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Background: Hyperlipidemia is a common precursor to cardiovascular diseases, necessitating effective intervention. This study explores the potential of a bioactive fraction derived from Kalanchoe pinnata leaf, a less-explored natural source, for its antihyperlipidemic properties. Objectives: The primary objectives of this research are to isolate and assess the bioactive fraction from Kalanchoe pinnata leaves extract for its antihyperlipidemic attributes using a murine model. The study also aims to characterize the fraction and investigate its interactions with hyperlipidemia-related proteins. Materials and Methods: Kalanchoe pinnata leaves were extracted and fractionated via flash chromatography. Isolated fractions underwent phytochemical, antioxidant, and enzyme inhibition assays in vitro. In vivo, selected fractions were tested in Triton WR-1339-induced hyperlipidemic mice. Fraction F2, which exhibits the most potent activity, was characterized using HPTLC MS/MSn chromatography. Molecular docking studies explored interactions between F2 compounds and hyperlipidemia-related proteins. Results: Fraction F2 displayed significant in vivo antihyperlipidemic activity, with observable morphological changes in mice. HPTLC MS/MSn identified four major compounds in F2, while docking studies revealed potential interactions with hyperlipidemia-related proteins. Conclusion: This study underscores F2's potential as a potent antihyperlipidemic agent sourced from Kalanchoe pinnata leaves. The identified compounds hold promise for further research in hyperlipidemia therapy development, emphasizing the therapeutic potential of natural Kalanchoe pinnata compounds for managing hyperlipidemia and related cardiovascular conditions. [ABSTRACT FROM AUTHOR]

Background: Antibiotic resistance in bacteria mediated by New Delhi Metallo-β-lactamase (NDM) is a global threat to human health with an enormous economic burden. NDM can hydrolyze all the β-lactam core-containing antibiotics including carbapenems, which are regarded as last resort antibiotics. Materials and Methods: A library of Abyssomicins was virtually screened to identify novel non-β-lactam ring-containing inhibitors of NDM-1. Different computational approaches such as molecular modeling, virtual screening, molecular docking, molecular dynamics simulation, ADMET profiling, and free energy calculations were utilized for this purpose. Results: Virtual screening and ADMET profiling shortlisted Abyssomicin W and Neoabyssomicin B as the most promising candidate molecules. An in-depth analysis of protein-ligand interactions by molecular docking revealed that both ligands bind the active site of NDM-1. The identified inhibitors interacted with key catalytic residues as well as other residues around the active site of NDM-1. Hydrogen bonding and hydrophobic interactions played a significant role in stabilizing the protein-inhibitor complexes. The docking energy of NDM-1-Abyssomicin W, and NDM-1-Neoabyssomicin B complexes were − 9.6 kcal/mol and − 9.5 kcal/mol, respectively, which were higher than NDM-1-Methicillin (control) complex (−7.3 kcal/mol). Molecular dynamics simulation and free energy calculations by MM-PBSA also confirmed the stability of NDM-1-Abyssomicin W, and NDM-1-Neoabyssomicin B complexes. Conclusion: The findings of this study suggest that Abyssomicins serve as potential inhibitors of NDM-1. However, these results need to be validated in vitro and in vivo. This study may serve as a basis for further developing Abyssomicins as novel inhibitors of β-lactamases. [ABSTRACT FROM AUTHOR]