Effects of emodin on intestinal mucosal barrier by the upregulation of miR-218a-5p expression in rats with acute necrotizing pancreatitis

Abstract

Emodin is an effective component in rhubarb to cure intestinal dysfunction, but the specific mechanism remains unknown. This study aimed to evaluate the protective effects of emodin on intestinal dysfunction caused by acute severe pancreatitis and reveal the functional mechanism of emodin in the treatment of this condition. An acute severe pancreatitis model was prepared using taurocholate. In the treatment group, 50 mg/kg emodin was injected intravenously 2 h before the induction of acute severe pancreatitis at an interval of 8 h. After 24 h, the gene expression and protein levels of miR-218a-5p, RhoA, ROCK1, Akt, Notch1, Bax, Bcl-2, Fas, FasL, caspase-3, and caspase-9 were determined through reverse transcription polymerase chain reaction and Western blot analysis. The protein levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract were also determined through Western blot analysis. The effects of miR-218a-5p on the apoptosis of rat intestinal epithelial cell-18 were observed through flow cytometry. The effects of emodin on intestinal cell apoptosis induced by acute severe pancreatitis were observed via TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling). Pathological changes in the pancreas and intestine of rats in each group were observed through hematoxylin and eosin staining. After 24 h of acute severe pancreatitis induced by taurocholate, emodin reduced the expression of miR-218a-5p in the intestinal tract; increased the expression of Notch1 and Bcl-2; decreased the expression levels of RhoA, ROCK1, Akt, Bax, Fas, FasL, caspase-3, and caspase-9; inhibited the intestinal cell apoptosis caused by acute severe pancreatitis; increased the protein expression levels of occludin, zonula occludens-1 (ZO-1), and E-cadherin in the intestinal tract; and alleviated intestinal dysfunction caused by acute severe pancreatitis. Emodin could regulate Notch1 and RhoA/ROCK pathways by regulating the miR-218a-5p expression in the intestine. It could also inhibit intestinal cell apoptosis induced by acute severe pancreatitis and improve the intestinal dysfunction caused by severe acute pancreatitis.

Emodin Protects Sepsis Associated Damage to the Intestinal Mucosal Barrier Through the VDR/ Nrf2 /HO-1 Pathway

“…Studies have shown that emodin is a potential candidate drug for the treatment of sepsis associated intestinal mucosal injury (Ning et al, 2017;Tan et al, 2020). However, the underlying mechanism of emodin's pharmacological activity is still not fully understood.…”

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway

“…SAP is a dangerous acute abdominal disease that is usually complicated by multiple organ injury[ 18 ]. The small intestine is most frequently affected by SAP[ 19 , 20 ]. In the present study, we found that rats with SAP exhibited serious pancreatic injury and changes in the structure of the small intestine mucosa, which is consistent with previous research[ 21 , 22 ].…”

Effects of Anthraquinones on Immune Responses and Inflammatory Diseases

“…Total AQs significantly decreased the activation of NLRP3 inflammasome, the number of Tregs and the ratio of Th1/Th2, while significantly increasing the expression of sIgA in the intestinal tissues [78]. A main component of total free AQs, emodin, inhibited the expression of miR-218a-5p and thus the activation of Notch1 and RhoA/ROCK pathways in the intestine, which may partially explained the effect of emodin on intestinal dysfunction caused by severe acute pancreatitis [79].…”