Sinomenine pretreatment alleviates hepatic ischemia/reperfusion injury through activating Nrf‐2/HO‐1 pathway

Abstract

Introduction Ischemia–reperfusion (IR) injury is induced by an interrupted blood flow and succeeding blood restoration, which is common in the operation of liver transplantation. Serious IR injury is a major reason leading to transplant failure. Hepatic IR is featured by excessive inflammatory response, oxidative stress, and apoptosis. Sinomenine (SIN) is derived from the herb Sinomeniumacutum and shows properties of anti‐inflammation and antiapoptosis in multiple IR‐induced organ injuries. However, the effect of SIN in hepatic IR has not been investigated. Methods This study aims to investigate impacts of SIN on hepatic IR and the involved signaling pathway. An in vivo rat model of syngeneic orthotopic liver transplantation was constructed to induce the hepatic IR injury. Results Results showed that SIN pretreatment provided a significant prevention against IR‐induced hepatic injury as manifested by the downregulated activities of serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, the alleviatedoxidative stress as shown by increased activities of serum superoxide dismutase and glutathione peroxidase, and decreased serum level of malondialdehyde, the suppressed inflammatory responses as shown by downregulated serum tumor necrosis factor‐α, interleukin (IL)‐6, IL‐8 levels, and upregulated IL‐10 level, as well as attenuated apoptosis as shown by decreased protein expression of cleaved caspase‐3 and −9. In line with these results, SIN pretreatment also alleviatedthe hepatic histopathological changes in IR rats and induced Nrf‐2/HO‐1 activation. The use of brusatol, a selective inhibitor for Nrf‐2, effectively reversed SIN‐induced above effects. Conclusions Altogether, our results demonstrate that SIN might be a useful therapeutic drug for preventing hepatic IR‐induced injury during clinical liver transplantation.

High‐dose sinomenine attenuates ischemia/reperfusion‐induced hepatic inflammation and oxidative stress in rats with diabetes mellitus

“…The dose of SIN was selected based on several previously published studies. 17 , 21 Rats in group I and II were injected with normal sterile saline at the same frequency. Rats received daily i.p.…”

“…Hepatic I/R was induced based on a previous research. 17 In brief, hepatic ischemia was created by using a microvascular clip and lasted for 1 h, as confirmed by the pale appearance of the clamped lobes. The clip was then discreetly displaced to permit a 3‐h blood reperfusion.…”

“… 13 SIN alleviates diabetic peripheral neuropathic pain, 14 , 15 and confers cognitive protection by curtailing hippocampal neuron ferroptosis. 16 Moreover, SIN has been found to play significant protective roles against I/R‐induced multiple organ injuries, including the liver, 17 brain, 18 heart, 19 and kidney. 20 However, whether SIN also exerts protective effects in diabetic rats with hepatic I/R injury has never been explored.…”

“…20 However, whether SIN also exerts protective effects in diabetic rats with hepatic I/R injury has never been explored. Based on our previous results that SIN could attenuate I/R‐induced hepatic injury in healthy rats, 17 this study aims to further detect if SIN could also serve a protective role in diabetes rats after hepatic I/R and what's the underlying mechanism. Considering diabetes is reaching epidemic levels among the adult population, clarificating this question would greatly reveal the preventive value of SIN in clinical practice.…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…Z.G. Yang et al reported that SIN inhibited oxidative stress and inflammatory responses by promoting Nrf-2/HO-1 signaling activation, thereby ameliorating inflammation by increasing TNF-α, IL-6, and IL-8 and decreasing IL-10 [ 208 ]. Y. Li et al demonstrated the protective effect of SH on liver injury induced by Pb.…”