Appraisal of Pancreatic Lipase Inhibitory Potential of Ziziphus oenoplia (L.)Mill. Leaves by In Vitro and In Silico Approaches.

Pancreatic lipase is one of the crucial lipolytic enzymes of the gut that actively facilitates the digestion and absorption of the dietary triglycerides and cholesteryl esters. Although it has been deemed as one of the most reliable targets for the treatment of obesity and/or dyslipidemia, to date, orlistat is the only known FDA-approved, effective, oral pancreatic lipase inhibitor available for clinical use apart from the centrally acting antiobesity agents. However, it is known to be associated with adverse gastrointestinal and renal complications. In this study, we attempted to assess the antioxidant and porcine pancreatic lipase inhibitory potentials of Ziziphus oenoplia (L.)Mill. leaves through a systematic combination of in vitro and in silico approaches. Among the four different extracts including petroleum ether extract, ethyl acetate extract, ethanolic extract, and aqueous extract obtained through successive solvent extraction, the ethyl acetate extract has outperformed the other extracts and orderly displayed competent peroxide scavenging (IC50 value: 267.30 µg/mL) and porcine pancreatic lipase inhibitory (IC50 value: 444.44 µg/mL) potentials compared to the selected reference compounds: ascorbic acid (IC50 value: 251.50 µg/mL) and orlistat (IC50 value: 502.51 µg/mL) in the selected in vitro assay models. In addition, based on the molecular docking simulations of the six essential phytoconstituents of the leaves of Ziziphus oenoplia (L.)Mill. and their respective chemical analogues against the crystal structure of pancreatic lipase-colipase complex (PDB ID: 1LPB), four best-ranked molecules (PubChem CIDs: 15515703, 132582306, 11260294, and 44440845) have been proposed. Further, among these, the interaction potentials of the two top-ranked molecules (PubChem CIDs: 132582306 and 15515703) were analyzed through molecular dynamics (MD) simulations at a trajectory of 100 ns. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were theoretically predicted for all of the molecules using Swiss ADME and ADMET lab2.0. In conclusion, Ziziphus oenoplia (L.)Mill. leaves could become a prominent source for various potent bioactive compounds that may serve as prospective leads for the development of clinically cognizable pancreatic lipase inhibitors, provided their pharmacokinetic and in particular toxicity properties are thoroughly optimized.

Anti-cancer peptides: their current trends in the development of peptide-based therapy and anti-tumor drugs.

Human cancer remains a cause of high mortality throughout the world. The conventional methods and therapies currently employed for treatment are followed by moderate-to-severe side effects. They have not generated curative results due to the ineffectiveness of treatments. Besides, the associated high costs, technical requirements, and cytotoxicity further characterize their limitations. Due to relatively higher presidencies, bioactive peptides with anti-cancer attributes have recently become treatment choices within the therapeutic arsenal. The peptides act as potential anti-cancer agents explicitly targeting tumor cells while being less toxic to normal cells. The anti-cancer peptides are isolated from various natural sources, exhibit high selectivity and high penetration efficiency, and could be quickly restructured. The therapeutic benefits of compatible anti-cancer peptides have contributed to the significant expansion of cancer treatment; albeit, the mechanisms by which bioactive peptides inhibit the proliferation of tumor cells remain unclear. This review will provide a framework for assessing anti-cancer peptides' structural and functional aspects. It shall provide appropriate information on their mode of action to support and strengthen efforts to improve cancer prevention. The article will mention the therapeutic health benefits of anti-cancer peptides. Their importance in clinical studies is elaborated for reducing cancer incidences and developing sustainable treatment models.

Therapeutic Implications of Superoxide Dismutase And Its Importance in Kinase Drug Discovery.

In recent years, several scientific investigations have reported the therapeutic implications of superoxide dismutase (SOD) against oxidative stress and -induced pathology in clinical and preclinical trials. Indeed, various kinase, molecular signaling and physiological process has altered by reactive oxygen species. In spite of the abundant available literature reports, patents, clinical trials and commercialized products, the therapeutic application of SOD as a potential drug still remains unclear. Owing to the technical challenges associated with the utilization of SOD as a drug, we revisited the structural arrangement and cellular signaling, significant association with kinase, exploring the new target sites and introducing new formulation strategies such as gene modulation, nano-formulations and click chemistry is a prerequisite. In-addition to gene modulation strategies, encapsulated formulation within a nano-carrier for producing promising SOD therapeutic effects, application of click chemistry including bioconjugation and cyclo-addition are the most prominent methods to produce highly efficient SOD formulations. Thus, the present review enlightens the foremost technique which may have better interaction with kinase and other cellular signaling for regulating the physiological process.