Zhu Wenqian, Li Bingjin, Cui Ranji
Jilin Provincial Key Laboratory of Molecular and Chemical Genetic, Second Hospital of Jilin University, Changchun, Jilin Province, China.
Neural Regen Res. 2025 Apr 29. doi: 10.4103/NRR.NRR-D-24-00714.
Preliminary studies on emerging herbal ingredients have highlighted alternative pathways that inflammation and modulate perturbed immunity as valuable strategies for treating depression. Previous studies have shown that 5-O-methylvisammioside, a bioactive compound derived from Saposhnikoviae Radix, possesses excellent anti-inflammatory and antioxidant biological functions, exhibits a neuroprotective effect. The purpose of this study was to explore the targets and signaling pathways of 5-O-methylvisammioside in the potential treatment of major depressive disorder using a combination of network pharmacology analysis and biological experiments. The network pharmacological analysis results indicated that the proto-oncogene tyrosine-protein kinase Src and the nuclear factor kappa B signaling pathway were highly correlated with the treatment of major depressive disorder with 5-O-methylvisammioside. Further experiments indicated that 5-O-methylvisammioside significantly improved lipopolysaccharide-induced depression-like behaviors in mice, ameliorated microglial polarization in the hippocampal CA1 and CA3 regions, and inhibited Src phosphorylation and nuclear factor kappa B pathway activation. The effects of 5-O-methylvisammioside were similar to those of the Src inhibitor PP2. When 5-O-methylvisammioside was administered with PP2, no effects were observed on lipopolysaccharide-induced depression-like behaviors in mice, nuclear factor kappa B pathway proteins, and microglial polarization. These findings indicate that 5-O-methylvisammioside may exert its antidepressant potential by inhibiting Src-mediated activation of the nuclear factor kappa B signaling pathway. Therefore, 5-O-methylvisammioside might serve as a promising Chinese herbal medicine for the prevention and treatment of depression.
对新兴草药成分的初步研究突出了炎症和调节紊乱免疫的替代途径，作为治疗抑郁症的有价值策略。先前的研究表明，5-O-甲基维斯阿米醇苷，一种从防风中提取的生物活性化合物，具有出色的抗炎和抗氧化生物学功能，表现出神经保护作用。本研究的目的是结合网络药理学分析和生物学实验，探索5-O-甲基维斯阿米醇苷在重度抑郁症潜在治疗中的靶点和信号通路。网络药理学分析结果表明，原癌基因酪氨酸蛋白激酶Src和核因子κB信号通路与5-O-甲基维斯阿米醇苷治疗重度抑郁症高度相关。进一步实验表明，5-O-甲基维斯阿米醇苷显著改善了脂多糖诱导的小鼠抑郁样行为，改善了海马CA1和CA3区域的小胶质细胞极化，并抑制了Src磷酸化和核因子κB通路激活。5-O-甲基维斯阿米醇苷的作用与Src抑制剂PP2相似。当5-O-甲基维斯阿米醇苷与PP2联合给药时，对脂多糖诱导的小鼠抑郁样行为、核因子κB通路蛋白和小胶质细胞极化未观察到影响。这些发现表明，5-O-甲基维斯阿米醇苷可能通过抑制Src介导的核因子κB信号通路激活发挥其抗抑郁潜力。因此，5-O-甲基维斯阿米醇苷可能是一种有前途的预防和治疗抑郁症的中药。
