Phenolics Profiling of Carpobrotus edulis (L.) N.E.Br. and Insights into Molecular Dynamics of Their Significance in Type 2 Diabetes Therapy and Its Retinopathy Complication

Saheed Sabiu,Fatai O Balogun,Stephen O Amoo

doi:10.3390/molecules26164867

Abstract

Adverse effects associated with synthetic drugs in diabetes therapy has prompted the search for novel natural lead compounds with little or no side effects. Effects of phenolic compounds from Carpobrotus edulis on carbohydrate-metabolizing enzymes through in vitro and in silico methods were assessed. Based on the half-maximal inhibitory concentrations (IC50), the phenolic extract of the plant had significant (p < 0.05) in vitro inhibitory effect on the specific activity of alpha-amylase (0.51 mg/mL), alpha-glucosidase (0.062 mg/mL) and aldose reductase (0.75 mg/mL), compared with the reference standards (0.55, 0.72 and 7.05 mg/mL, respectively). Molecular interactions established between the 11 phenolic compounds identifiable from the HPLC chromatogram of the extract and active site residues of the enzymes revealed higher binding affinity and more structural compactness with procyanidin (−69.834 ± 6.574 kcal/mol) and 1,3-dicaffeoxyl quinic acid (−42.630 ± 4.076 kcal/mol) as potential inhibitors of alpha-amylase and alpha-glucosidase, respectively, while isorhamnetin-3-O-rutinoside (−45.398 ± 4.568 kcal/mol) and luteolin-7-O-beta-d-glucoside (−45.102 ± 4.024 kcal/mol) for aldose reductase relative to respective reference standards. Put together, the findings are suggestive of the compounds as potential constituents of C. edulis phenolic extract responsible for the significant hypoglycemic effect in vitro; hence, they could be exploited in the development of novel therapeutic agents for type-2 diabetes and its retinopathy complication.

Highlights

Diabetes, one of the leading causes of death globally, is a chronic metabolic derangement leading to high levels of glucose in systemic circulation due to the inability of the body to manage available glucose levels, arising from ineffective or insensitive insulin secretion by islets of Langerhans beta cells of the pancreas [1]
Based on the standards used for the HPLC analysis, 11 major phenolic compounds including sinapic acid, cacticin, hyperoside, 1,3-dicaffeoxyl quinnic acid, procyanidin, luteolin-7-O-beta-D-glucoside, rutin, epicatechin, isorhamnetin-3-O-rutinoside, chlorogenic acid and myricetin were identified from the chromatogram of the extract (Figure 1, Table 1)
It is noteworthy that the prominent peaks as observed from the chromatogram with their highest relative abundances were for chlorogenic acid followed by rutin, luteolin-7-O-beta-D-glucoside and epicatechin, suggesting they are the major identifiable phenolic constituents of C. edulis (Figure 1)

Summary

Introduction

One of the leading causes of death globally, is a chronic metabolic derangement leading to high levels of glucose in systemic circulation (hyperglycaemia) due to the inability of the body to manage available glucose levels, arising from ineffective or insensitive insulin secretion by islets of Langerhans beta cells of the pancreas [1]. Glycaemic control remains one of the therapeutic approaches to hyperglycaemia and the risk of developing complications, and this has been achieved through lifestyle modification and conventional oral hypoglycaemic drugs [4] Drugs such as acarbose and other α-glucosidase inhibitors have been identified as therapeutic agents against the key enzymes implicated in carbohydrate metabolism in the gastrointestinal tract, the associated adverse effects as evident in increased postprandial blood glucose level in diabetics have undermined their application [5]. The occurrence of adverse effects is consistent with synthetic inhibitors of aldose reductase, a major enzyme of the polyol pathway and a drug target in the clinical treatment of retinopathy complication of type 2 diabetes mellitus [6]. The pharmacological use of plant-derived phenolics with proven antioxidant potentials has been recognized as an important strategy in both glycaemic control and the management/treatment of diabetic complications such as retinopathy [7]

Methods

Results

Conclusion