Quercetin mitigates HIV-1 gp120-induced rat astrocyte neurotoxicity via promoting G3BP1 disassembly in stress granules

HUANG Pengwei; CHEN Jie; ZOU Jinhu; GAO Xuefeng; CAO Hong

doi:10.12122/j.issn.1673-4254.2025.02.11

Abstract：Objective To explore the effect of quercetin for mitigating HIV-1 gp120-induced astrocyte neurotoxicity and its underlying mechanism.Methods Primary rat astrocytes were isolated and treated with quercetin,HIV-1 gp120,or gradient concentrations of quercetin combined with HIV-1 gp120.The formation of stress granules(SGs)in the treated cells was observed with immunofluorescence assay,and the levels of oxidative stress markers and protein expressions were measured using specific assay kits and Western blotting.HIV-1 gp120 transgenic mice were treated with quercetin(50 mg/kg)by gavage for 4 weeks,and the changes in cognitive functions and oxidative stress levels were examined by behavioral assessments,oxidative stress index analysis in serum,and immunohistochemical and Western blotting of the brain tissue.Results In primary rat astrocytes,treatment with quercetin significantly reduced HIV-1 gp120-induced SG formation,increased the levels of antioxidant indexes,decreased the levels of oxidative substances,and up-regulated protein level associated with SG depolymerization.In the transgenic mouse models,quercetin obviously improved the cognitive function of the rats,reduced oxidative stress levels,and promoted the expression of proteins associate with SG depolymerization in the brain tissues.Conclusion Quercetin mitigates HIV-1 gp120-induced astrocyte neurotoxicity and cognitive function impairment by inhibiting oxidative stress,enhancing expressions of SG depolymerization-related proteins,and promoting SG disassembly,suggesting the value of quercetin as a potential therapeutic agent for neuroprotection in HIV-associated neurocognitive disorders.