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

Authors

Lingling Tian, SiJie Zhang, Ziyang Ye, Jianbo Qing, Feng Wu, Qian Wang, Rongshan Li, Yafeng Li, Qi Duan

Published in

Renal failure. Volume 48. Issue 1. Pages 2677257. Epub Jun 29, 2026.

Abstract

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a leading cause of end-stage renal disease, but effective therapies remain scarce. This study investigated the renoprotective effects and mechanisms of inotodiol (INO), a lanostane triterpenoid from Inonotus obliquus, using db/db mice (in vivo) and high glucose-treated MPC5 podocytes (in vitro). Renal histopathology, function, and oxidative stress markers were assessed in vivo; reactive oxygen species, cytotoxicity, and apoptosis were measured in vitro. Protein expression levels of apoptosis-related factors, podocyte injury markers, oxidative stress indicators, and PI3K/Akt/GSK-3β pathway components were analyzed. INO treatment significantly reduced fasting blood glucose, blood urea nitrogen, serum creatinine, and urinary albumin-to-creatinine ratio in db/db mice while restoring podocyte markers (synaptopodin, WT-1). It ameliorated renal histopathology and oxidative stress, as evidenced by decreased KEAP1, NOX4, and malondialdehyde, along with increased superoxide dismutase, catalase, glutathione peroxidase, Nrf2, NQO1, and heme oxygenase-1. INO also suppressed apoptosis, reducing cytochrome c, Bax, and cleaved caspase-3 while elevating Bcl-2. Mechanistically, INO activated the PI3K/Akt pathway, which in turn inhibited GSK-3β activity, thereby attenuating oxidative stress, apoptosis, and podocyte injury both in vivo and in vitro. Taken together, INO protects against DN by mitigating oxidative stress and apoptosis via the PI3K/Akt/GSK-3β signaling pathway, highlighting its potential as a promising therapeutic candidate for DN.

PMID:
42367005
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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