Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function

Kaempferol, a natural flavonoid present in fruits, vegetables, and teas, provides beneficial effects for human health. In this study, we investigated the protective effects of kaempferol on antimycin A (AMA)-induced toxicity in osteoblast-like MC3T3-E1 cells. Exposure of MC3T3-E1 cells to AMA caused significant cell viability loss, as well as mitochondrial membrane potential dissipation, complex IV inactivation, intracellular calcium ([Ca²⁺](i)) elevation, and reactive oxygen species (ROS) production. Pretreatment with kaempferol prior to AMA exposure significantly reduced AMA-induced cell damage by preventing mitochondrial membrane potential dissipation, complex IV inactivation, [Ca²⁺](i) elevation, and ROS production. Kaempferol also induced the activation of PI3K (phosphoinositide 3-kinase), Akt (protein kinase B), and CREB (cAMP-response element-binding protein) inhibited by AMA, which result demonstrates that kaempferol utilizes the PI3K/Akt/CREB pathway to augment metabolic activity inhibited by AMA. All these data indicate that kaempferol may reduce or prevent osteoblasts degeneration in osteoporosis or other degenerative disorders.