ABSTRACT
Medicinal plants have been used in the past for the treatment of diseases and continue to be an important reservoirfor the development of new drugs. With the increasing burden of cancer globally, there is a need to find neweranticancer agents. The process of identification and evaluation of cytotoxic molecules from plants can be achievedconveniently by using simple yet reliable screening models and combining with in silico techniques. Pachygone ovata,least explored plant from Menispermaceae family, is known to be rich in alkaloids. This study aimed to identify thecytotoxic constituents from Pachygone ovata through bioactivity-guided fractionation using Brine shrimp lethalitybioassay as a screening model. The active fraction in this assay was evaluated for its in vitro cytotoxic activity onhuman tumor cell lines. Some reported alkaloids were studied for their binding affinities with topoisomerase II bymolecular docking. The study revealed the cytotoxic constituents from P. ovata. The study also revealed alkaloids withhigher binding affinity with topoisomerase II, and the scope for further use leads to the development of new drugs.
ABSTRACT
Objective: To identify alpha-glucosidase inhibitors from Ficus benghalensis and analyze gene set enrichment of regulated protein molecules. Methods: The phytoconstituents of Ficus benghalensis were queried for inhibitors of alpha-glucosidase, also identified as aldose reductase inhibitors. Druglikeness score, absorption, distribution, metabolism, excretion and toxicity profile, biological spectrum, and gene expression were predicated for each compound. Docking study was performed to predict the binding affinity with alpha-glucosidase and aldose reductase and compared with clinically proven molecules. Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed for the regulated genes to identify the modulated pathways. Results: Apigenin, 3,4',5,7-tetrahydroxy-3'-methoxyflavone, and kaempferol were identified as inhibitors of alpha-glucosidase and aldose reductase. Kaempferol was predicted to possess the highest binding affinity with both targets. The p53 signaling pathway was predicted to modulate the majority of protein molecules in diabetes mellitus. All the alpha-glucosidase inhibitors were also predicted as membrane integrity agonist and anti-mutagenic compounds. Conclusions: The current study indicates alpha-glucosidase inhibitors from Ficus benghalensis can act as aldose reductase inhibitors after absorption from the intestinal tract. Furthermore, these phytoconstituents are involved in the regulation of numerous protein molecules and pathways. Hence, the anti-diabetic efficacies of these compounds are due to their action on multiple protein molecules and synergistic effects which should be confirmed by future investigations.