Wuling powder alleviates depressive-like behavior by attenuating endoplasmic reticulum stress in the mouse hippocampus

doi:10.5246/jcps.2024.09.058

Abstract

Abstract:

The response to endoplasmic reticulum (ER) stress has been noted in both human depression cases and depression models in rodents. Wuling powder, derived from the mycelium of the esteemed fungus Xylaria Nigripes (Kl.) Sacc, has demonstrated efficacy in alleviating depressive symptoms. The purpose of this research was to explore the antidepressant properties of Wuling powder and its basic molecular effects, particularly regarding alterations in ER stress. A model of social defeat stress was created by introducing a mouse to the cage of an unfamiliar, hostile mouse for intervals of 5–10 min daily over a span of 10 d. Subsequently, the mice received oral doses of Wuling powder for 2 weeks. The social approach-avoidance assay was employed to evaluate signs of depression-like behaviors. Moreover, protein and gene expressions linked to ER stress triggered by social defeat were analyzed through Western blotting analysis and quantitative real-time PCR. The behavioral tests indicated that Wuling powder ameliorated behaviors associated with depression due to social defeat stress. Treatment with Wuling powder markedly reduced the increased levels of the 78-kDa glucose-regulated protein and protein disulfide isomerase caused by social defeat stress. It also diminished the expression of inositol-requiring enzyme 1α (IRE1α) and spliced X box-binding protein-1 (sXBP1) at the protein and mRNA levels. Furthermore, Wuling treatment notably decreased the levels of phosphorylated eukaryotic initiation factor 2 alpha kinase (P-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), simultaneously enhancing the ratio of B-cell lymphoma 2 (Bcl-2) to Bcl-2-associated X protein (Bax). These results suggested that Wuling powder could alleviate ER stress and inhibit cell apoptosis in the hippocampus by inhibiting protein translation and synthesis, thereby attenuating depressive-like behavior.

Key words: Depression, Wuling powder, Endoplasmic reticulum stress, Unfolded protein response

Supporting:

Lu Feng, Wei Huang, Ji Zheng, Dongmei Li, Mingyang Wang, Junya Liu, Shujie Fan, Chao Ji, Nan Yang, Yanyong Liu. Wuling powder alleviates depressive-like behavior by attenuating endoplasmic reticulum stress in the mouse hippocampus[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(9): 783-794.

Figures/Tables 6

References 29

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