Phenolic enriched fraction of Clerodendrum glandulosum Lindl. leaf extract ameliorates hyperglycemia and oxidative stress in streptozotocin-nicotinamide induced diabetic rats

Abstract

Background

Clerodendrum glandulosum Lindl. is an important ethnomedicinal shrub of Northeast India, used by traditional healers to control various ailments like diabetes, hypertension, arthritis, etc.

Objectives

The present study was conducted to explore the anti-hyperglycemic and antioxidative effects of the polyphenol-rich fraction (PRF) of C. glandulosum leaf extract and identification of its major bioactive compounds. Further, an in-silico molecular docking study was also performed to understand the molecular interactions of the identified major compounds with some target proteins associated with diabetic complications.

Materials and methods

PRF was purified from the hydromethanolic (80% MeOH) extract of leaves and subjected to assessment of in-vitro antioxidant and anti-diabetic properties. It was also subjected to evaluate the ameliorative effect during streptozotocin-nicotinamide-induced hyperglycemia in Wistar albino rats. An in-silico molecular docking study was also performed to complement the in-vitro/in-vivo studies.

Results

Chemical analysis of PRF showed the presence of phenolics like caffeic acid, verbascoside, isoverbascoside, and apigenin, of which verbascoside (598.14 ± 1.24 mg/g) was found to be the principal compound. In-vitro studies showed potent antioxidant (IC₅₀ of DPPH:32.45 ± 2.16 μg/mL; ABTS:39.08 ± 0.53 μg/mL) properties and excellent aldose reductase inhibition potential (IC₅₀ 2.18 ± 0.10 μg/mL). Treatment with PRF showed reduced blood glucose levels and increased plasma insulin levels. The results also indicate an improvement of endogenous antioxidants and suppression of inflammatory cytokines (IL-6 and TNF-α) comparable to the standard. Molecular docking studies predicted promising interactions between the identified molecules and the crucial amino acid residues of the enzymes involved in the development of hyperglycemia.

Conclusion

This study revealed the antihyperglycemic and antioxidant potential of partially purified fraction PRF of C. glandulosum leaves.