Salidroside Mitigates Cerebral Ischemic Injury via Modulation of the PVT1/miR-384-5p Regulatory Axis.

Cerebrovascular accidents, particularly ischemic stroke, constitute a paramount global health burden. While Salidroside (Sal), extracted from Rhodiola rosea, shows promise for neuroprotection, the specific molecular pathways mediating these effects, particularly the role of long non-coding RNA PVT1 and its interaction with miR-384-5p, remain unexplored. This investigation sought to fill this gap by deciphering how Sal influences cerebral ischemic pathology through the PVT1/miR-384-5p regulatory axis. Using murine middle cerebral artery occlusion (MCAO) and microglial BV2 cell oxygen-glucose deprivation (OGD) models, we evaluated neurological function, tissue damage, cellular viability, and molecular markers. We examined interactions between long non-coding RNA PVT1 and miR-384-5p through molecular techniques including dual-luciferase assays and RNA immunoprecipitation, while assessing oxidative parameters and inflammatory mediators. Sal administration (100 mg/kg/day) markedly improved neurological outcomes (35% reduction in deficit scores, p < 0.01) and diminished infarct dimensions by 42% in MCAO mice. Histological examination revealed preservation of neural architecture with 65% reduction in neuronal damage rate and 58% decrease in TUNEL-positive apoptotic cells in treated animals. At the cellular level, Sal preserved microglial viability (68% survival vs. 41% in OGD alone) while reducing reactive oxygen species generation by 52% and pro-inflammatory cytokine production (TNF-α by 61%, IL-1β by 55%, IL-6 by 48%). Importantly, cerebral ischemia elevated PVT1 expression 3.2-fold, which Sal effectively counteracted. Rescue experiments demonstrated that PVT1 overexpression abolished the protective benefits conferred by Sal treatment, confirming the functional significance of the PVT1/miR-384-5p regulatory circuit. Sal mitigates cerebral ischemic injury through disruption of the PVT1/miR-384-5p regulatory circuit, providing both mechanistic insights and a potential therapeutic strategy for ischemic stroke intervention. These findings establish specific molecular targets for pharmacological development in stroke therapy.