Water-soluble phenolics from Phoenix dactylifera fruits as potential reno-protective agent against cisplatin-induced toxicity: pre- and post-treatment strategies.

Nephrotoxicity is the major side effect of cisplatin, an effective platinum-based chemotherapeutic drug that is applicable in the treatment of several solid-tissue cancers. Studies have indicated that certain water-soluble phenolics offer renal protection. Thus, this study investigates the role of pre and post-treatment of rats with water-soluble phenolics from Phoenix dactylifera (PdP) against nephrotoxicity induced by cisplatin. Rats were either orally pretreated or post-treated with 200 mg/kg body weight of PdP before or after exposure to a single therapeutic dose of cisplatin (5 mg/kg body weight) for 7 successive days intraperitoneally. The protective effects of PdP against Cisplatin-induced nephrotoxicity was based on the evaluation of various biochemical and redox biomarkers, together with histopathological examination of kidney tissues. The composition, structural features, and antioxidative influence of PdP were determined based on chromatographic, spectroscopic, and in vitro antioxidative models. Cisplatin single exposure led to a substantial increase in the tested renal function biomarkers (uric acid, creatinine, and urea levels), associated with an increase in malondialdehyde indicating lipid peroxidation and a significant decline (p < 0.05) in reduced glutathione (GSH) levels in the renal tissue when compared with the control group. A marked decline exists in the kidney antioxidant enzymes (catalase, SOD, and GPx). Nevertheless, treatment with PdP significantly suppressed the heightened renal function markers, lipid peroxidation, and oxidative stress. Spectroscopic analysis revealed significant medicinal phenolics, and in vitro tests demonstrated antioxidative properties. Taken together, results from this study indicate that pre- and/or post-treatment strategies of PdP could serve therapeutic purposes in cisplatin-induced renal damage.

Kaempferol mitigates reproductive dysfunctions induced by Naja nigricollis venom through antioxidant system and anti-inflammatory response in male rats.

Naja nigricollis Venom (NnV) contains complex toxins that affects various vital systems functions after envenoming. The venom toxins have been reported to induce male reproductive disorders in envenomed rats. This present study explored the ameliorative potential of kaempferol on NnV-induced male reproductive toxicity. Fifty male wistar rats were sorted randomly into five groups (n = 10) for this study. Group 1 were noted as the control, while rats in groups 2 to 5 were injected with LD50 of NnV (1.0 mg/kg bw; i.p.). Group 2 was left untreated post envenomation while group 3 was treated with 0.2 ml of polyvalent antivenom. Groups 4 and 5 were treated with 4 and 8 mg/kg of kaempferol, respectively. NnV caused substantial reduction in concentrations of follicle stimulating hormone, testosterone and luteinizing hormone, while sperm motility, volume and counts significantly (p < 0.05) decreased in envenomed untreated rats. The venom enhanced malondialdehyde levels and substantially decreased glutathione levels, superoxide dismutase and glutathione peroxidase activities in the testes and epididymis of envenomed untreated rats. Additionally, epididymal and testicular myeloperoxidase activity and nitric oxide levels were elevated which substantiated severe morphological defects noticed in the reproductive organs. However, treatment of envenomed rats with kaempferol normalized the reproductive hormones with significant improvement on sperm functional parameters. Elevated inflammatory and oxidative stress biomarkers in testis and epididymis were suppressed post kaempferol treatment. Severe histopathological lesions in the epididymal and testicular tissues were ameliorated in the envenomed treated groups. Results highlights the significance of kaempferol in mitigating reproductive toxicity induced after snakebite envenoming.

Kaempferol from Moringa oleifera demonstrated potent antivenom activities via inhibition of metalloproteinase and attenuation of Bitis arietans venom-induced toxicities.

Bitis arietans venom (BAV) can induce severe pathophysiological disorders after envenoming. However, studies have shown that the Moringa oleifera fraction is effective against BAV toxicities and contains bioactive compounds with significant antivenom potency. This research aimed to identify the main active antivenom compound in the M. oleifera fraction responsible for neutralizing the toxicities induced by BAV. The compounds identified from M. oleifera fraction were docked in silico against the catalytic site of the Snake Venom Metalloproteinase (SVMP) to determine the lead inhibitor compound. The antivenom potency of the lead inhibitor compound was tested against BAV toxicities and metalloproteinase isolated from BAV using in vitro and in vivo methods, while EchiTab-Plus polyvalent antivenom served as a standard drug. The in silico prediction revealed kaempferol as the lead inhibitor compound with a docking score of -7.0 kcal/mol. Kaempferol effectively inhibited metalloproteinase activity at 0.2 mg/ml, compared to antivenom (0.4 mg/ml) and demonstrated significant antihaemorrhagic, antihaemolytic and coagulant effects against BAV activities. Furthermore, kaempferol showed a significant dose-dependent effect on altered haematological indices observed in rats challenged with LD50 of BAV. Envenomed rats also showed an increase in oxidative stress biomarkers and antioxidant enzyme activity in the heart and kidney. However, treatment with kaempferol significantly (P < 0.05) decreased malondialdehyde levels and SOD activity with concomitant enhancement of glutathione levels. Severe histopathological defects noticed in the organ tissues of envenomed rats were ameliorated after kaempferol treatment. Kaempferol is identified as the main active antivenom compound in M. oleifera, and this research highlights the potential of the compound as an effective alternative to snakebite treatment.

Functional Bioactivities of Soluble Seed Proteins from Two Leguminous Seeds.

Storage proteins from Sphenostylis stenocarpa and Phaseolus lunatus were fractionated, and their in vitro bioactivities were investigated. Albumin, globulin, prolamin, and glutelin constituents of the respective seeds were successively fractionated using the modified Osborne method. Phenylmethylsulfonyl fluoride (1 mM) was used as a protease inhibitor. The antioxidant, anti-inflammatory, and acetylcholinesterase-inhibitory activities of the protein fractions were evaluated using different appropriate techniques. Globulin was the predominant fraction, with a yield of 43.21±0.01% and 48.19±0.03% for S. stenocarpa and P. lunatus, respectively, whereas prolamin was not detected in both seeds. The protein fraction markedly scavenges hydroxyl radicals, nitric oxide radicals, and 2,2-diphenyl-1-picryldydrazyl radicals with concomitant high free radical-reducing power. Albumin and globulin fractions elicited the highest acetylcholinesterase-inhibitory potential of 48.75% and 49.75%, respectively, indicating their great application potential in managing neurodegenerative diseases. In this study, the albumin, globulin, and glutelin fractions of these underutilized legumes showed great analeptic bioactivities, which could be utilized as health-promoting dietary supplements/products.

Efficacy of selected Nigerian tropical plants in the treatment of COVID-19: in silico and in vitro investigations.

The whole world is still challenged with COVID-19 pandemic caused by Coronavirus-2 (SARS-CoV-2) which has affected millions of individuals around the globe. Although there are prophylactic vaccines being used, till now, there is ongoing research into discovery of drug candidates for total eradication of all types of coronaviruses. In this context, this study sought to investigate the inhibitory effects of six selected tropical plants against four pathogenic proteins of Coronavirus-2. The medicinal plants used in this study were selected based on their traditional applications in herbal medicine to treat COVID-19 and related symptoms. The biological activities (antioxidant, free radical scavenging, and anti-inflammatory activities) of the extracts of the plants were assessed using different standard procedures. The phytochemicals present in the extracts were identified using GCMS and further screened via in silico molecular docking. The data from this study demonstrated that the phytochemicals of the selected tropical medicinal plants displayed substantial binding affinity to the binding pockets of the four main pathogenic proteins of Coronavirus-2 indicating them as putative inhibitors of Coronavirus-2 and as potential anti-coronavirus drug candidates. The reaction between these phytocompounds and proteins of Coronavirus-2 could alter the pathophysiology of COVID-19, thus mitigating its pathogenic reactions/activities. In conclusion, phytocompounds of these plants exhibited promising binding efficiency with target proteins of SARS-COV-2. Nevertheless, in vitro and in vivo studies are important to potentiate these findings. Other drug techniques or models are vital to elucidate their compatibility and usage as adjuvants in vaccine development against the highly contagious COVID-19 infection.

Covid-19 treatment: Investigation on the phytochemical constituents of Vernonia amygdalina as potential Coronavirus-2 inhibitors.

The upsurge in the current cases of COVID-19 poses a major threat on human health and population all over the globe. The emergence of new infectious diseases and increase in frequency of drug resistant viruses demand effective and novel therapeutic agents. In this study, we used bioinformatics approach to investigate the possible inhibitory potentials of phytochemical constituents of Vernonia amygdalina towards coronavirus-2 major protease. Pharmacodynamics, pharmacokinetics and toxicological profiles of the compounds were also examined using the pkCSM server. All the phytochemicals showed good binding affinity to the binding pocket of PDB ID 6LU7. It was observed that veronicoside A exhibited the highest binding affinity when compared to remdesivir, hydroxy-vernolide, vernodalin, vernodalol, and vernolide. The amino acids LEU272, LEU287, GLY275, TYR237, LYS236, THR198, THR199, ARG131, and LYS5 were showed as the key residues for veronicoside A binding to human SARS-COV2 major protease. The Pharmacodynamics and pharmacokinetics results suggested that all the tested phytochemicals have significant drug likeness properties and they could be absorbed through the human intestine. Furthermore, all the tested phytochemicals are not hepatoxic and also exhibited non or relatively low toxic effects in human. Taken together, the results of this study indicated that all the tested phytochemicals are potential putative inhibitors of SARS-COV2 major protease with non or low toxicity effects. However, further experimental and clinical studies are needed to further explore their activities and validate their efficacies against COVID-19.