Bilal Aslam - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Asif Hussain - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Muhammad Faisal - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Shaneel Kousar - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Alishbah Roobi - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Muhammad Sajid - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan
Aneela Gul - Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad-۳۸۰۴۰, Faisalabad, Punjab, Pakistan

Objective(s): This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model.Materials and Methods: In vitro, HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo, acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=۶) were orally treated with PHE (۲۰۰, ۴۰۰, and ۶۰۰ mg/kg/day) and glibenclamide (GLB; ۱۰ mg/kg/day) for six consecutive weeks. Then, biochemical biomarkers, oxidative stress parameters, histopathological examination, and mRNA expression levels (RT-qPCR) were determined.Results: The presence of polyphenols in PHE was confirmed in correlation to marked DPPH scavenging (IC۵۰: ۱.۶۰ mg/ml) and α-amylase inhibition (IC۵۰: ۰.۸۲ mg/ml). PHE demonstrated no toxicity in rats up to a dose of ۲۰۰۰ mg/kg. In diabetic rats, PHE dose-dependently ameliorated the serum levels of glucose, insulin, glycated hemoglobin A۱c (HbA۱c), leptin, and glucokinase (GCK). Also, PHE substantially alleviated serum inflammatory markers (TNF-α and CRP) and oxidative stress indicators (MDA, SOD, and CAT) in pancreatic tissues. PHE, particularly at ۶۰۰ mg/kg, attenuated cellular oxidative stress via modulating the mRNA expression levels of genes regulating MAPK/JNK (Mapk-۸, Traf-۴, and Traf-۶) and Nrf-۲/Keap-۱ pathways and promoted insulin signaling through up-regulating insulin signaling cascade (Pdx-۱, Ins-۱, and Ins-۲), as compared to GLB. Furthermore, histopathological findings supported the aforementioned results.Conclusion: Our study suggests that polyherbal extract has promising antioxidant and antidiabetic activities by modulating the MAPK/JNK, Nrf-۲/Keap-۱, and insulin signaling pathways.

alpha-amylase, Anti-oxidant, Hyperglycemia, Oxidative stress, Polyherbal extract