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OBJECTIVE@#Duranta repens is reported to contain a wide array of secondary metabolites, including α-amylase and α-glucosidase inhibitors, and - has potent antioxidant activity. The present study evaluated the network pharmacology of D. repens (whole plant) with targets related to diabetes mellitus and assessed its outcome by evaluating the effects of the hydroalcoholic extract of D. repens in streptozotocin-nicotinamide-induced diabetes mellitus in rats.@*METHODS@#Phytoconstituents of D. repens were retrieved from an open-source database and published literature, and their targets were predicted for diabetes mellitus using BindingDB and the therapeutic target database. Protein-protein interaction was predicted using STRING, and pathways involved in diabetes mellitus were identified using the Kyoto Encyclopedia of Genes and Genomes pathway browser. Druglikeness, ADMET profile (absorption, distribution, metabolism, excretion and toxicity) and cytotoxicity of compounds modulating proteins involved in diabetes were predicted using MolSoft, admetSAR2.0 and CLC-Pred, respectively. The interaction network among phytoconstituents, proteins and pathways was constructed using Cytoscape, and the docking study was performed using AutoDock4.0. The hydroalcoholic extract of D. repens was evaluated using streptozotocin-nicotinamide-induced diabetes mellitus animal model for 28 d, followed by an oral glucose tolerance test. At the end of the study, biochemical parameters like glycogen content, hepatic enzymes, antioxidant biomarkers and lipid profiles were quantified. Further, the liver and pancreas were collected for a histopathology study.@*RESULTS@#Thirty-six different secondary metabolites from D. repens were identified to regulate thirty-one targets involved in diabetes mellitus, in which protein-tyrosine phosphatase 1B (PTP1B) was primarily targeted. Enrichment analysis of modulated proteins identified 12 different pathways in diabetic pathogenesis in which the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway was chiefly regulated. The docking study found that durantanin I possessed the highest binding affinity (-8.9 kcal/mol) with PTP1B. Similarly, ADMET profiling showed that the majority of bioactive constituents from D. repens had higher human intestinal absorptivity and minimal cytotoxicity to normal cell lines, than tumor cell lines. Further, an in vivo animal study reflected the efficacy of the hydroalcoholic extract of D. repens to lower the elevated blood glucose level by stimulating insulin secretion, maintaining pancreatic β cell mass, regulating glycolysis/gluconeogenesis and enhancing the glucose uptake in skeletal muscles.@*CONCLUSION@#The present study reflected the probable network interaction of bioactive constituents from D. repens, their targets and modulated pathways, which identified the prime regulation of the PI3K-Akt signaling pathway and PTP1B protein. Modulation of PTP1B protein and PI3K-Akt signaling pathway could contribute to enhancing glucose uptake, insulin production and glycolysis and decreasing gluconeogenesis in diabetes, which was evaluated via the experimental study.
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Objective: To report in vitro anti-oxidant activity and cytotoxicity of hydroalcoholic extract of Ficus benghalensis (bark) and Duranta repens (whole plant), and present the probable biological spectrum of major anti-oxidants from both plants. Methods: The coarse powder of both plants was first extracted with 70% ethanol (maceration) followed by 99% ethanol (Soxhlet-extraction). Anti-oxidant activity of the extracts was evaluated using DPPH, H2O2, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS), NO scavenging assay, total antioxidant capacity, cupric reducing antioxidant capacity (CUPRAC), and metal chelating assay. Cytotoxicity of both extracts was evaluated using MTT assay in both tumor and normal cell lines i.e. Chinese hamster ovary cells (CHO) and A549 cells. Biological activity of individual anti-oxidants from both medicinal plants was identified using prediction of activity spectra for substances and a docking study was performed by using autodock4.0. Results: Hydroalcoholic extract of F. benghalensis and D. repens showed the highest free radical scavenging (ABTS) and chelating capacity respectively. Both extracts showed minimum cytotoxicity in normal cell lines compared to tumor cell lines. Computer imitation hits reflected the multiple biological activities agreeing with the folk use and some scientific reports. Further, we found the binding affinity of predicted anti-oxidant compounds with multiple protein molecules involved in oxidative stress. Conclusion: The present study reports the probable anti-oxidant mechanism for two folk agents and also presents probable pharmacological activities via computer simulations.
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The crude ethanol extracts (stem and fruits), their fractions and two triterpenes, beta-Amyrin and 12-Oleanene 3beta, 21beta-diol, isolated as a mixture from the chloroform soluble fraction of an ethanolic extract of Duranta repens stem, were evaluated for antibacterial, antifungal activities by the disc diffusion method and cytotoxicity by brine shrimp lethality bioassay. The structures of the two compounds were confirmed by IR, 1H-NMR, 13C-NMR and LC-MS spectral data. The chloroform soluble fraction of stem and ethanol extract of fruits possess potent antishigellosis activity and also exhibited moderate activity against some pathogenic bacteria and fungi but the isolated compound 1 (mixture of beta-Amyrin and 12-Oleanene 3beta, 21beta-diol) showed mild to moderate inhibitory activity to microbial growth. The minimum inhibitory concentrations (MICs) of the extracts (stem and fruits), their fractions and compound 1 were found to be in the range of 32~128 microg/ml. The chloroform soluble fractions of stem and ethanol extract of fruit showed significant cytotoxicity with LC50 value of 0.94 microg/ml and 0.49 microg/ml, respectively against brine shrimp larvae.