Computational Analysis for Physicochemical Properties of Compounds in Senna auriculata Leaves Methanolic Extract to have Antidiabetic Potentials and their Molecular Interaction with α-amylase

Abdulaziz Bin Dukhyil

doi:10.9734/jpri/2021/v33i54a33716

Abstract

Aims: Diabetes mellitus (DM) is chronic disorder well known for increased glucose level in blood. This disease can be controlled by inhibiting the enzyme (e.g., α-amylase) involve in carbohydrate hydrolysis. Senna auriculata leaves methanolic extract (SALME) have potential antidiabetic properties and it was also found to be safe in preclinical studies. In this study the aim was to explore the molecular interactions of α-amylase and bioactive compounds in SALME and their physicochemical properties. Methodology: Computational approach such as molecular docking and physicochemical analysis prediction was applied to understand the antidiabetic potential of natural compounds present in SALME. Results: The results showed from physicochemical analysis that out of 11 only 7 compounds are having drug like properties which are orally and intestinally better bioavailable. Furthermore, molecular docking analysis explained that three compounds (C3, C4, and C7) have lower binding energy, ΔG (-8, -9.1, -9.5 kcal/mol) and better binding affinity, Ki (7.31 x 105, 4.68 x 106, and 9.2 x 106 M-1, respectively) than the acarbose ΔG (-7.8 kcal/mol) and Ki (6.18 x 105 M-1), a well-known FDA approved medication for DM. The study also explained the binding pattern that the catalytic residue such as Asp197, Glu233 and Asp300 are involved in stabilizing the natural compounds with in the catalytic active site of target enzyme. Conclusions: From the results it has been concluded that these three compounds found in SALME have better inhibitory potential for α-amylase in comparison with acarbose. Further validation of the findings is required through molecular dynamics simulation, ADME-T study, and in-vitro enzyme inhibition by the purified compounds.

Highlights

Diabetes is a non-communicable chronic disorder which effects nearly 422 million people globally, responsible for 1.5 million deaths annually and predicted to negatively affect around 700 million people in 2045 [1,2]
Type 2 Diabetes mellitus (T2DM) occurs due to imbalance in carbohydrate metabolism which decreases the cellular concentration of glucose and negatively effects several other metabolic processes related to nephropathy, retinopathy, heart, fracture, Covid-19, neuro-disorder [3,4,5,6,7]
The common causes for T2DM are defects in insulin secretion destruction of beta cell in pancreas, insulin deficiency, and/or nonresponsive insulin receptors which leave the high level of glucose in blood and is the primary diagnostic parameter for hyperglycemia [8]

Summary

Introduction

Diabetes is a non-communicable chronic disorder which effects nearly 422 million people globally, responsible for 1.5 million deaths annually and predicted to negatively affect around 700 million people in 2045 [1,2]. Type 2 Diabetes mellitus (T2DM) occurs due to imbalance in carbohydrate metabolism which decreases the cellular concentration of glucose and negatively effects several other metabolic processes related to nephropathy, retinopathy, heart, fracture, Covid-19, neuro-disorder [3,4,5,6,7]. There is an increased economic burden of diabetes management and presumed to reach up to USD 2.5 million in 2030, which indicates an urgent need of cost-effective management and control of T2DM [9]. Several therapeutic medications for the management of T2DM are well-proven αamylase inhibitors such as acarbose, miglitol and voglibose [14]. These medications have several side effects like diarrhea, gastrointestinal discomfort, hepatotoxicity, and pancreatitis [15]. Efforts made to develop novel inhibitors, of natural origin to minimize the side effects and economic burden [16,17]

Methods

Results

Conclusion