Identification of phytocompounds as potent inhibitors of sodium/glucose cotransporter-2 leading to diabetes treatment.

Type-II diabetes, a major metabolic disorder has threatened the very existence of a healthy life since long ago. Commercially available antidiabetic drugs are known for several adverse effects. The present study attempted to identify potential phytocompounds as inhibitors of sodium/glucose cotransporter-2 (SGLT2), a major protein that helps in glucose re-absorption from renal tubules. A total of 28 phytocompounds were collected based on the literature survey. 3D co-ordinates of phytocompounds were collected from PubChem database. Molecular docking was carried out with SGLT2 protein and the best 3 docking complexes were subjected to molecular dynamics simulation for 100 ns. Free energy changes were also analyzed using MM/PBSA analysis. Phytocompounds were also analyzed for their drug-likeness and ADMET properties. Docking study observed a strong binding affinity of phytocompounds (> -7.0 kcal/mol). More than 10 phytocompounds showed better binding affinity compared to reference drugs. Further analysis of three best docking complexes when analyzed by MD simulation showed better stability and compactness of the complexes compared to reference drug, empagliflozin. MM/PBSA analysis also revealed that van der Waals force and electrostatic energy are the major binding energy involved in the complex formation. Like docking energy, free energy analysis also observed stronger binding energies (ΔGGAS) in SGLT2-phytocompound complexes compared to empagliflozin complex. All the phytocompounds showed drug-likeness and considerable ADMET properties. The study, therefore, suggests that Trifolirhizin-6'-monoacetate, Aspalathin, and Quercetin-3-glucoside could be a possible inhibitor of SGLT2 protein. However, further studies need to be carried out to reveal the exact mode of activity.Communicated by Ramaswamy H. Sarma.

Identification of Major Compounds and α-Amylase and α-Glucosidase Inhibitory Activity of Rhizome of Musa balbisiana Colla: An in-vitro and in-silico Study.

BACKGROUND: α-Amylase and α-glucosidase inhibitors are widely used to suppress postprandial glycemia in the treatment of type-2 diabetes. OBJECTIVES: To evaluate the metallic content, phytocompounds, and α-amylase and α-glucosidase inhibitory activity of Musa balbisiana rhizome using in-vitro and in-silico methods. MATERIALS AND METHODS: Heavy metal content was detected by AAS following standard protocol. Major phytochemicals of the plant were analyzed by GC-MS technique. Enzyme inhibition study was carried out by UV/VIS spectrophotometric methods. The drug-likeness and bio-availability properties of major compounds were carried out using computer-aided tools - SwissADME and ADMElab. Docking and visualization were performed in AutoDock vina and Discovery studio tools. RESULTS: The study found that the fruits of M. balbisiana contain a negligible amount of toxic elements. GC-MS analysis showed five major compounds from the rhizome of M. balbisiana. Invitro enzyme assays revealed strong α-amylase and α-glucosidase inhibitory properties of the plant. All five compounds were predicted to have a drug-likeness property with high cell membrane permeability and bio-availability. The compounds were also predicted to have low to moderate toxicity properties. The Docking study showed strong binding affinities of plant compounds with α-amylase and α-glucosidase. Out of five compounds, C5 showed the best binding affinity with active pockets of α-amylase and α-glucosidase. CONCLUSION: The in-vitro and in-silico study suggests the antihyperglycemic property of the rhizome of Musa balbisiana and a possible candidate for the therapeutic antidiabetic agent(s).

Antioxidant and Antiproliferative Activity of Selected Medicinal Plants of Lower Assam, India: An In Vitro and In Silico Study.

BACKGROUND: The use of medicinal plants for general wellbeing and disease treatment is a common practice among tribal communities of Kokrajhar districts of Assam. However, little works have been done to study the pharmacological aspect of the plants. OBJECTIVES: The present study intends to study the antioxidant and antiproliferative properties of selected medicinal plants used by the tribal communities of the Kokrajhar district of Assam since ancient times. METHODS: Five traditionally important medicinal plants, namely, Cassia fistula, Citrus grandis, Lindernia crustacea, Sacciolepis myosuroides, and Zingiber zerumbet were investigated for antioxidant, antiproliferative (cytotoxic) and apoptosis-inducing potential in the malignant cancer cell line. Phytochemical content, such as phenolic and flavonoid content, were estimated following standard protocol. The methanolic extract of plants was investigated following the phosphomolybdate method (TAC), FRAP, DPPH, ABTS, and TBARS assays. Antiproliferative activities of the plants were carried out by MTT assay in DL and PBMC cells. The apoptotic study was carried out following the acridine orange and ethidium bromide staining method and fluorescent microscopic imaging. Based on the significant (P≤0.05) high apoptotic inducing potential of the plant and to further dissect the molecular mode of action, including downstream biological action, major phytochemicals derived from L. crustacea were investigated for its prospective binding affinity with anti-apoptotic cancer target proteins. RESULTS: Antioxidant studies by FRAP, DPPH, ABTS, and TBARS assay revealed that all five plants contain considerable free radical scavenging activity. C. fistula showed the strongest free radical scavenging activity while the fruit peel extract of C. grandis showed poor activity. The overall antioxidant activities of plants such as TAC, FRAP, DPPH, ABTS, and TBARS may be arranged in decreasing activity as C. fistula > Z. zerumbet > L. crustacea > S. myosuroides > C. grandis. MTT based cell proliferation study showed that all the plants extract significantly (P≤0.05) inhibited cell viability with negligible cytotoxicity (~5-12%) in normal cells. Moreover, L. crustacea showed promising antiproliferative and apoptosis-inducing ability against Dalton's lymphoma. It is worth mentioning that the major bioactive compounds of the most potent plant extract, L. crustacea interacted with anti-apoptotic proteins (cancer target) with higher affinity and the results are compared with reference inhibitors. CONCLUSION: It is worth noting that these plants have the potential to consider for further scientific studies in different cell lines and animal models. Furthermore, isolation and characterization of bioactive compound(s) may promise the discovery of new and valuable drugs candidate to tackle various human diseases.

Phytochemicals, antioxidant, and anthelmintic activity of selected traditional wild edible plants of lower Assam.

OBJECTIVE: Clerodendrum viscosum, Eryngium foetidum, Lippia javanica, and Murraya koenigii are one among the common wild edible plants in Northeast India which are also used as antidiabetic, stomach-ache relieving drugs, etc., The present study was aimed to reveal the phytochemical, antioxidant, and anthelmintic activity of the plants. MATERIALS AND METHODS: The antioxidant capacity of methanolic extract of plants was studied by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power, TBARS, and total antioxidant activity (TAA). Total phenolics, flavonoids, Vitamin C, carbohydrate, and protein are also estimated following standard protocols. Anthelmintic activity of the extracts has also been studied in vitro against trematode parasites. RESULTS: The result showed that the methanolic extracts of plants possess a substantial quantity of alkaloids, phenolics, flavonoids, proteins, carbohydrates, and Vitamin C. Phenolics, flavonoids, and Vitamin C contents were found higher in C. viscosum followed by M. koenigii, L. javanica, and E. foetidum. The in vitro antioxidant assays revealed substantial free radical scavenging property in all the plants. TAA increased in the order C. viscosum > M. koenigii > L. javanica > E. foetidum. Similarly, C. viscosum displayed a better antioxidant capacity with IC50 values 29.74 ± 3.63 µg and 148.77 ± 18.38 µg for DPPH and thiobarbituric acid reactive species, respectively. In addition, the plant extracts also showed good anthelmintic activity against Paramphistomum sp. Time taken for paralysis and death were 0:56 ± 0:09 h and 1:35 ± 0:07 h for L. javanica at 50 mg/mL concentration. CONCLUSION: The study therefore suggests the importance of tested plants as a natural source of free radical scavenger and plausible veterinary uses.