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

The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from <i>Myrica esculenta</i> bark, against diabetic nephropathy. Myr exhibited a significant hypoglycemic effect in high fat-fed and a single low-dose streptozotocin-induced type 2 d...

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Main Authors: Tarun K. Dua, Swarnalata Joardar, Pratik Chakraborty, Shovonlal Bhowmick, Achintya Saha, Vincenzo De Feo, Saikat Dewanjee
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/2/258
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author Tarun K. Dua
Swarnalata Joardar
Pratik Chakraborty
Shovonlal Bhowmick
Achintya Saha
Vincenzo De Feo
Saikat Dewanjee
author_facet Tarun K. Dua
Swarnalata Joardar
Pratik Chakraborty
Shovonlal Bhowmick
Achintya Saha
Vincenzo De Feo
Saikat Dewanjee
author_sort Tarun K. Dua
collection DOAJ
description The present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from <i>Myrica esculenta</i> 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.
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spelling doaj.art-922d2c3ffea441adad30fbaff323e2a92023-12-03T12:14:30ZengMDPI AGMolecules1420-30492021-01-0126225810.3390/molecules26020258Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing InflammationTarun K. Dua0Swarnalata Joardar1Pratik Chakraborty2Shovonlal Bhowmick3Achintya Saha4Vincenzo De Feo5Saikat Dewanjee6Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaDepartment of Chemical Technology, University of Calcutta, Kolkata 700009, IndiaDepartment of Chemical Technology, University of Calcutta, Kolkata 700009, IndiaDepartment of Pharmacy, University of Salerno, 84084 Fisciano, ItalyAdvanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, IndiaThe present study evaluated the therapeutic potential of myricitrin (Myr), a glycosyloxyflavone extracted from <i>Myrica esculenta</i> 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.https://www.mdpi.com/1420-3049/26/2/258diabetic nephropathyglucose utilizationinflammationoxidative stress<i>Myrica esculenta</i>myricitrin
spellingShingle Tarun K. Dua
Swarnalata Joardar
Pratik Chakraborty
Shovonlal Bhowmick
Achintya Saha
Vincenzo De Feo
Saikat Dewanjee
Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
Molecules
diabetic nephropathy
glucose utilization
inflammation
oxidative stress
<i>Myrica esculenta</i>
myricitrin
title Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
title_full Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
title_fullStr Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
title_full_unstemmed Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
title_short Myricitrin, a Glycosyloxyflavone in <i>Myrica esculenta</i> Bark Ameliorates Diabetic Nephropathy via Improving Glycemic Status, Reducing Oxidative Stress, and Suppressing Inflammation
title_sort myricitrin a glycosyloxyflavone in i myrica esculenta i bark ameliorates diabetic nephropathy via improving glycemic status reducing oxidative stress and suppressing inflammation
topic diabetic nephropathy
glucose utilization
inflammation
oxidative stress
<i>Myrica esculenta</i>
myricitrin
url https://www.mdpi.com/1420-3049/26/2/258
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