ArticleAIDS research and therapy2026
Quercetin ameliorates HIV-1 gp120 protein-induced intestinal barrier dysfunction by inhibiting the activation of the ERK1/2 signaling pathway in a Caco-2 cell model.
Article in AIDS research and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Vitamin D and Intestinal Diseases: Impact on Intestinal Immunity and Gut Barrier Function.Diseases (Basel, Switzerland) · 2026Review
- Mechanisms by which tryptophan metabolites enhance intestinal barrier function to prevent necrotizing enterocolitis in preterm infants.Frontiers in immunology · 2026Review
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Authors and funding
7 authors.
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Abstract
backgroundPeople living with HIV (PLWH) frequently experience non-AIDS comorbidities, driven in part by persistent intestinal barrier dysfunction and systemic inflammation. The HIV-1 envelope protein gp120 has been implicated in damaging epithelial tight junctions. However, therapeutic options for preserving intestinal integrity are limited.
methodsA Caco-2 cell monolayer model was used to simulate HIV-1 gp120-induced intestinal barrier injury. Barrier integrity, tight junction protein expression, apoptosis, and MAPK/ERK1/2 pathway activity were evaluated in the presence or absence of Quercetin. Transcriptomic analysis and Western blotting were performed to investigate mechanisms, including the role of dual-specificity phosphatases (DUSPs) and myosin light chain kinase (MLCK).
resultsGp120 exposure increased epithelial permeability, decreased tight junction protein expression (ZO-1, Occludin, Claudin-1), and induced apoptosis. Quercetin treatment significantly restored barrier integrity, reduced apoptosis, and enhanced tight junction expression. Mechanistically, Quercetin suppressed ERK1/2 phosphorylation, upregulated DUSP4, DUSP5, and DUSP8, and inhibited downstream MLCK/MLC activation. The MEK inhibitor U0126 produced similar protective effects, confirming ERK1/2 involvement.
conclusionsQuercetin alleviates gp120-induced intestinal barrier disruption via inhibition of the ERK1/2-MLCK signaling pathway and restoration of tight junction proteins. These findings highlight the therapeutic potential of Quercetin as a natural compound to protect against HIV-related mucosal injury and support its further development for managing HIV-associated comorbidities.
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