Pterostilbene Prevents Tunicamycin-Induced Intestinal Barrier Damage by Targeting Endoplasmic Reticulum Stress, Oxidative Stress, Autophagy, and Gut Microbiota

Endoplasmic reticulum (ER) stress is a crucial factor in the pathogenesis of intestinal diseases. Pterostilbene (PT) has been demonstrated to mitigate ER stress and protect against intestinal disorders. Here, we investigated the effects of PT on tunicamycin (TM)-induced intestinal ER stress and intestinal barrier damage in vivo in piglets and in vitro in intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cells. Results indicated that PT prevented TM-induced body weight loss (−0.67 ± 0.16 vs −0.48 ± 0.08 kg) and improved intestinal barrier integrity and goblet cell function of the TM-challenged piglets (P < 0.05). PT also inhibited ER stress, restored redox homeostasis and autophagic flux, and decreased apoptosis in the TM-challenged jejunum and the TM-exposed IPEC-J2 cells (P < 0.05). However, these attenuating effects of PT in the TM-treated IPEC-J2 cells were blunted by the knockdown of sirtuin 1 (P < 0.05). Moreover, PT increased the Ace index (390.12 ± 60.05 vs 460.27 ± 42.83) and downregulated the prevalence of the phylum Proteobacteria (48.73% ± 12.62% vs 32.10% ± 11.08%) of cecal microbiota of the TM-challenged piglets (P < 0.05). In conclusion, PT alleviated TM-induced intestinal barrier damage by regulating ER homeostasis, oxidative stress, autophagic flux, and gut microbiota.