Acacia nilotica polyphenol extract restores glucose homeostasis by upregulating the insulin secretion and lowering the oxidative stress through down regulation of c-Jun N-terminal kinase (JNK) signaling cascade

摘要

ObjectivesAcacia nilotica(A. nilotica) has been used in ayurvedic system of medicine for the treatment of numerous metabolic disorders from decades. Despite its wide usage in traditional medicine system, to our knowledge, little attention has been given to the mechanisms involved in therapeutic potential ofA. nilotica.The pupose of our study was to understand the molecular and biochemical mechanisms involved in protective effect ofA. niloticapolyphenol extract (A. niloticaPPE) on diabetes induced by alloxan monohydrate.MethodsTotal polyphenols and total flavonoids inA. niloticaPPE were determined using Folin-Ciocalteu method and Aluminiun Chloride colorimetric method respectively. HPLC analysis ofA. niloticaPPE was performed to determine the phenolic contents. Antidiabetic potential ofA. niloticaPPE was evaluated through biochemical (FBG, serum glucose, serum insulin, HbA1c, serum C-peptide), antioxidant defense markers, Intracellular ROS and lipid peroxidation measurements as well as histopathological analysis. qRT-PCR analysis was also executed to measure the expression level of numerous genes involved in insulin signaling cascade (Pdx-1, ngn-3, Ins-1, GLUT-4, IRS-1) and c-Jun N-terminal kinase (JNK) downstream cascade (MAPK-8, Traf-4 & Traf-6) to determine the main molecular mechanisms involved in antidiabetic potential ofA. niloticaPPE.ResultsResults of the study have confirmed the presence of total polyphenolic (61.17?mg GAE/g) and total flavonoid (53.12?mg CE/g) contents inA. niloticaPPE. HPLC assay ofA.niloticaPPE revealed the presence of quercitin, gallic acid, chlorogenicacid, Kaempferol and catechin.A. niloticaPPE significantly inverted the hyperglycemia by reducing the FBG, serum glucose, HbA1c levels and improving the insulin & C-peptide levels.A. niloticaPPE improved the antioxidant defense markers (SOD, CAT, GPx, GSH) and reduced the intracellular ROS and TBARS levels. Alloxan induced histological changes were also recovered in extract treated groups.A. niloticaPPE upregulated the expressions of Pdx-1, ngn-3, Ins-1, GLUT-4, IRS-1 and downregulated the expressions of MAPK-8, Traf-4 & Traf-6 genes.ConclusionIn a nutshell,A. niloticaPPE can be used as a better therapeutic approach for the management of both type 1 and type 2 diabetes as it may improve the beta cells regeneration, biochemical indicators and reduce the cellular stress.