Salidroside alleviates intestinal barrier injury in mice by activating PINK1/Parkin mediated mitophagy under chronic heat stress.

With global warming and the increasing frequency of extreme heat events, heat stress (HS) has emerged as a prevalent environmental stressor that severely threatens animal and human health, induces intestinal oxidative stress and damage, and subsequently induces systemic adverse reactions. Salidroside (SA), a natural antioxidant glucoside, confers protection against multiple oxidative damage related diseases. However, its efficacy and mechanism in HS induced intestinal injury remain poorly characterized. Therefore, a chronic HS mouse model with SA treatment was established to explore SA's intestinal protective effects and potential regulatory pathways. Our results revealed that chronic HS markedly suppressed growth performance, increased intestinal permeability, exacerbated oxidative stress, and disrupted intestinal mucosal structure. SA supplementation, especially at the dose of 20 mg·kg-1, partially rescued these pathological phenotypes, repaired mucosal morphology, alleviated oxidative damage, and inhibited epithelial apoptosis. Untargeted metabolomics demonstrated that HS and SA treatment induced differential metabolites and pathways were predominantly associated with mitochondrial function. With further mechanism exploration, the results showed that SA elevated the LC3-II/LC3-I ratio, reduced P62 abundance, and activated PINK1/Parkin mediated mitophagy. In summary, our results identify correlational linkage between SA intervention and the alleviation of chronic HS induced intestinal barrier dysfunction, which may be attributed to the recovery of mitochondrial homeostasis through PINK1/Parkin dependent mitophagy.