ABSTRACT
Diabetes mellitus is a typical life threatening of disease, which generate due to the dysfunction of ß cells of pancreas. In 2014, WHO stated that 422â million people were infected with DM. The current pattern of management of diabetes included synthetic or plant based oral hypoglycemic drugs and insulin but drug resentence is become a very big issues in antidiabetic therapy. Thus, it's very earnest to discover now medication for this disease. Now the days, it is well acknowledged that diabetic patients are more prone towards covid and related complications. Thus, medical practitioners reformed the methodology of prescribing medication for covid infected antidiabetic therapy and encouraging the medication contains dual pharmacological properties. It is also well know that polyphenols specifically hold a significant role in oxidative stress and reduced the severity of many inflammatory diseases. Cucumis melo has rich history as ethano-pharmacological use in Indian subcontinent. The fruit and seed are well-known for the treatment of various diseases due to the presence of phenolics. Therefore, in this study, the combined mixture of flower and seeds were used for the extraction of polyphenolic rich extract and tested for antidiabetic activity through the antioxidant and inâ vivo experiments. The antioxidant potential measurement exhibited that the selected plant extract has the significant competence to down-regulate oxidative stress (DPPH scavenging IC50 at 60.7±1.05â µg/mL, ABTS IC50 at 62.15±0.50â µg/mL). Furthermore, the major polyphenolic phyto-compounds derived from the Cucumis melo were used for inâ silico anticovid activity, docking, and complementarity studies. The anticovid activity prognosis reflected that selected phyto-compounds amentoflavone and vanillic acid have optimal possibility to interact with 3C-like protease and through this moderate anticovid activity can be exhibit. The docking experiments established that the selected compounds have propensity to interact with protein tyrosine phosphatase 1B, 11ß-Hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, and catalase ß-glucuronidase receptor. Inâ vivo experiments showed that 500â mg/kg, Cucumis melo extract ominously amplified body weight, plasma insulin, high-density lipoprotein levels, and biochemical markers. Furthermore, extract significantly downregulate the blood glucose, total cholesterol, triglycerides, low-density lipoprotein, and very low-density lipoprotein.
Subject(s)
COVID-19 , Cucumis melo , Diabetes Mellitus, Experimental , Momordica , 11-beta-Hydroxysteroid Dehydrogenases , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Biomarkers , Blood Glucose , Catalase/metabolism , Cholesterol , Cucumis melo/metabolism , Diabetes Mellitus, Experimental/metabolism , Glucuronidase , Glutathione Peroxidase/metabolism , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Insulin , Lipoproteins, HDL/therapeutic use , Lipoproteins, LDL/therapeutic use , Momordica/metabolism , Peptide Hydrolases , Plant Extracts/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Superoxide Dismutase/metabolism , Triglycerides , Vanillic AcidABSTRACT
A respiratory pandemic known as coronavirus disease-19 (COVID-19) has created havoc since it emerged from Wuhan, China. COVID-19 is caused by a newly emerged SARS coronavirus (SARS-CoV) with increased pathogenicity named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the lack of understanding of the mechanism of pathogenesis, an effective therapeutic option is unavailable. Epidemics described in Unani ancient literature include nazla-e-wabai and humma-e-wabai, and most of the symptoms of COVID-19 resemble nazla-e-wabai. Hence, in light of Unani literature, the treatment of COVID-19 can be managed with the composites prescribed in Unani medicine for nazla-e-wabai. In this study, a structure-based drug design approach was carried out to check the effectiveness of the pharmacologically active constituents of the Unani composites prescribed to treat nazla-e-wabai against SARS-CoV-2. We performed molecular docking of the active constituents of these composites against the main protease (Mpro), a potential drug target in SARS-CoV-2. Using detailed molecular docking analysis, Habb-ul-aas and Tabasheer were identified as potential inhibitors of SARS-CoV-2 Mpro. The active constituents of both these composites bind to the substrate-binding pocket of SARS-CoV-2 Mpro, forming interactions with key residues of the binding pocket. Molecular dynamics (MD) simulation suggested the binding of active constituents of Habb-ul-aas with SARS-CoV-2 Mpro with a strong affinity as compared to the constituents of Tabasheer. Thus, this study sheds light on the use of these Unani composites in COVID-19 therapeutics.Communicated by Ramaswamy H. Sarma.
Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Coronavirus 3C Proteases , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Peptide Hydrolases/metabolism , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Viral Nonstructural Proteins/chemistryABSTRACT
Plant extracts continue gaining significant prominence in green synthesis of silver nanoparticles (AgNPs), due to their potential applications in nano-medicine and material engineering. This work reports on green synthesis of silver nanoparticles (AgNPs) from aqueous extracts of Iboza Riparia leaf and Ilex Mitis root bark with diterpenes (DTPs) and saponins (SPNs) as major components. After TEM, DLS, TGA/DSC, ATR, XRD and UV-Vis characterization, the relevant cytotoxicity studies were conducted with the MTT assay on human embryonic kidney cells (HEK293T) followed by antioxidant activity with ABTS. Overall, the AgNPs-DTPs (156nm) were found to be less toxic with 49.7% cell viability, while AgNPs-SPNs (50nm) and AgNPs-PVA (44nm) had cell viability of 40.8 and 28.0% respectively at 400µM. Based on the cytotoxicity and antioxidant activity, it is fair to report that these plant extracts have potential reducing and capping agents as they retain chemical properties on the surface of the nanoparticles.