Myricitrin, a Glycosyloxyflavone in Myrica esculenta Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation.

Tarun K Dua,Shovonlal Bhowmick,Vincenzo De Feo,Saikat Dewanjee,Achintya Saha,Swarnalata Joardar,Pratik Chakraborty

doi:10.3390/molecules26020258

Abstract

The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from Myrica esculenta bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 diabetic (T2D) rats. Myr was found to improve glucose uptake by the skeletal muscle via activating IRS-1/PI3K/Akt/GLUT4 signaling in vitro and in vivo. Myr significantly attenuated high glucose (HG)-induced toxicity in NRK cells and in the kidneys of T2D rats. In this study, hyperglycemia caused nephrotoxicity via endorsing oxidative stress and inflammation resulting in the induction of apoptosis, fibrosis, and inflammatory damages. Myr was found to attenuate oxidative stress via scavenging/neutralizing oxidative radicals and improving endogenous redox defense through Nrf-2 activation in both in vitro and in vivo systems. Myr was also found to attenuate diabetes-triggered renal inflammation via suppressing NF-κB activation. Myr inhibited hyperglycemia-induced apoptosis and fibrosis in renal cells evidenced by the changes in the expressions of the apoptotic and fibrotic factors. The molecular docking predicted the interactions between Myr and different signal proteins. An in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) study predicted the drug-likeness character of Myr. Results suggested the possibility of Myr to be a potential therapeutic agent for diabetic nephropathy in the future.

Highlights

Type 2 diabetes mellitus (T2D) is a chronic metabolic syndrome accounting for 90–95%
Diabetic nephropathy or diabetic kidney disease is the most common T2D complication affecting around 40% of T2D patients [5]
We evaluated the protective effect of Myr, a natural antioxidant in M. esculenta bark, against T2D and associated diabetic nephropathy

Summary

Introduction

Type 2 diabetes mellitus (T2D) is a chronic metabolic syndrome accounting for 90–95%of the total diagnosed cases of diabetes mellitus [1]. The number of T2D cases is increasing steadily around the world [2]. It is characterized by hyperglycemia which is caused due to the establishment of insulin resistance, decrease in insulin production, and eventually loss of β-cell function [3]. Diabetic nephropathy or diabetic kidney disease is the most common. Diabetic nephropathy is a multifunctional degenerative syndrome characterized by albuminuria, glomerular lesions, Molecules 2021, 26, 258 major causes of mortality in T2D [4]. Diabetic nephropathy or diabetic kidney disease is the most common T2D complication affecting around 40% of T2D patients [5]. Diabetic nephropathy is a multifunctional degenerative syndrome characterized by albuminuria, glomerular lesions, tubulointerstitial fibrosis, and loss of renal filtration rate.

Methods

Results

Conclusion