[The Chinese medicine Gandouling attenuates brain injury in hepatolenticular degeneration mice by inhibiting ferroptosis via the SIRT1/FoxO3 pathway].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2026

Wu K, Wang N, Zhao D, Wei W, Zhang W et al.

Abstract

OBJECTIVES: To investigate the mechanism by which the Chinese medicine Gandouling protects against brain injury in hepatolenticular degeneration (Wilson’s disease) through regulation of the SIRT1/FoxO3 pathway-mediated ferroptosis. METHODS: TX mice were randomly divided into six groups: model control, Gandouling, resveratrol (SIRT1 activator), Gandouling+resveratrol, EX-527 (SIRT1 inhibitor), and Gandouling+EX-527 groups, with DL mice serving as the blank control group. After a 4-week intervention, neurological function was assessed using the Morris water maze test, wire hanging test, and pole test. Apoptosis in basal ganglia tissue was detected by TUNEL assay. Reactive oxygen species (ROS) levels in basal ganglia tissue were measured using the DCFH-DA method, while ferrous iron (Fe²⁺) and malondialdehyde (MDA) levels were determined by colorimetric assays. Immunofluorescence was used to evaluate the fluorescence intensity of SIRT1 and FoxO3. The protein expression levels of SIRT1, FoxO3, GPX4, SLC7A11, ACSL4, FTH1, and P53 were assessed by Western blotting, and the mRNA expression levels of RESULTS: Compared with the blank control group, the model control group exhibited significant neurological impairment (prolonged escape latency, reduced platform crossing frequency, and prolonged pole-climbing time), increased neuronal apoptosis, decreased transcription and expression of CONCLUSIONS: Gandouling inhibits neuronal ferroptosis by regulating the SIRT1/FoxO3 signaling pathway, thereby improving neurological function in model mice.

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