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

doi:10.12122/j.issn.1673-4254.2025.02.11

Abstract

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.

Key words: quercetin, astrocyte, stress granules, oxidative stress, HIV-1 gp120

Pengwei HUANG, Jie CHEN, Jinhu ZOU, Xuefeng GAO, Hong CAO. Quercetin mitigates HIV-1 gp120-induced rat astrocyte neurotoxicity via promoting G3BP1 disassembly in stress granules[J]. Journal of Southern Medical University, 2025, 45(2): 304-312.

Figures/Tables 6

Fig.1 Effects of concentration gradient of quercetin (QC) alone (A) and in combination with HIV-1 gp120. (B) on viability of primary rat astrocytes. ***P<0.001 vs 0 μmol/L. **P<0.01, ***P<0.001 vs HIV-1 gp120+0 μmol/L QC.

Fig.2 QC reduces the ratio of stress granule (SG)‑positive cells in HIV-1 gp120-induced primary rat astrocytes. A: Immunofluorescence staining of primary rat astrocytes. B: Ratio of SG-positive cells. C: Immunofluorescence intensity of G3BP1. D, E: Results of Western blotting for detecting G3BP1 protein expression level (fold of control). *P<0.05, **P<0.01, ***P<0.001 vs HIV-1 gp120 group.

Fig.3 QC reduces oxidative stress and promotes expression of SG-depolymerizing proteins in primary rat astrocytes in vitro. A: Specific activity of SOD and CAT and contents of GSH, H2O2 and MDA in primary rat astrocytes in each group. B: ROS level and fluorescence intensity. C: Western blotting for detecting expressions levels of SG-depolymerizing proteins in primary rat astrocytes. *P<0.05, **P<0.01, ***P<0.001 vs HIV-1 gp120 group. &P<0.05, &&P<0.01.

Fig.4 Effects of QC on oxidative stress indexes and expressions of SG-depolymerizing proteins in brain tissues of Gp120 tgm mice. A: Serum levels of SOD and CAT activities and GSH, H2O2 and MDA contents in each group. B: Results of Western blotting for detecting the expression levels of SG-depolymerizing proteins in the brain tissues of the mice in each group. *P<0.05, **P<0.01, ***P<0.001 vs Gp120 tgm group. &P<0.05.

Fig.5 QC decreases the level of SGs in the brain tissues of Gp120 tgm mice. A, B: Immunohistochemical staining for G3BP1 in the hippocampus and cortex. C, D: Results of Western blotting for detecting the expression level of G3BP1. **P<0.01, ***P<0.001 vs Gp120 tgm group.

Fig.6 QC improves cognitive function of Gp120 tgm mice. A-E: Results of Morris water maze test (A-C) and open field test (D-I) in each group. *P<0.05, **P<0.01, ***P<0.001 vs Gp120 tgm group.

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