Synergistic anti-diabetic effect of phloroglucinol and total procyanidin dimer isolated from Vitisvinifera methanolic seed extract potentiates via suppressing oxidative stress: in-vitro evaluation studies

Diabetes is often associated with increased oxidative stress caused by an imbalance between detoxification and ROS production. Unfortunately, many commercial drugs available today for treating this disease have adverse side effects and ultimately fail to restore glucose homeostasis. Therefore, finding a dietary anti-diabetic remedy that is safe, effective, and economical is crucial. In this study, GC-MS analysis, subsequent HPLC-assisted fractionation, and SPE-based purification led to identifying and purifying of key components such as phloroglucinol and total procyanidin dimer (procyanidin dimer and procyanidin dimer gallate) from methanolic seed extract of Vitis vinifera. In-vitro anti-diabetic screening of various fractions derived from methanolic extract along with individual components and their combinations revealed the potential synergistic behaviour of phloroglucinol and total procyanidin dimer with the lowest IC50 of 48.21 +/- 3.54 mu g/mL for alpha-glucosidase and 63.06 +/- 5.38 mu g/mL for alpha-amylase inhibition which is found to be superior to the effect shown by the standard Epigallocatechin gallate. Later Glucose utilization studies demonstrated the concentration-dependent effect of Phloroglucinol and total procyanidin dimer, and that has raised the glucose uptake by approximately 36-57% in HepG2 cells and 35-58% in L6 myocytes over a concentration of 50-100 mu g/mL. The superior anti-diabetic effect of Phloroglucinol and total procyanidin dimer was proved by the suppression of oxidative stress with an IC50 of 7.92 +/- 0.36 mu g/mL for DPPH scavenging and 16.87 +/- 1.24 mu g/mL for SOD scavenging which is competent with the standard ascorbic acid. According to this study, suppressing ROS levels by phloroglucinol and total procyanidin dimer would be the underlying mechanism for the synergistic anti-diabetic effect of this combination.