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Zanthoxylum rhetsa (ZR) is used traditionally to manage a variety of ailments, including diabetes. Oxidative stress may accelerate the diabetic condition. The available antidiabetic and antioxidant drugs have many shortcomings including resistance, inefficiency, higher dose, side effects and costs. The goal of the current investigation was to assess the antioxidant capacity and antidiabetic activity of an ethanolic extract of Zanthoxylum rhetsa root bark (ZRRB) through in vitro, in vivo, and in silico methods. The antioxidant capacity of the ZRRB extract was measured using both the DPPH radical assay and the total antioxidant activity test. The oral glucose tolerance test (OGTT) and alloxan-induced diabetic mice model were also used to examine in vivo antidiabetic efficacy. Phytochemicals identification was done by GCMS analysis. Additionally, computational methods such as molecular docking, ADMET analysis, and molecular dynamics (MD) modeling were performed to determine the above pharmacological effects. The extract demonstrated significant DPPH scavenging activity (IC50 = 42.65 μg/mL). In the OGTT test and alloxan-induced diabetes mice model, the extract effectively lowered blood glucose levels. Furthermore, in vitro inhibition of pancreatic α-amylase studies demonstrated the ZRRB extract as a good antidiabetic crude drug (IC50 = 81.45 μg/mL). GCMS investigation confirmed that the crude extract contains 16 major phytoconstituents, which were docked with human peroxiredoxin-5, α-amylase, and sulfonylurea receptor 1. Docking and pharmacokinetic studies demonstrated that among 16 phytoconstituents, 6H-indolo[3,2,1-de] [1,5]naphthyridin-6-one (CID: 97176) showed the highest binding affinity to targeted enzymes, and imitated Lipinski's rule of five. Furthermore, MD simulation data confirmed that the aforementioned compound is very steady to the binding site of α-amylase and sulfonylurea receptor 1 receptors. Findings from in vitro, in vivo and in silico investigation suggest that ZRRB extract contains a lead compound that could be a potent source of antidiabetic drug candidate. [ABSTRACT FROM AUTHOR]

Present study was undertaken to evaluate the anti-allergic activity of the ethanolic bark extract of Amoora cucullata (EBAC) in mice followed by molecular docking analysis and also to quantify the major bioactive polyphenolic constituents by HPLC analysis. Anti-allergic activity was evaluated using Toluene-2,4-diisocyanate (TDI)-sensitized allergy model mice by determining nasal allergy-like symptoms as well as counting the total and differential leukocytes profile of blood and Broncho Alveolar Lavage (BAL) fluid. In silico molecular docking study was performed using Schrödinger Maestro 10.1 on eight isolated compounds against Histamine Methyltransferase receptor in order to justify the anti-allergic activity of the extract. Acute toxicity test was performed to determine the safety of the extract. HPLC analysis exhibited the presence of 3,4-dihydroxy benzoic acid, catechol, (-) epicatechin, caffeic acid, syringic acid, rutin hydrate and trans-cinnamic acid. In anti-allergic activity test, oral administration of the EBAC improved nasal-allergic symptoms of TDI-induced allergic rhinitis in experimental mice. There was also a conspicuous decrease in the number of leukocytes, neutrophils, lymphocytes, eosinophils, monocytes and basophils in both blood and Broncho Alveolar Lavage (BAL) fluid of the mice treated with EBAC as compared to TDI-sensitized mice. Among the identified compounds from this plant, the docking score of Chrysin, Apigenin, Kaempferol-3-O-beta-D-glucopyranoside, and Stigmasterol against Histamine Methyltransferase receptor were comparable with that of standard drug Cetirizine (-9.519 kcal/mol). The EBAC did not exhibit any mortality in mice even at 3 gm/kg dose. The results of this study confirm the antiallergic activity of the plant in both in vivo and in silico investigations. [ABSTRACT FROM AUTHOR]