Antidepressant Effect Of Ginsenoside Rg1-dependent NLRP3 Inflammasome

When patients suffering from mood disorders pursue medical attention,a large percentage of them have only a very limited response to available medications.Only onethird of patients with depression are currently able to achieve sustained antidepressant effects.The need for rapid initiation,maintenance and relapse prevention of antidepressant drugs is growing,and there is an urgent need for the development and investigation of new antidepressant drugs.The onset of depression is associated with many factors,including the environment.Therefore,we need to better understand the mechanisms of depression to identify more effective treatment targets.Numerous studies have shown that depression is often accompanied by two processes within the center of patients with depression: the activation of microglia and the neuroinflammatory response.They are two key factors in the pathogenesis of depression.IL-1β is a major inducer of neuroinflammation and it is overexpressed in the brains of depressed patients.The secretion of IL-1β in the central nervous system(CNS)is tightly controlled by NLRP3 inflammasome.Within the CNS,NLRP3 inflammasome are highly expressed in microglia,and NLRP3 inflammasome are intracellular protein complexes that induce maturation of caspase-1,which processes pro-IL-1β into a mature molecule ultimately leading to neuroinflammation.Ginseng is one of the most commonly used herbal medicines in the world,and ginsenosides are the main bioactive components of ginseng,have a wide range of pharmacological effects.The anti-inflammatory,anti-apoptotic and neuroprotective properties of ginsenoside Rg1 have been previously investigated.However,how the neuroprotective mechanisms exerted by Rg1 remain largely inexact.In this study,we used a chronic mild stress(CMS)model to explore the activation of a central critical cell,microglia,and the mechanisms of microglia involvement in neuroinflammation.The results show that GRg1 significantly ameliorates depression-like behavior after CMS treatment and helps mice return to a normal physiological state.And GRg1 treatment exerts its pharmacological effects by reducing neuroinflammation and microglial activation.Further studies revealed that the activation of NLRP3 inflammasome leads to the release of mature IL-1β,a process involved in the development of central neuroinflammation,and that the treatment effect of GRg1 is to inhibit the activation of NLRP3 inflammasome by blocking the formation and oligomerization of ASC speck in microglia,which ultimately results in the mitigation of neuroinflammation.This study investigated the neuroprotective effect of GRg1 on antidepressant mechanism,demonstrated the comprehensive and effective therapeutic potential of traditional Chinese medicine,and expected to provide a theoretical basis for the development of novel clinical antidepressants.