Chrysophanol alleviates myocardial injury in diabetic db/db mice by regulating the SIRT1/HMGB1/NF‑κB signaling pathway

Abstract

Myocardial injury induced by diabetes has become an increasing health problem. Chrysophanol (CHR) has been widely studied as a potential treatment for many diseases due to its anti-inflammatory effects, but has not been investigated in regard to diabetes-induced myocardial injury. The present study evaluated the myocardial protective effects of CHR in C57BL/KsJ-db/db diabetic mice. C57BL/KsJ-db/db and C57BLKS/J mice were treated with vehicle, metformin (100 mg/kg/day) or CHR (50 or 100 mg/kg/day) for 28 days. An oral glucose tolerance test was performed to detect blood glucose levels. Blood lipids, triglycerides, total cholesterol, myocardial function-associated enzymes, namely creatine kinase (CK) and lactate dehydrogenase (LDH), and insulin levels were analyzed. TNF-α, interleukin (IL)-1β and IL-6 inflammatory cytokine levels in serum and myocardial tissues were determined by ELISA. Expression of silent information regulator l (SIRT1) and high mobility group box 1/NF-κB pathway-associated proteins in myocardial tissues were measured by western blot analysis and immunohistochemistry. CHR treatment at both concentrations markedly decreased blood lipid and serum insulin levels, and inhibited the myocardial enzymes CK and LDH. CHR also significantly ameliorated the cardiac pathological changes in diabetic mice. The inflammatory cytokine levels that were increased in C57BL/KsJ-db/db diabetic mice were downregulated by CHR treatment. CHR also increased SIRT1 protein expression and inhibited activation of the HMGB1/NF-κB pathway. In conclusion, the present study indicates that CHR effectively protected against diabetic myocardial injury via regulation of SIRT1 and the HMGB1/NF-κB signaling pathway.

<p>Chrysophanol Inhibits the Progression of Diabetic Nephropathy via Inactivation of TGF-β Pathway</p>

“…Meanwhile, CHR could protect diabetic mice from myocardial injury via mediation of SIRT1/HMGB1/ NF-κB signaling pathway. 16 However, our current study found CHR could mediate TGF-β signaling in DN. The difference may due to different types of diabetes complications.…”

MiR-217 inhibition relieves oxidative stress-induced melanocyte damage by targeting sirtuin 1

“…Oxidative stress stimulates NF-jB and causes translocation of NF-jB to the nucleus [37]. In addition, there are studies shown that SIRT1 affects NF-jB signalling pathway [38][39]. So we next detect whether miR-217 affects NF-jB signalling pathway through regulating SIRT1 and then plays important roles in H 2 O 2 -treated melanocytes.…”

Evaluating the antidiabetic effects of R-verapamil in type 1 and type 2 diabetes mellitus mouse models

“…Systemic inflammation is often associated with obesity/insulin resistance, T1DM, and T2DM [51][52][53]. DM animal models such as STZinduced and db/db mice presented with upregulated proinflammatory cytokines such as TNF-α, IL-6, and IL-1β compared to normal mice [36,54]. Diabetes-induced myocardial injury was highly correlated with serum and myocardial proinflammatory cytokines [54].…”