Lonicerin regulates AMPK/SIRT1/autophagy pathway to attenuate heat stress intestinal injury and inhibit inflammation

Intestinal injury is one of the most prevalent complications following heat stress (HS) in both humans and animals. Autophagy has been shown to maintain intestinal homeostasis, and modulation of autophagy may help alleviate intestinal injury caused by HS. Lonicerin (LN) are flavonoids known to have enhanced autophagy and anti-inflammatory effects. However, how LN prevent intestinal damage and regulate autophagy after HS remains unknown. The aim of this study was to elucidate the potential regulatory effects of LN on intestinal inflammation and intestinal barrier function in a HS model, and to elucidate the underlying molecular mechanisms. Firstly, we searched for the same inflammatory cytokines in the drug and disease targets through network pharmacology, and in vitro and in vivo experiments showed that LN significantly inhibited the production of pro-inflammatory cytokines. Then it was demonstrated that LN alleviates HS induced intestinal mucosal barrier damage by repairing tight junctions, goblet cells, and mucins in the colon of rats, consistent with the findings of in vitro experiments. In addition, LN reversed HS-induced reduced autophagic flux and maintained autophagic homeostasis via the AMP-activated protein kinase (AMPK)-Silent information regulator 1 (SIRT1) pathway in intestinal epithelial cells and intestinal system. In summary, this study demonstrated that LN exert intestinal protective and immunomodulatory effects by inhibiting the production of pro-inflammatory cytokines, maintaining the integrity of the intestinal mucosal barrier, and the level of AMPK-SIRT1 autophagy.