Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.

Kalathookunnel Antony Antu,Karunakaran S Anilkumar,Akhilesh K Tamrakar,Arvind Mishra,Chandrasekharan K Chandrakanth,K Gopalan Raghu,Arvind K Srivastava,Mariam Philip Riya,Hitoshi Ashida

doi:10.1371/journal.pone.0105829

Abstract

The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of ‘Nisakathakadi’ an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.

Highlights

Diabetes mellitus is a global health threat associated with increased morbidity, mortality and poor quality of life which is characterized by chronic hyperglycemia [1]
Phytochemical characterization HPLC analysis confirmed the presence of beta-sitosterol
To date many antidiabetic medicinal plants have been reported only a small number of these have received scientific evaluation to elucidate their mechanism of action

Summary

Introduction

Diabetes mellitus is a global health threat associated with increased morbidity, mortality and poor quality of life which is characterized by chronic hyperglycemia [1]. Hyperglycemia leads to vascular complications via glucose toxicity and oxidative stress [2] and its proper control is an important therapeutic strategy to prevent diabetic complications [3]. A medication that can address these abnormalities along with oxidative stress may be quite beneficial to diabetes. Current therapies include insulin and various oral agents such as sulfonylureas, biguanides, alpha-glucosidase inhibitors and gliptins, which are used as monotherapy or in combination to achieve better glycemic regulation [3]. These medications have some undesirable effects [5] and managing diabetes without side effects is still being a challenge. The search for more effective and safer therapeutic agents of natural origin has been found to be valuable

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