Neuroprotective Effects of Ginsenoside Rg3 in Depressed Mice via Inhibition of the C1q Complement Pathway

TL;DR

Ginsenoside Rg3 protects neurons in depressed mice by inhibiting the C1q complement pathway and reducing microglial activation.

Contribution

This study identifies Ginsenoside Rg3 as a potential treatment for depression by targeting the C1q complement pathway and microglial activation.

Findings

Depressed mice showed increased C1q levels and activated microglia with reduced synapses.

Ginsenoside Rg3 reduced C1q levels, inhibited microglial activation, and improved depression-like behaviors.

In vitro, Rg3 protected neurons by reducing complement factor secretion and inhibiting apoptosis.

Abstract

To explore the neuroprotective effect of Ginsenoside Rg3 in a mouse model of depression induced by chronic restraint, and to elaborate whether it exerts a protective effect by inhibiting the upregulation of complement factor C1q and related microglial cell‐mediated synaptic injury.

The mouse chronic restraint model of depression was prepared from male C57BL/6 mice. The depression‐like behaviors of mice were detected by sugar water preference, forced swimming test and tail suspension test. The neuronal phenotypes of mice were detected by Nissl staining, HE and Golgi staining. The expression of complement‐related pathway proteins was detected by Western Blot. The corticosterone content in the peripheral blood of mice in each group was detected by corticosterone kit. Molecular simulation and MST were used to detect the binding of Rg3 and C1q. Establish a co‐culture model of microglia and neurons; corticosterone stimulation and Rg3 pre‐protection were given to detect the damaging effect of microglial activation on neurons and the protective effect of Rg3.

In vivo experiments show that as depression progresses, the levels of complement factor C1q significantly increase, which is similar to the manifestations observed in depressed patients. Moreover, microglial cells in the hippocampus of depressed mice are significantly activated, while the number of neuronal synapses is significantly reduced, displaying apoptotic features. Ginsenoside Rg3, a drug with neuroprotective effects, reduces complement C1q levels and inhibits microglial activation, thereby protecting neurons and improving depression‐like behaviors. In vitro experiments show that CORT can induce microglial cells to secrete complement factor C1q, which may trigger neuronal apoptosis. Ginsenoside Rg3 may protect HT22 neurons by regulating microglial activation, reducing the secretion of complement factors, and inhibiting neuronal apoptosis.

These results suggest that inhibiting excessive microglial activation and complement factor levels could be a potential strategy for treating depression.

Complement factors mediate microglial activation and their phagocytic function in a chronic inflammatory environment. Ginsenoside Rg3 may reduce complement factor secretion and inhibit neuronal apoptosis by regulating microglial activation, thereby exerting a protective effect on neurons.

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