In-vitro anti-diabetic activity and in-silico studies of binding energies of palmatine with alpha-amylase, alpha-glucosidase and DPP-IV enzymes

Abstract

Palmatine a protoberberine alkaloid has been previously reported to possess in vivo antidiabetic and antioxidant property. The aim of the experiment is to evaluate the in vitro antidiabetic activity and in-silico studies of the binding energies of Palmatine, acarbose, and Sitagliptin with the three enzymes of alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase-IV (DPP-IV). The in vitro antidiabetic study was done by evaluating the inhibitory effect of palmatine on the activities of alpha-amylase, alpha-glucosidase, and DPP-IV. Acarbose, and sitagliptin was used as standard drug. The molecular docking study was performed to study the binding interactions of palmatine with alpha-glucosidase, a-amylase, and DPP-IV. The binding interactions were compared with the standard compounds Sitagliptin and acarbose. Palmatine with IC50 (1.31 ± 0.27 µM) showed significant difference of (< 0.0001) higher inhibiting effect on alpha-amylase and weak inhibiting effect on alpha-glucosidase enzyme with IC50 (9.39 ± 0.27 µM) and DPP-IV with IC50 (8.7 ± 1.82 µM). Palmatine possess inhibition effect on the three enzymes.

Citrus Fruits as Source of Novel Bioactive Peptides: in-vitro and in-silico Analysis of Atheroprotective Potentials

“…Yet, the results from in-vitro antihyperglycemic assays present almost inverse trends in most dPREs. A probable explanation of this sort of differential binding preference may be found in previous studies which showed weak binding of metformin to α-glucosidase while acarbose exhibits strong affinity [45]. While not directly corresponding to all dPREs, docking of identified peptides from two selected samples along with control molecules show how the GP1BA and amylase binding cavity is dictated by large number of strong H-bonding and electro-attractive interactions more oriented towards metformin binding rather than the hydrophobic binding pocket of α-glucosidase optimized for quercetin, warfarin and hydrophobic peptide interactions.…”

Enzymatic production of 4-cholesten-3-one using cholesterol oxidase from Bacillus cereus strain KAVK5 and its potentiality toward the inhibition of disease-associated proteins an in silico approach

“…Inhibition of adipose tissue enlargement was considered as a target to control obesity disorder. This process can be regulated by transcriptional factors like sterol regulatory element-binding protein 1 (SREBP1) (Park et al, 2019). Acetyl-CoA carboxylase played a vital role in fatty acid metabolism and was designed as a potent target for developing a new therapeutic agent in controlling obesity (Gago et al, 2011).…”

“…α-Amylase, an enzyme also called endonuclease enzyme, is engaged in the digestion of polysaccharides, whereas α-glucosidase is situated in the intestinal part which participates in absorbing oligosaccharides (Telagari and Hullatti, 2015). These enzymes were treated as key enzymes that maintained blood glucose levels by slowing the digestive process and absorption of carbohydrates and incertins (Okechukwu et al, 2020). Type 2 diabetes mellitus appears more than that of the total diabetic population, which correlates with obesity-induced insulin resistance and subsequently secreted insulin from the β-cells of the pancreas.…”

“…In modern drug discovery, a molecular docking method proves the action of small molecules in the binding site of a target protein. This protein-ligand or protein-protein docking plays a crucial role in predicting the orientation of the ligand where it binds to the receptor (Pagadala et al, 2017). ArgusLab is a new molecular modeling package used for molecular docking study.…”

Roles of Alkaloids from Medicinal Plants in the Management of Diabetes Mellitus

“…A protoberberine alkaloid, palmatine, inhibits α-amylase and α-glucosidase activities with an IC 50 of 1.31 ± 0.27 and 9.39 ± 0.27 µM, respectively [29]. Oriciacridone C, 1,3,5trihydroxy-4-(c,c-dimethylallyl)-acridone, and oriciacridone F (Figure 3) from the stem bark of Oriciopsis glaberrima showed an α-glucosidase inhibitory activity (56 ± 5.4, 17 ± 1.0, and 34.05 ± 17 mM) [30].…”