepG2 cells. Potential molecular targets were identified through transcriptomic analysis. The involvement of the PPARα signaling pathway was further confirmed using the antagonist GW6471.

P6OX administration significantly reduced body weight, ameliorated obesity phenotypes, improved serum lipid profiles, decreased hepatic lipid accumulation and adipocyte size, and enhanced energy metabolism in OVX+HFD mice. These effects were associated with upregulated PPARα expression and induction of its FAO-linked downstream genes. In FFA-treated HepG2 cells, P6OX effectively attenuated intracellular lipid deposition and enhanced fatty acid oxidation. The observed effects of P6OX appeared to depend on PPARα signaling, underscoring its regulatory significance.

P6OX ameliorates postmenopausal lipid metabolic disorders by activating the PPARα-regulated FAO pathway, suggesting its promise as a natural, mechanism-based alternative for metabolic management.