Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools.

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL-1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.

Two new 5(14)-membered type cyclopeptide alkaloids from root bark of Ziziphus spina-christi (L.) Desf.

Six 5(14)-membered ring type of cyclopeptide alkaloids (CPAs), including two undescribed members, 1-hydro,2ß-methoxy-mauritine-A (1) and 1-hydro,2α-methoxy-mauritine-A (2), together with four known compounds, mauritine-A (3), mauritine C (4), amphibine-A (5), and amphibine-E (6), were isolated from the root bark of Ziziphus spina-christi (L.) Desf., Their structures were determined by multiple spectral analyses, including UV, IR, 1D NMR, 2D NMR, EI-MS, HR-EI-MS, FAB-MS and ESI-MS, and by comparison with literature. All six CPAs were tested in vitro for cytotoxicity by three human cancer cell lines (MCF7, H460 and Hela) and a human normal cell line (BJ). None of the compounds showed cytotoxicity towards all tested cell lines.

Discovery of potential HER2 inhibitors from Mangifera indica for the treatment of HER2-Positive breast cancer: an integrated computational approach.

Human epidermal growth factor receptor 2 (HER2) is a member of epidermal growth factor receptors with tyrosine kinase functionality. The dimerization of HER2 leads to the autophosphorylation of tyrosine residues within its cytoplasmic domain, resulting in hyperactivation of several downstream signal transduction pathways that play an important role in tumorigenesis, cancer aggressiveness and cell proliferation. Amplification or overexpression of HER2 has been found in approximately 15-30% of breast cancers. Hence, HER2 serve as a therapeutic biomarker in breast cancer. Herein, we applied structural bioinformatics techniques via molecular docking, molecular dynamics simulations, Molecular mechanics/generalized Born surface area (MM/GBSA) calculations and pharmacokinetic models to identify putative HER2 inhibitors. Application of stringent molecular docking results in the identification of bioactive compounds from Mangifera indica as selective, potent inhibitors of HER2. However, only the top three compounds with the highest negative docking score (< -9kcal/mol) was considered in reference to neratinib (-8.601 kcal/mol) for computational analysis. The molecular dynamics simulations and post-simulation analysis of docked HER2-ligand complexes unveil the substantial stability for M. indica ligands over the 100 ns simulation period. Additionally, MM/GBSA binding free energy calculation supports the inhibitory potential for the docked ligands, which exclusively revealed the highest binding energy for selected M. indica ligands than the reference compound (neratinib). The pharmacokinetic model showed that M. indica ligands are promising therapeutic agents. Conclusively, bioactive compounds from M. indica may serve as lead molecules that could be developed into potent and effective HER2 inhibitors for breast cancer treatment.Communicated by Ramaswamy H. Sarma.

Identification of Terpenoids From Abrus precatorius Against Parkinson's Disease Proteins Using In Silico Approach.

Parkinson's disease (PD) is the second major neuro-degenrative disorder that causes morbidity and mortality among older populations. Terpenoids were reported as potential neuro-protective agents. Therefore, this study seeks to unlock the inhibitory potential of terpenoids from Abrus precatorius seeds against proteins involve in PD pathogenesis. In this study, in silico molecular docking of 5 terpenoids derived from high-performance liquid chromatography (HPLC) analysis of A. precatorius seeds against α-synuclein, catechol-o-methyltransferase, and monoamine oxidase B which are markers of PD was performed using Autodock vina. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) of the hits were done using Swiss ADME predictor and molecular dynamic (MD) simulation of the hit-protein complex was performed using Desmond Schrodinger software. Five out of 6 compounds satisfied the ADME/Tox parameters and showed varying degrees of binding affinities with selected proteins. Drimenin-α-synuclein complex showed the lowest binding energy of -9.1 kcal/mol followed by interaction with key amino acid residues necessary for α-synuclein inhibition. The selection of this complex was justified by its stability in MD simulation conducted for 10 ns and exhibited stable interaction in terms of root mean square deviation (RMSD) and root mean square deviation error fluctuation (RMSF) values.

Effect of Curculigo pilosa supplemented diet on blood sugar, lipid metabolism, hepatic oxidative stress and carbohydrate metabolism enzymes in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus (DM) has continued to raise concern globally and Curculigo pilosa (CP) is used for its treatment and management in folkloric medicine. In this study, the in vitro antioxidant abilities of CP and the effects of CP-supplemented diets on blood sugar, lipid metabolism, oxidative stress and key carbohydrate metabolizing enzymes in streptozotocin (STZ)-induced diabetic rats were investigated. METHODS: Polyphenol contents (total phenolic and total flavonoid) and antioxidant ability of different extracts of CP were determined in vitro. Diabetes mellitus were stimulated in healthy rats by single intraperitoneal administration of 50 mg/kg streptozotocin and it was confirmed by elevated blood glucose level after 3 days. Thirty six rats were distributed into six groups of six rats each and diabetic rats were fed with 5 and 10% CP-supplemented diet for 21 days. Thereafter, the effects of the dietary regimen were evaluated on blood glucose, body weight, hepatic carbohydrate metabolizing enzymes, lipid profile, oxidative stress markers, serum markers of hepatic and renal damages and histopathology studies. RESULTS: Different extracts of CP contained polyphenol contents and exhibited antioxidant properties in different models used. Diabetic rats showed elevated level of blood glucose and body weight loss. Treatment of diabetic rats with CP-supplemented diet significantly (p < 0.05) lowered the blood glucose and improved body weight loss. Also, the treatment with the CP-supplemented diet significantly (p < 0.05) enhanced the activities of hepatic glycolytic (hexokinase and glucose-6-dehydrogenase) and lowered the gluconeogenic (fructose 1, 6 biphosphatase and glucose-6-phosphatase) enzymes in diabetic rats. The lipid profile, oxidative stress markers and serum markers of hepatic and renal damages were significantly (p < 0.05) restored to near normalcy in the diabetic rats. Histopathological slides also showed improvements in pancreas and hepatic tissues of diabetic rats treated with CP-supplemented diet. CONCLUSION: Data obtained in this study suggested that CP-supplemented diet could be used as dietary regimen in the management of DM.