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

Abstract

Objectives: Acacia 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 of A. nilotica. The pupose of our study was to understand the molecular and biochemical mechanisms involved in protective effect of A. nilotica polyphenol extract (A. nilotica PPE) on diabetes induced by alloxan monohydrate. Methods: Total polyphenols and total flavonoids in A. nilotica PPE were determined using Folin-Ciocalteu method and Aluminiun Chloride colorimetric method respectively. HPLC analysis of A. nilotica PPE was performed to determine the phenolic contents. Antidiabetic potential of A. nilotica PPE 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 of A. nilotica PPE. Results: Results of the study have confirmed the presence of total polyphenolic (61.17 mg GAE/g) and total flavonoid (53.12 mg CE/g) contents in A. nilotica PPE. HPLC assay of A.nilotica PPE revealed the presence of quercitin, gallic acid, chlorogenic acid, Kaempferol and catechin. A. nilotica PPE significantly inverted the hyperglycemia by reducing the FBG, serum glucose, HbA1c levels and improving the insulin & C-peptide levels. A. nilotica PPE 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. nilotica PPE 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. Conclusion: In a nutshell, A. nilotica PPE 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.

Keywords

• A. nilotica PPE
• HPLC
• Insulin signaling pathway
• JNK pathway
• GLUT-4
• ROS