The synthesis and application of silver nanoparticles are increasingly becoming attractive. Hence, a critical examination of the various factors needed for the synthesis of silver nanoparticles as well as the characterization is imperative. In light of this, we addressed in this chapter, the nitty-gritty on the operational parameters (factors) and characterization relevant to synthesis of silver nanoparticle. The following characterization protocols were discussed in the context of silver nanoparticle synthesis. These protocols include spectroscopic techniques such as ultraviolet visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray fluorescence (XRF), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and X-ray photoelectron spectroscopy (XPS).
Severe SARS-CoV-2 infection causes systemic inflammation, cytokine storm and hypercytokinemia due to activation the release of pro-inflammatory cytokines that have been associated with case-fatality rate. The immune overreaction and cytokine storm in the infection caused by SARS-CoV-2 may be linked to NLRP3 inflammasome activation which has supreme importance in human innate immune response mainly against viral infections. In SARS-CoV-2 infection, NLRP3 inflammasome activation results in the stimulation and synthesis of natural killer cells (NKs), NFκB, and interferon gamma (INF-γ), while inhibiting IL-33 expression . Various efforts have identified selective inhibitors of NLRP3 inflammasome. To achieve this, studies are exploring the screening of natural compounds and/or repurposing of clinical drugs to identify potential NLRP3 inhibitors. NLRP3 inflammasome inhibitors are expected to suppress exaggerated immune reaction and cytokine storm induced-organ damage in SARS-CoV-2 infection. Therefore, NLRP3 inflammasome inhibitors could mitigate the immune-overreaction and hypercytokinemia in Covid-19 infection.
Antioxidants are compounds that inhibit the oxidation of other molecules and protect the body from the effects of free radicals, produced either by normal cell metabolism or as an effect of pollution and exposure to other external factors and are responsible for premature aging and play a role in cardiovascular disease. degenerative diseases such as cataracts, Alzheimer's disease, and cancer. While many antioxidants are found in nature, others are obtained in synthetic form and reduce oxidative stress in organisms. This review highlights the pharmacological relevance of antioxidants in fruits, plants, and other natural sources and their beneficial effect on human health through the analysis and in‐depth discussion of studies that included phytochemistry and their pharmacological effects. The information obtained for this review was collected from several scientific databases (ScienceDirect, TRIP database, PubMed/Medline, Scopus, Web of Science), professional websites, and traditional medicine books. Current pharmacological studies and evidence have shown that the various natural antioxidants present in some fruits, seeds, foods, and natural products have different health‐promoting effects. Adopting functional foods with high antioxidant potential will improve the effective and affordable management of free radical diseases while avoiding the toxicities and unwanted side effects caused by conventional medication.
Owing to the urgent need for therapeutic intervention against the SARS-coronavirus 2 (SARS-CoV-2) pandemic, we employed an in silico approach to evaluate the SARS-CoV-2 inhibitory potential of newly synthesized imidazoles. The inhibitory potential of the compounds against SARS-CoV-2 drug targets - main protease (Mpro), spike protein (Spro) and RNA-dependent RNA polymerase (RdRp) were investigated through molecular docking analysis. The binding free energy of the protein-ligand complexes were estimated, pharmacophore models were generated and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties of the compounds were determined. The compounds displayed various levels of binding affinities for the SARS-CoV-2 drug targets. Bisimidazole C2 scored highest against all the targets, with its aromatic rings including the two imidazole groups contributing to the binding. Among the phenyl-substituted 1H-imidazoles, C11 scored highest against all targets. C15 scored highest against Spro and C16 against Mpro and RdRp among the thiophene-imidazoles. The compounds interacted with HIS 41 - CYS 145 and GLU 288 – ASP 289 – GLU 290 of Mpro, ASN 501 of Spro receptor binding motif and some active site amino acids of RdRp. These novel imidazole compounds could be further developed as drug candidates against SARS-CoV-2 following lead optimization and experimental studies.
Diabetes mellitus (DM) and coronavirus disease 2019 (COVID-19) are public health issues worldwide, and their comorbidities trigger the progress to severe disease and even death in such patients. Globally, DM has affected an estimated 9.3% adults, and as of April 18, 2021, the World Health Organization (WHO) has confirmed 141,727,940 COVID-19 confirmed cases. The virus is spread via droplets, aerosols, and direct touch with others. Numerous predictive factors have been linked to COVID-19 severity, including impaired immune response and increased inflammatory response, among others. Angiotensin receptor blockers and angiotensin converting enzyme 2 have also been identified as playing a boosting role in both susceptibility and severity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Specifically, in DM patients, both their control and management during this pandemic is herculean as the restriction periods have markedly hampered the maintenance of means to control glycemia, hypertension, and neuroendocrine and kidney diseases. In addition, as a result of the underlyin cardio-metabolic and immunological disorders, DM patients are at a higher risk of developing the severe form of COVID-19 despite other comorbidities, such as hypertension, also potentially boosting the development of higher COVID-19 severity. However, even in non-DM patients, SARS-CoV-2 may also cause transient hyperglycemia through induction of insulin resistance and/or pancreatic β-cell injury. Therefore, a strict glucose monitoring of DM patients with COVID-19 is mandatory to prevent life-threatening complications.
Ethnopharmacological Relevance: The management of diabetes over the years has involved the use of herbal plants, which are now attracting interest. We assessed the antidiabetic properties of aqueous extract of C. purpureus shoots (AECPS) and the mechanism of action on pancreatic ß-cell dysfunction.Methods: This study was conducted using Thirty-six 36) male Wistar rats. The animals were divided into six equal groups (n = 6) and treatment was performed over 14 days. To induce diabetes in the rats, a single dose of 65 mg/kg body weight of alloxan was administered intraperitoneal along with 5% glucose. HPLC analysis was carried out to identified potential compounds in the extract. In vitro tests α-amylase, and α-glucosidase were analyzed. Body weight and fasting blood glucose (FBG) were measured. Biochemical parameters, such as serum insulin, liver glycogen, hexokinase, glucose-6-phosphate (G6P), fructose-1,6-bisphosphatase (F-1,6-BP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-ĸB), were analyzed. Additionally, mRNA expressions of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), B-cell lymphoma 2 (Bcl-2), and proliferating cell nuclear antigen (PCNA) were each evaluated.Results: This in vitro study showed inhibitory potency of Cenchrus purpureus extract (AECPS) as compared with the positive controls. AECPS showed a gradual decrease in alloxan-induced increases in FBG, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), G6P, F-1,6-BP, malondialdehyde (MDA), IL-6, TNF-α, and NF-ĸB and increased alloxan-induced decreases in liver glycogen, hexokinase, and high density lipoprotein (HDL-c). The diabetic control group exhibited pancreatic dysfunction as evidenced by the reduction in serum insulin, homeostasis model assessment of ß-cell function (HOMA-β), expressions of PI3K/AKT, Bcl-2, and PCNA combined with an elevation in homeostatic model assessment of insulin resistance (HOMA-IR). High performance liquid chromatography (HPLC) revealed 3-O-rutinoside, ellagic acid, catechin, rutin, and kaempferol in AECPS.Conclusion: AECPS showed efficient ameliorative actions against alloxan-induced pancreatic dysfunction, oxidative stress suppression as well as, inflammation, and apoptosis via the activation of PI3K/AKT signaling pathways.
The antioxidant and anti-proinflammatory activities of l-leucine were investigated on oxidative testicular injury, ex vivo. In vitro analysis revealed l-leucine to be a potent scavenger of free radicals, while inhibiting acetylcholinesterase activity. Oxidative injury was induced in testicular tissues using FeSO 4 . Treatment with l-leucine led to depletion of oxidativeinduced elevated levels of NO, MDA, and myeloperoxidase activity, with concomitant elevation of reduced glutathione and non-protein thiol levels, SOD and catalase activities. l-leucine caused a significant (p < 0.05) alteration of oxidative-elevated acetylcholinesterase and chymotrypsin activities, while concomitantly elevating the activities of ATPase, ENTPDase and 5′-nucleotidase. l-leucine conferred a protective effect against oxidative induced DNA damage. Molecular docking revealed molecular interactions with COX-2, IL-1 beta and iNOS. Treatment with l-leucine led to restoration of oxidative depleted ascorbic acid-2-sulfate, with concomitant depletion of the oxidative induced metabolites: D-4-Hydroxy-2-oxoglutarate, l-cystine, adenosine triphosphate, maleylacetoacetic acid, cholesteryl ester, and 6-Hydroxy flavin adenine dinucleotide. Treatment with l-leucine reactivated glycolysis while concomitantly deactivating oxidative-induced citrate cycle and increasing the impact-fold of purine metabolism pathway. l-leucine was predicted not to be an inhibitor of CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4, with a predicted LD 50 value of 5000 mg/Kg and toxicity class of 5. Additionally, l-leucine showed little or no in vitro cytotoxicity in mammalian cells. These results suggest the therapeutic potentials of l-leucine on oxidative testicular injury, as evident by its ability to attenuate oxidative stress and proinflammation, while stalling cholinergic dysfunction and modulating nucleotide hyrolysis; as well as modulate oxidative dysregulated metabolites and their pathways.
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