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J Herbmed Pharmacol. 2021;10(3): 304-312.
doi: 10.34172/jhp.2021.35
  Abstract View: 204
  PDF Download: 223

Original Article

In vitro anti-diabetic activity, bioactive constituents, and molecular modeling studies with sulfonylurea receptor1 for insulin secretagogue activity of seed extract of Syzygium cumini (L.)

Meharban Assan Aliyar 1 ORCID logo, Pratibha Nadig 1* ORCID logo, Nagakumar Bharatham 2 ORCID logo

1 Department of Pharmacology, Vydehi Institute of Medical Sciences and Research Centre, Bangalore 560066, Karnataka, India
2 Bugworks research India Pvt.Ltd, Center for Cellular & Molecular Platforms, National Center for Biological Sciences, TIFR GKVK Campus, Bellary Road, Bangalore 560 065, India

Abstract

Introduction: Syzygium cumini (L.) has been known to be used for diabetes treatment in traditional Indian and Chinese medicine. The present study focuses on the evaluation for glucose uptake and insulin release in vitro and characterization of phytoconstituents of the hydro-ethanolic extract of Syzygium cumini seed (SCE). Further, this report covers the molecular docking findings of the bioactive constituents on the sulfonylurea receptor 1 (SUR1). Methods: A glucose uptake assay of SCE was used to estimate the glucose uptake from the cell lysates and the cell culture supernatants using insulin as the reference standard. Insulin release activity of SCE from RIN-5F cells was estimated using enzyme-linked immunosorbent assay. The phytoconstituents were isolated by preparative HPLC and characterized by mass spectrometry, nuclear magnetic resonance (NMR) and infrared spectroscopy. The molecular docking of bioactive constituents was carried on repaglinide bound to the SUR1. Results: In the presence of SCE, the glucose uptake through L6 myoblast cells increased by 19.91% at 40 µg/mL in comparison with the vehicle control (P < 0.05). Moreover, SCE showed 2.8-fold enhancement of insulin release at 40 µg/mL as compared to the vehicle controls (P < 0.05). Gallic and ellagic acids were the key phytoconstituents isolated from SCE. Molecular docking studies revealed that both gallic acid and ellagic acid bind to the repaglinide binding pocket of SUR1. Conclusion: SCE increases the release of insulin and enhances glucose uptake in vitro, which may contribute to its in vivo anti-diabetic activity. The presence of ellagic acid and gallic acid in SCE may be the cause for enhanced insulin release observed with SCE following binding to SUR1.
Keywords: Molecular docking, NMR spectroscopy, Gallic acid, Ellagic acid, RIN-5F cells, L6 myoblasts
Syzygium cumini increased the release of insulin and enhanced glucose uptake in vitro. The research is relevant to public health because it focuses on the mechanism of insulin secretion and its relevance for type-2 diabetes treatment.
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Submitted: 04 Dec 2020
Revision: 04 Jan 2021
Accepted: 05 Feb 2021
ePublished: 02 Jul 2021
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