Ursolic acid alleviates heat stress-induced lung injury by regulating endoplasmic reticulum stress signaling in mice.

作者：Ying Yang, Chang-Wu Li, Ning Liu, Mengmeng Wang, Xiumin Zhou, I. Kim, Zhenlong Wu · 发表于：Journal of Nutritional Biochemistry · 年份：2020 · DOI：10.1016/j.jnutbio.2020.108557 · 被引用次数：26 · 研究领域：Medicine、Chemistry

Acute lung injury has been reported to be associated with heat stress in various animals. Ursolic acid is a natural pentacyclic triterpenoid compound with multiple bioactivities. However, it remains unknown whether ursolic acid supplementation alleviates heat stress-induced lung injury. In the present study, male Institute of Cancer Research (ICR) mice were left untreated under a normal temperature condidtion (23 ±1°C), receiving orally administrated with vehicle (phosphate buffered saline) or ursolic acid (40 mg/kg BW -1 • d-1 for 2 d), and then were subjected to high temperature (41 ± 1°C) for 2 h. Histological alterations, activities of anti-oxidative enzymes, apoptosis, generation of reactive oxygen species, abundance of inflammatory cytokines and endoplasmic reticulum stress-related proteins were analyzed. Compared with the controls, heat stress treatment led to enhanced apoptosis, increased H2O2 production, and upregulated protein levels of inflammatory cytokines in the serum, including TNF-α, IL-6, and IL-1β. Activities of MDA, LDH, and MPO were increased, while the activities for SOD and CAT were reduced in lung tissues of mice. All these alterations were significantly prevented by ursolic acid administration. Further study showed that heat stress led to activation of PERK-eIF2α-CHOP signaling, which was attenuated by ursolic acid supplementation. These findings indicated that ursolic acid pretreatment protected lung tissues against heat stress-induced injury by regul...