Inotodiol ameliorates oxidative stress and apoptosis by regulating PI3K/Akt/GSK-3β signaling pathways in diabetic...

Area of Science:

• Pharmacology
• Nephrology
• Biochemistry

Background:

• Diabetic nephropathy (DN) is a severe complication of diabetes, leading to end-stage renal disease with limited therapeutic options.
• Oxidative stress and apoptosis are key contributors to DN pathogenesis.

Purpose of the Study:

• To investigate the renoprotective effects and underlying mechanisms of inotodiol (INO), a compound from Inonotus obliquus, against diabetic nephropathy.
• To evaluate INO's impact on oxidative stress, apoptosis, and podocyte injury in both animal models and cell cultures.

Main Methods:

• In vivo studies utilized db/db mice to assess renal function, histopathology, and oxidative stress markers.
• In vitro studies employed high glucose-treated MPC5 podocytes to measure reactive oxygen species, cytotoxicity, and apoptosis.
• Protein expression analysis focused on apoptosis factors, podocyte injury markers, oxidative stress indicators, and the PI3K/Akt/GSK-3β pathway.

Main Results:

• INO treatment significantly improved renal function and reduced albuminuria in db/db mice.
• INO ameliorated renal histopathology and oxidative stress by modulating key markers (e.g., decreasing NOX4, increasing Nrf2).
• INO suppressed apoptosis and podocyte injury by activating the PI3K/Akt/GSK-3β pathway, reducing pro-apoptotic factors and increasing anti-apoptotic Bcl-2.

Conclusions:

• Inotodiol demonstrates significant renoprotective effects against diabetic nephropathy in preclinical models.
• INO mitigates DN by reducing oxidative stress and apoptosis via the PI3K/Akt/GSK-3β signaling pathway.
• INO holds potential as a novel therapeutic agent for managing diabetic nephropathy.