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5-O-Methylvisammioside alleviates depression-like behaviors by inhibiting nuclear factor kappa B pathway activation via targeting SRC

Year: 2025

Type: article

Abstract: 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.

Source: Neural Regeneration Research

DOI: 10.4103/nrr.nrr-d-24-00714

Authors: Wenqian Zhu, Bingjin Li, Ranji Cui

Institutions: Jilin University, Second Affiliated Hospital of Jilin University

Language: English

Topic: Medicinal Plant Extracts Effects

Subfield: Complementary and alternative medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500