Ginsenoside Rb1 prevents lipopolysaccharide-induced depressive-like behavior by inhibiting inflammation and neural dysfunction and F2 elicits a novel antidepressant-like effect: A metabolite-based network pharmacology study

抗抑郁药 药理学 炎症 神经炎症 医学 代谢物 行为绝望测验 人参 内科学 海马体 病理 替代医学
作者
Wenyi Liang,Бо Лю,Kun Zhou,Ping Jian,Qiunan Zhang,Zihao Chang,Lingfang Wu,Chang Hong-sheng,Lanzhen Zhang
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:282: 114655-114655 被引量:15
标识
DOI:10.1016/j.jep.2021.114655
摘要

Inflammatory responses are associated wieh the pathophysiology of depression. Ginsenoside Rb1 (Rb1) exerts antidepressant effect, but the relationship between its activity and inflammation remains unclear.In this study, the antidepressant-like effect and underlying mechanisms of Rb1 were been investigated.The neuroinflammatory mouse model of lipopolysaccharide (LPS)-induced acute depression-like behavior was employed to detect the action of Rb1. An integrative strategy combining the identification of prototype (Rb1) and its metabolites in vivo with network pharmacology analysis was used to explore therapeutic mechanisms of these ingredients. The putative targets and signalings were experimentally validated. The antidepressant-like effect of F2, the metabolite of Rb1, was firstly evaluated.Rb1 significantly ameliorated LPS-induced depressive-like behavior. Rb1 and its metabolites (Rd, F2, compound K, Rh2, Rg3, PPD) were identified and then a disease-component-target network was established. Experimental validation showed that Rb1 inhibited peripheral and hippocampal inflammation via MAPK/NF-κB signaling. In inflammatory-mediated depression state, Rb1 improved impaired glucocorticoid receptor, suppressed indoleamine 2,3-dioxygenase activity, increased 5-HT level and 5-HT1A receptor expression. Additionally, F2 was firstly discovered to exert antidepressant-like effect, and it existed higher activity than Rb1 against depression.The study highlighted the potential of Rb1 and F2 as healthy supplement or agent for inflammation-induced depression.
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