Experimental validation and molecular docking to explore the active components of cannabis in testicular function and sperm quality modulations in rats.

BACKGROUND: Data available support that ninety percent of male infertility cases are due to low sperm counts. There is a scarcity of data on the medicinal effects of cannabis on fertility. This study evaluated testicular function and sperm quality modulation with cannabis in rats. METHODOLOGY: Twenty-five male Wistar rats were randomly grouped into five: A, B, C, and D, each group have 5 rats. A (control): 0.2 ml 2% DMSO, B (vitamin C): 90 mg/kg body weight, C, D, and E were administered: 5 mg/kg, 10 mg/kg and 20 mg/kg body weight of ethanolic leaf extract of cannabis (ELEC) respectively. The rats were sacrificed 24 h after the last day of the 60 day oral administrations. Flavonoids were the predominant phytochemical present in the extract while quercetin, kemferol, silyman and gallic acid were identified. RESULTS: The results showed a significant improvement (p < 0.05) in sperm quality and a significant increase in the concentrations of follicle-stimulating hormone, luteinizing hormone, triglycerides, cholesterol, and total protein determination compared to the normal control. Similarly, there was a significant increase (p < 0.05) in the activities of acid phosphatase, alkaline phosphatase, and superoxide dismutase compared to the normal control. RAC-alpha serine/threonine-protein kinase (AKT1)-silymarin complexes (-8.30 kcal/mol) and androgen receptor (AR)-quercetin complexes (9.20 kcal/mol) had the highest affinity. CONCLUSION: The antioxidant effects of the flavonoids in the ethanolic extract of cannabis may have protected testicular and sperm cells from oxidative damage. Biochemical processes and histopathological morphology were preserved by cannabis. The docking prediction suggests that the bioactive principle of cannabis may activate the androgenic receptors. The androgenic receptor modulation may be attributed to silymarin and quercetin.

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Exhibits Antioxidant Mechanism for Abrogation of Cyclophosphamide-Induced Cardiac Damage and Oxidative Hepatorenal Toxicity in Rats.

Cyclophosphamide (CYP) is a potent DNA-interactive anticancer drug; however, its clinical drawbacks are chiefly associated with induction of oxidative multi-organ toxicity. Sitagliptin (STG) is an antidiabetic dipeptidyl peptidase-4 inhibitor drug with antioxidant efficacy. Herein, we have explored whether STG could abrogate the CYP-induced oxidative stress-mediated cardiac and hepatorenal toxicities in male rats. Sitagliptin (20 mg/kg, o.p) was administered to rats for 5 consecutive days against organ toxicities induced by CYP (200 mg/kg, i.p) on day 5 only. CYP induced marked injuries in the liver, kidney and heart underscored by prominent increases in serum activities of ALT, AST, LDH, creatine kinase and levels of urea, uric acid and creatinine, while albumin level significantly decreased compared to normal control rats. Further, CYP considerably reduced the activities of SOD, CAT, GPx, and levels of GSH, whereas MDA level increased significantly in comparison to control rats. These biochemical alterations were confirmed by multiple histopathological lesions in the tissues. Interestingly, the STG pretreatment abrogated the biochemical and histopathological changes induced by CYP. These results provide first evidence that repurposing STG may protect the liver, kidney and heart from the oxidative deterioration associated with CYP chemotherapy.

Evaluation of Antimalarial Potential of Extracts from Alstonia boonei and Carica papaya in Plasmodium berghei-Infected Mice.

Extracts of Alstonia boonei and Carica papaya are used in herbal medicine for the treatment of malaria. This work investigated the phytochemical, antioxidant, and antimalarial effects of hydromethanolic extracts of Alstonia boonei and Carica papaya. A four-day chemosuppressive test was conducted to assess the ability of the extracts to prevent establishment of infection. Three doses of the extracts were administered-100, 200, and 400 mg/kg bw-prior to Plasmodium berghei challenge. Change in body weight, parasitemia, packed cell volume (PCV), and mean survival time was determined. A three-day curative test was also carried out on Plasmodium berghei-infected mice to determine the effects of the plant extracts (200 mg/kg bw) on parasitemia and biochemical indices of liver and kidney functions, lipid metabolism, and oxidative stress. The study revealed that the extracts possessed phenolic compounds (34.13 ± 1.90 mg GAE/g for Alstonia boonei and 27.99 ± 1.46 mg GAE/g for Carica papaya) and flavonoids (19.47 ± 1.89 mg QE/g for Alstonia boonei and 18.24 ± 1.36 mg QE/g for Carica papaya). In vitro antioxidant activity measured as total antioxidant power, total reducing power, and DPPH radical scavenging activity showed that the extracts possessed higher antioxidant activity than the reference compounds. The outcome of the chemosuppressive test revealed that whereas Plasmodium berghei-infected mice had high parasitemia, decreased mean survival time, exhibited loss of weight, and had low PCV, treatment with the extracts reversed the effects in a concentration-dependent manner. Similarly, the curative test revealed that the extracts significantly suppressed parasitemia compared with the malaria negative control group. This was mirrored by reversal of indices of hepatic toxicity (AST, ALT, and ALP levels), nephropathy (urea and creatinine levels), oxidative stress (SOD, CAT, GPx, GSH, and lipid peroxides), and dyslipidemia (TC, HDL, and TG levels and HMG-CoA reductase activity) in infected but treated mice compared with negative control. Put together, the results of this study demonstrate that the extracts of Alstonia boonei and Carica papaya possess antimalarial properties and are able to ameliorate metabolic dysregulations that characterize Plasmodium berghei infection. The phytoconstituents in these extracts are believed to be responsible for the pharmacological activity reported in this study.