Melatonin facilitates the anti-EV71 activity by inhibiting apoptosis through the regulation of the Caspase-7 signaling pathway
Year: 2025
Type: article
Abstract: To investigate the impacts and potential underlying mechanisms of melatonin on enterovirus 71(EV71). Three-day-old ICR mice were randomly divided into seven groups: control group, vehicle group, melatonin 10, 50, and 100 mg/kg group, ribavirin 50 mg/kg group, and melatonin 50 mg/kg combined ribavirin 50 mg/kg group. The mice were intracranial injected with 50 μL EV71 (5 ×10 3 TCID 50 ) and treated with different medications once a day for four days. Clinical scores, body weights of mice were recorded, and the expression of VP1 protein in the hindlimb muscles and brainstem was analyzed using western blot. In vitro, CCK-8 assays were employed to assess cell proliferation, Reed-Muench method was used to calculate viral titers, western blot was conducted to evaluate the expression of VP1 and caspase-7 proteins, flow cytometry and TMRE staining were utilized to assess cell apoptosis, molecular docking was performed to calculate binding activity. Melatonin significantly alleviated the clinical symptoms induced by EV71 and effectively suppressed the expression of VP1 protein in the hindlimb muscles and brainstem of mice. In vitro, Melatonin effectively reduced the TCID 50 and the expression of VP1 protein and rescued the apoptosis induced by EV71; Melatonin enhanced the fluorescence intensity of TMRE compared to the infected group; the binding energy between melatonin and caspase-7 was calculated to be −7.2 kcal/mol, and melatonin inhibited the expression of caspase-7 protein after EV71 infection. Melatonin inhibited EV71 replication both in vivo and vitro, and its mechanism may involve preventing EV71-induced apoptosis by inhibiting the expression of cleaved caspase-7. • Melatonin suppresses EV71 replication in mice and cell models. • Melatonin inhibits EV71-induced apoptosis via Caspase-7 blockade. • Melatonin-ribavirin combination enhances anti-EV71 efficacy.
Source: Biomedicine & Pharmacotherapy
Authors: Zhengyun Liu, Jiarong Xie, Mingxia Xiong, Haiyan Yang, Huan Wang
Institution: Zunyi Medical University
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,610
OpenAlex ID: W4412483465