Work

Verbascoside inhibits OGD/R-induced SK-N-SH cell injury by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway

Year: 2025

Type: article

Abstract: The potential therapeutic value of verbascoside (VB) has been reported in a variety of diseases, including cerebral hemorrhage. In this study, we aimed to explore the underlying mechanism of VB in cerebral ischemic stroke. The in vitro ischemic stroke model was established by Oxygen-glucose deprivation/reoxygenation (OGD/R) model. CCK-8 assay and EdU assay were performed for cell proliferation. Flow cytometry analysis was adopted to analyze cell apoptosis. ELISA kits were used to estimate the concentrations of inflammatory factors. Ferroptosis-related markers were examined with indicated commercial kits. The relations of METTL14, CHAC1 and IGF2BP2 were analyzed by MeRIP assay, RIP assay and Actinomycin D assay. Gene expression was determined by qRT-PCR and western blot. VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells. VB decreased METTL14 expression in OGD/R-treated SK-N-SH cells and METTL14 knockdown alleviated OGD/R-induced injury of SK-N-SH cells. METTL14 and IGF2BP2 mediates m6A modification of CHAC1. CHAC1 overexpression abrogated the effects of METTL14 knockdown on OGD/R-induced SK-N-SH cell injury. Moreover, the effects of VB on OGD/R-treated SK-N-SH cell proliferation, apoptosis, inflammation and ferroptosis were abated by elevating METTL14 or CHAC1. Besides, VB reduced the levels of NRF2, SLC7A11 and GPX4 in OGD/R-treated SK-N-SH cells, while METTL14 or CHAC1 overexpression reversed the effects. VB promoted the proliferation and inhibited apoptosis, inflammation and ferroptosis in OGD/R-treated SK-N-SH cells by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway. • VB reduces METTL14 expression in OGD/R-treated SK-N-SH cells. • METTL14 knockdown abrogates OGD/R-induced injury of SK-N-SH cells. • METTL14 and IGF2BP2 mediates m6A modification of of CHAC1. • METTL14 knockdown abrogates OGD/R-induced injury of SK-N-SH cells by regulating CHAC1. • VB inhibits OGD/R-induced SK-N-SH cell injury by regulating METTL14/CHAC1/NRF2/SLC7A11/GPX4 pathway.

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111543

Authors: Liwei Wen, Cheng Zhang, Xia Zhou, Jiaxing Feng, Qiang Li, Fubing Yang

Institutions: Southwest Medical University, Affiliated Hospital of Southwest Medical University

Language: English

Topic: Neurological Disorders and Treatments

Subfield: Neurology

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280