Corilagin alleviates intestinal ischemia/reperfusion injury by relieving oxidative stress and apoptosis via AMPK/Sirt1-autophagy pathway

Abstract

Intestinal ischemia/reperfusion (II/R) injury is a common pathological process with high clinical morbidity and mortality. Autophagy plays an important role in the pathological development of II/R. Corilagin (CA) is a natural ellagitannin with various pharmacological effects such as autophagy regulation, antioxidant, and antiapoptosis. However, whether CA alleviates II/R injury is still unclear. In this study, we had found that CA significantly attenuated II/R induced intestinal tissue pathological damage, oxidative stress, and cell apoptosis in rats. Further studies showed that CA significantly promoted AMPK phosphorylation and sirt1 expression, and thus activated autophagy by upregulating protein expression of autophagy-related proteins Beclin1 and LC3II and promoting SQSTM1/P62 degradation both in vivo and in vitro. Inhibition of AMPK phosphorylation by its inhibitor compound C(CC) significantly abolished CA-mediated autophagy activation and the relievable effects on oxidative stress and apoptosis in vitro, suggesting the excellent protective activity of CA against II/R injury via AMPK/Sirt1-autophagy pathway. These findings confirmed the potent effects of CA against II/R injury, and provided novel insights into the mechanisms of the compound as a potential candidate for the treatment of II/R.

Corilagin attenuates airway inflammation and collagen deposition in ovalbumin-induced asthmatic mice

“…Several related genes, such as MMP series proteins and SMA, are affected by this signaling pathway. [18][19][20] However, some limitations were observed to this study, such as lack of detailed molecular mechanism analysis. Next, we should carefully analyze the downstream proteins of corilagin that inhibit progression of asthma through AMPK, which can be analyzed and identified by multi-omics (different omic groups) methods.…”

“…It exerts NF-κB inhibitory activity through phosphorylation of its downstream target proteins, thereby blocking the process of inflammatory response and alleviating asthma manifestations. 18 AMPK consists of a catalytic subunit and two regulatory subunits, which mainly regulate cellular energy metabolism. Emerging evidence supports that AMPK acts as a "metabolic brake" on energy-expenditure processes that drive inflammation and fibrosis.…”

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

“…Studies have found that selenium nanoparticles can effectively alleviate intestinal epithelial barrier damage by inhibiting autophagy mediated by the TBC1D15/Rab7 signaling pathway[ 45 ]. In contrast to the above studies, activation of the AMPK/ SIRT1-autophagy pathway alleviated intestinal I/R injury[ 46 , 47 ]. These studies seem to suggest that autophagic changes during the ischemic phase play a more decisive role in the course of the disease.…”

Ferritinophagy and Ferroptosis in Cerebral Ischemia Reperfusion Injury

“…Likewise, Oroxylin A, an active constituent of Scutellaria baicalensis, can regulate ferritinophagy and inhibit hepatic fibrosis via the cGAS-STING pathway [ 120 ]. In addition, some potent compounds, such as Corilagin, have anti-inflammatory and antioxidant effects [ 121 , 122 ], Wang et al found that Corilagin could inhibit NCOA4-mediated ferritinophagy, regulate iron homeostasis, inhibit ferroptosis, and attenuate intestinal ischemia/reperfusion injury (IIRI) in mice [ 123 ]. A coumarin derivative extracted from a variety of plants, Esculetin (6,7-dihydroxycoumarin), was shown to induce ferritinophagy in hepatocellular carcinoma cells through the NCOA4/LC3II/FTH1 pathway, promoting ferroptosis and exerting anticancer effects [ 124 ].…”