Protective effect of dioscin against intestinal ischemia/reperfusion injury via adjusting miR-351-5p-mediated oxidative stress
Authors: Xufeng Tao
Pengyuan Sun
Zhang Mao
Yan Qi
Yupeng Hu
Zeyao Tang
Jinyong Peng
Lianhong Yin
Lina Xu
Journal: Pharmacological Research (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Dioscin; Intestinal ischemia/reperfusion; Oxidative stress; miR-351-5p/Sirt6 signal pathway.
Affiliations: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China., College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China. Electronic address: .

Abstract:  Oxidative stress plays important roles in intestinal ischemia-reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating oxidative stress is necessary. In this study, the effects and possible mechanisms of dioscin against hypoxia-reoxygenation (H/R) injury in IEC-6 cells and II/R injury in mice were investigated. The results showed that dioscin markedly increased cell viability, and reduced ROS level caused by H/R injury in IEC-6 cells. in vivo, dioscin significantly reduced the levels of MDA, MPO and chiu' score, increased SOD level, and improved pathological changes caused by II/R injury in mice. Mechanism investigation showed that dioscin markedly up-regulated the expression levels of Sirt6 by decreasing miR-351-5p levels, decreased the expression levels of p-FoxO3α via activating AMPK, and increased the expression levels of MnSOD and CAT. In addition, miR-351-5p mimic in IEC-6 cells and agomir in mice increased ROS levels and aggravated II/R injury. MiR-351-5p inhibitor in IEC-6 cells and antagomir in mice alleviated these actions by adjusting Sirt6 signal pathway. MiR-351-5p interference experiment further confirmed that dioscin increased Sirt6 expression level by down- regulating miR-351-5p level to inhibit oxidative stress and reduce II/R injury. Furthermore, we also demonstrated that dioscin inhibited the expression level of miR-351-5p via reducing TRBP expression level during the generation of miR-351-5p mature body. Dioscin showed protective effect against II/R injury via adjusting miR- 351-5/Sirt6 signal to reduce oxidative stress, which should be considered as one potent candidate to treat II/R injury. In addition, miR-351-5/Sirt6 could be one effective drug target against II/R injury. 

Retracted: No

PubPeer comments:
 August 2019  The authors have realised an error in Fig. 4B where incorrect lanes for GAPDH and CAT were mistakenly uploaded. We now provide an amended version of Fig 4B with the correct GAPDH and CAT lanes. The authors apologize for any inconvenience to readers arising from their error. ![file] , 
 Figures 2 and 5 appear to have a duplicated image. *** ![file] , 
 December 2021 The authors regret that in the article referenced above during the course of revision we uploaded wrong images for ROS levels of u201cH R + Dioscin 6.25u2033 group in Fig. 2A. We now provide the correct images for Fig. 2A, which confirm the results as we originally described them. All authors have agreed to the correction. The authors would like to apologise for any inconvenience caused. ![file] ,