Isovitexin restores sevoflurane‑induced cognitive dysfunction by mediating autophagy through activation of the PGC‑1α/FNDC5 signaling pathway
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Updated: Aug 26, 2025

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Published on: June 6, 2025
Yuanyuan Guo1, Qibin Chen2, Bin Wu2
1Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; guo_yy12@163.com.
Abstract:
Postoperative cognitive dysfunction is a severe neurological complication. How to improve the cognitive impairment caused by sevoflurane, a most common inhaled anesthetic, remains a question worthy of studying. Isovitexin (IVX) is a trihydroxyl flavonoid that is a naturally bioactive ingredient found in various medicinal plants and has antioxidant, anti‑inflammatory and neuroprotective properties. The role of IVX in anesthetic‑induced nerve injury is rarely reported and the mechanisms are unclear. In this study, we found that IVX improved the cognitive dysfunction induced by sevoflurane in rats. It inhibited sevoflurane‑induced cell apoptosis. In addition, IVX increased sevoflurane‑induced autophagy in rat brain. Mechanically, IVX activated the PGC‑1α/FNDC5 pathway in rat brain, and depletion of FNDC5 could inhibit the neuroprotective function of IVX. In conclusion, our results suggested that IVX restored sevoflurane‑induced cognitive dysfunction by mediating autophagy through the activation of the PGC‑1α/FNDC5 pathway.
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