Aframomum melegueta secondary metabolites exhibit polypharmacology against SARS-CoV-2 drug targets: in vitro validation of furin inhibition.

COVID-19 pandemic is currently decimating the world's most advanced technologies and largest economies and making its way to the continent of Africa. Weak medical infrastructure and over-reliance on medical aids may eventually predict worse outcomes in Africa. To reverse this trend, Africa must re-evaluate the only area with strategic advantage; phytotherapy. One of the many plants with previous antiviral potency is against RNA viruses is Aframomum melegueta. In this study, one hundred (100) A. melegueta secondary metabolites have been mined and computational evaluated for inhibition of host furin, and SARS-COV-2 targets including 3C-like proteinase (Mpro /3CLpro ), 2'-O-ribose methyltransferase (nsp16) and surface glycoprotein/ACE2 receptor interface. Silica-gel column partitioning of A. melegueta fruit/seed resulted in 6 fractions tested against furin activity. Diarylheptanoid (Letestuianin A), phenylpropanoid (4-Cinnamoyl-3-hydroxy-spiro[furan-5,2'-(1'H)-indene]-1',2,3'(2'H,5H)-trione), flavonoids (Quercetin, Apigenin and Tectochrysin) have been identified as high-binding compounds to SARS-COV-2 targets in a polypharmacology manner. Di-ethyl-ether (IC50 = 0.03 mg/L), acetone (IC50 = 1.564 mg/L), ethyl-acetate (IC50 = 0.382 mg/L) and methanol (IC50 = 0.438 mg/L) fractions demonstrated the best inhibition in kinetic assay while DEF, ASF and MEF completely inhibited furin-recognition sequence containing Ebola virus-pre-glycoprotein. In conclusion, A. melegueta and its secondary metabolites have potential for addressing the therapeutic needs of African population during the COVID-19 pandemic.

Loranthus micranthus nanoparticles abates streptozotocin-instigated testicular dysfunction in Wistar rats: Involvement of glucose metabolism enzymes, oxido-inflammatory stress, steroidogenic enzymes/protein and Nrf2 pathway.

Loranthus micranthus (African mistletoe)-Loranthaceae family, is used in Nigerian traditional medicine for treating male infertility and lowering diabetic blood sugar levels. We investigated possible mechanism(s) involved in mitigation of L. micranthus leaves nanoparticles (LMLNPs) on streptozotocin (STZ)-induced testicular alterations. Type two diabetes mellitus (T2DM) was induced in male rats following 2 weeks feeding with fructose and single intraperitoneal injection of STZ. Control (nondiabetic) and (diabetic) rats received buffer only. Diabetic rats were treated with metformin or LMLNPs (two different doses) for 28 days. Hormonal profile, oxido-inflammatory stress parameters, glucose metabolism and steroidogenic enzymes/regulatory protein (StAR) and Nuclear factor erythroid 2-related factor 2 (Nrf2) protein in testes and sperm parameters were evaluated. Metformin and LMLNPs treatment significantly reduced blood glucose level in diabetic rats. Furthermore, LMLNPs enhanced glucose metabolism and testicular steroidogenic enzymes/protein, increased reproductive hormone levels and sperm functional parameters in diabetic rats. Additionally, LMLNPs suppressed testicular oxido-inflammatory stress biomarkers and inhibited lipid peroxidation in diabetic rats while augmenting Nrf2 pathway. Conclusively, LMLNPs potently reversed adverse effects of T2DM testicular dysfunction of rats. Use of LMLNPs in abating diabetic consequences proves an acceptable alternative to traditional crude extract preparations, as a result of better packaging and preservation.

Co-administration of Selenium Nanoparticles and Metformin Abrogate Testicular Oxidative Injury by Suppressing Redox Imbalance, Augmenting Sperm Quality and Nrf2 Protein Expression in Streptozotocin-Induced Diabetic Rats.

Selenium nanoparticles (SeNPs) and metformin (Met) elicit individually protective effects against testicular oxidative injury in diabetic rats. However, the combined effects of both compounds have not been investigated. We investigated the effects of SeNPs and Met individual/co-treatment on testicular oxidative injury in diabetic rats. Diabetes was induced by a single intraperitoneal administration of streptozotocin (STZ-40 mg/kg bwt). The rats were equally divided into 6 groups: Group one-non-diabetic; group two-diabetic untreated; and group six-non-diabetic received citrate buffer (2 mL/kg bwt), while group three, four, and five received SeNPs (0.1 mg/kg bwt), Met (50 mg/kg bwt), and SeNPs/Met combined respectively, for 42 days. Results revealed that SeNPs, as well as Met treatment significantly (p < 0.001), lowered blood glucose levels and improved relative organ weights in treated rats than those of the untreated group. Moreover, a synergistic effect was observed in the co-administration group. Additionally, combined treatment elicited better effect, in augmenting the pituitary and testicular hormone (LH, FSH, prolactin, and testosterone) levels, marker enzymes/protein associated with steroidogenesis (3-ßHSD, 17-ßHSD, and StAR protein), and sperm functional parameters than those of individual treatment groups, when compared with control. Furthermore, the combinatorial effects of SeNPs and Met surpassed their influence in attenuating testicular oxidative stress/inflammation and upregulation of Nrf2 protein expression in diabetic rats when compared with control. Overall, normal rats, co-treated with SeNPs and Met, did not reveal any deleterious effect. Therefore, SeNPs and Met combined treatment may better improve testes function in diabetic conditions than an individual regimen.