Asiatic acid prevents glucocorticoid-induced femoral head osteonecrosis via PI3K/AKT pathway

Area of Science:

• Orthopedics
• Pharmacology
• Cell Biology

Background:

• Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a major cause of non-traumatic osteonecrosis, leading to significant pain and reduced mobility.
• Centella asiatica (CA) and its primary constituent, asiatic acid (AA), possess anti-inflammatory, anti-apoptotic, and antioxidant properties with potential therapeutic applications in orthopedic conditions.

Purpose of the Study:

• To investigate the potential of asiatic acid (AA) in alleviating GIONFH by suppressing oxidative stress and apoptosis.
• To elucidate the cellular and molecular mechanisms underlying AA's therapeutic effects in GIONFH.

Main Methods:

• Network pharmacology analysis was employed to identify the correlation between AA and GIONFH target genes.
• In vitro studies utilized dexamethasone (DEX)-induced apoptosis in rat osteoblasts.
• In vivo studies used a rat model of GIONFH to verify the therapeutic efficacy and mechanisms of AA.

Main Results:

• Network pharmacology revealed multiple target genes linking AA and GIONFH.
• AA inhibited DEX-induced osteoblast apoptosis by modulating BAX, BCL-2, Cleaved-caspase3, and cleaved-caspase9.
• AA reduced reactive oxygen species (ROS) and oxidative stress via the mitochondrial pathway, activating the PI3K/AKT signaling pathway.
• AA treatment ameliorated GIONFH progression in a rat model.

Conclusions:

• Asiatic acid (AA) effectively mitigates glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) by inhibiting osteoblast apoptosis and oxidative stress.
• The therapeutic mechanism of AA in GIONFH involves the activation of the PI3K/AKT pathway.
• AA demonstrates significant potential for preventing and treating GIONFH.