Multiprotein Inhibitory Effect of Dietary Polyphenol Rutin from Whole Green Jackfruit Flour Targeting Different Stages of Diabetes Mellitus: Defining a Bio-Computational Stratagem

Abstract

The anti-diabetic potential of whole unripe jackfruit (peel with pulp, flake, and seed) was investigated using inhibitory assays for α-glucosidase, α-amylase, aldose reductase, and glycation at multiple stages. Using activity-guided repeated fractionation on a silica gel column chromatography, dietary flavonoid rutin with potent antihyperglycemic activity was extracted from the methanol extract of whole jackfruit flour (MJ). Rutin was found to inhibit both α-glucosidase (IC50: 7.86 µg/mL) and α-amylase (IC50: 22.00 µg/mL) in a competitive manner of inhibition with low Ki values. In addition, in vitro glycation experiments revealed that rutin prevented each stage of protein glycation as well as the production of intermediate molecules. Furthermore, rutin significantly inhibited aldose reductase (IC50: 2.75 µg/mL) in a non-competitive manner. During in silico studies, molecular docking and molecular dynamics simulation studies have suggested that rutin has a high binding affinity for the enzymes studied, which could explain its inhibitory effects. Rutin interacted with the key residues of the target enzymes’ inhibitor binding sites. Compared to the controls used, rutin had a higher binding efficiency as well as stability in the inhibitor binding pocket of the target enzymes. According to our findings, the presence of rutin is more likely to be associated with the potential of MJ in antihyperglycemic activity via inhibition of α-glucosidase and in anti-diabetic action via inhibition of the polyol pathway and protein glycation. The bio-computational study indicates rutin as a potential lead inhibitor of all the target enzymes used and could be used as an effective anti-diabetic drug in the near future.

Synthesis of Pyrazoline‐Embedded 1,2,3‐Triazole Derivatives via 1,3‐Dipolar Cycloaddition Reactions with in vitro and in silico Studies

“…The usage of appropriate control drugs is important to compare and attribute any biological activity (in this case, multiple enzyme inhibition) with the compounds 5 a – 5 l . As a positive control, acarbose (for both α‐amylase and α‐glucosidase) was employed [40,41] …”

“…The IC 50 values signify the concentrations of test samples that can 50 % inhibit the activity of an enzyme as compared to the control. [40,41] The In vitro studies revealed that compounds had effective α-glucosidase inhibitory potential than α-amylase enzyme. The In vitro α-glucosidase inhibitory studies revealed that 5 k had effective inhibitory potential than other samples tested.…”

“…The usage of appropriate control drugs is important to compare and attribute any biological activity (in this case, multiple enzyme inhibition) with the compounds 5 a-5 l. As a positive control, acarbose (for both α-amylase and αglucosidase) was employed. [40,41] The α-amylase (EC 3.2.1.1, categorized as type-VI B porcine pancreatic α-amylase) inhibition was assayed. [40] In the assay, soluble starch (1 %) was used as a substrate in a 0.02 M sodium phosphate buffer (pH 6.9 with 0.006 M NaCl).…”

Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus

“…Different food products including milk, vegetables, and fruits have got anti-hyperlipidemic and anti-diabetic factors [ 14 ]. In the current scenario, the usage of phytochemical products for the treatment of anti-diabetic conditions has been trending, since they are associated with a low risk of developing adverse effects.…”

“…Many of the Artocarpus species are potentially used for both medicines as well as timber in the Asian subcontinent. The most popular of the species is Artocarpus heterophyllus (jackfruit) belongs to the Moraceae family and is a common household tree in India and Bangladesh [ 14 ]. Considering its economic value and abundance, several studies have been carried out on jackfruit suggesting that it possesses diverse medicinal uses including antioxidant, anti-inflammatory, antimicrobial, anticarcinogenic, antifungal, antineoplastic, and hypoglycemic effects inhibiting melanin biosynthesis and wound healing properties [ 15 ].…”