Anti-inflammatory and Anti-endoplasmic reticulum stress Effects of catalpol Against myocardial ischemia-reperfusion injury in streptozotocin-induced diabetic rats.

Fangjie Bi,Yujia Xu,Guangxin Chen,Pan Wang

doi:10.1590/0001-3765202020191148

Fangjie Bi, Yujia Xu + Show 2 more

Open Access

https://doi.org/10.1590/0001-3765202020191148

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Abstract

The current study was designed to investigate the effects and the mechanism of catalpol on myocardial ischemia-reperfusion (MI/R) injury in a diabetic rat model. Male Sprague-Dawley rats were divided into DM + sham, DM +I/R, and DM +I/R + C groups and diabetes was induced using single injections of streptozotocin (STZ; 70 mg/kg; i.p). After confirming the induction of diabetes, rats were administered physiological saline and catalpol (10 mg/kg; i.p.) daily for 28 days. Subsequently, rats were subjected to left anterior descending (LAD) coronary artery occlusion for 30 min followed by reperfusion for 2 h. Haemodynamic parameters were recorded throughout surgery, and following sacrifice, hearts were isolated for biochemical, histopathological, and molecular analyses. Catalpol treatment significantly ameliorated MI/R injury by improving cardiac function, normalizing myocardial enzyme activities and markers of oxidative stress, and by maintaining myocardial architecture. Furthermore, expression levels of the inﬂammatory cytokines TNF-α and IL-6 were decreased in biochemical and immunohistochemical studies. Additionally, the cardioprotective effects of catalpol were partly related to reductions in myocardial endoplasmic reticulum stress (ERS). In conclusion, catalpol exerts cardioprotective effects in diabetic rats by attenuating inﬂammation and inhibiting ERS.

Highlights

Diabetes mellitus (DM) is known to increase the risk of cardiovascular complications and seriously affects human health
We investigated the protective effects of catalpol following myocardial ischemia-reperfusion (MI/R) injury in diabetic rats and determined whether these benefits were associated with the inhibition of inflammation and attenuation of endoplasmic reticulum stress (ERS)
Primary antibodies against interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), glucose regulated protein 78 (GRP78), PKR-like endoplasmic reticulum (ER) kinase (PERK), P-PERK, eukaryotic initiation factor-2α, P-eIF2a, Caspase-12 and nicotinamide adenine dinucleotide phosphate (NAPDH) were procured from Santa Cruz Biotechnology (CA, USA)

Summary

Introduction

Diabetes mellitus (DM) is known to increase the risk of cardiovascular complications and seriously affects human health. Identification of new approaches for protecting against diabetic heart diseases and alleviating MI/R insults is a major priority. Accumulating evidence indicates that inflammation and endoplasmic reticulum stress (ERS) play important roles in the MI/R related injury (Gao et al 2017, Zhang et al 2017). Strategies that inhibit inflammation and attenuate ERS may have therapeutic potential. Rehmanniae glutinosa L. is widely used traditional Chinese medicine, and catalpol is the the main bioactive component in the roots of Rehmannia glutinosa (Zhang et al 2008). A growing body of evidence has shown that catalpol has multiple biological effects, and its anti-inflammatory, anti-diabetic and anti-ERS activities are increasingly considered as central to the protective effects of catalpol

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