Sclerocarya birrea is used in folk medicine for the treatment of inflammatory disorders. The effect of the stem bark aqueous and methanol extracts of S. birrea (150 or 300 mg/kg) was evaluated on carrageenan-, histamine- or serotonin-induced paw oedema in rats. The methanol extract of S. birrea (300 mg/kg) being the most active, exhibited a maximum inhibition of 75.45 and 55.31% on carrageenan- and histamine-induced inflammation, respectively. When administered at 300 mg/kg, the methanol extract of S. birrea also exhibited 80.68% inhibition on the 10th day and 54.43% inhibition on the 21st day in formalin- or complete Freund's adjuvant (CFA)-induced paw oedema in rats. GSH level was significantly increased (75.14%), while MAD level was significantly decreased (31.22%) in the liver of CFA rats treated with S. birrea (300 mg/kg). The results suggest that the anti-inflammatory activity of the aqueous and methanol extracts of S. birrea is due to the inhibition of histamine and prostaglandin pathways and to its antioxidant activity.

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Objective: Allanblackia gabonensis (Guttiferae) is a plant used in traditional medicine to treat some inflammatory diseases. As oxidative stress promotes the development of acetaminophen (APAP)-induced hepatotoxicity, the aim of the present study was to evaluate the hepato-nephroprotective and antioxidant effect of aqueous extract of A.gabonensis on APAP-induced liver and kidney damage. Methods: A.gabonensis was given daily per os during 7 days, followed by APAP which was given 2 h after the 6 th dose for preventive effect, whereas for curative testing A.gabonensis was administrated 30 min after APAP (2 g/kg). Preventive and curative effects were observed by following biochemical parameters analysis: transaminases, bilirubin, creatinine, nitric oxide, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Results: The aqueous extract of A.gabonensis at the dose of 100 and 200 mg/kg produced significant hepato-nephroprotective activity by reducing the serum effect of MDA while it significantly produced an increase in enzymatic antioxidant activities (SOD and CAT) and non enzymatic antioxidant (GSH) levels. A.gabonensis also showed a significant decrease in transaminase, bilirubin and creatinine in APAP intoxicicated rats at the doses of 100 and 200 mg/kg. Conclusion: From this study it can be concluded that aqueous extract of A.gabonensis may possess hepato-nephroprotective activities which can be partly attributed to its antioxidant properties.

Hepatitis E virus (HEV) infection is emerging in Cameroon and represents one of the most common causes of acute hepatitis and jaundice. Moreover, earlier reports showed evidence of falciparum malaria/HEVcoexistence. Although the Sofosbuvir/Ribavirin combination was recently proposed in the treatment of HEV-infected patients, no specific antiviral drug has been approved so far, thereby urging the search for new therapies. Fortunately, drug repurposing offers a good alternative to this end. In this study, we report the in silico and in vitro activities of 8 licensed antimalarial drugs and two anti-hepatitis C virus agents used as references (Sofosbuvir, and Ribavirin), for repurposing as antiviral inhibitors against HEV. Compounds were docked against five HEV-specific targets including the Zinc-binding non-structural protein (6NU9), RNA-dependent RNA polymerase (RdRp), cryoEM structure of HEV VLP, genotype 1 (6LAT), capsid protein ORF-2, genotype 3 (2ZTN), and the E2s domain of genotype 1 (3GGQ) using the iGEMDOCK software and their pharmacokinetic profiles and toxicities were predicted using ADMETlab2.0. Their in vitro effects were also assessed on a gt 3 p6Gluc replicon system using the luciferase reporter assay. The docking results showed that Sofosbuvir had the best binding affinities with 6NU9 (− 98.22 kcal/mol), RdRp (− 113.86 kcal/mol), 2ZTN (− 106.96 kcal/mol), while Ribavirin better collided with 6LAT (− 99.33 kcal/mol). Interestingly, Lumefantrine showed the best affinity with 3GGQ (-106.05 kcal/mol). N -desethylamodiaquine and Amodiaquine presented higher binding scores with 6NU9 (− 93.5 and − 89.9 kcal/mol respectively vs − 80.83 kcal/mol), while Lumefantrine had the greatest energies with RdRp (− 102 vs − 84.58), and Pyrimethamine and N -desethylamodiaquine had stronger affinities with 2ZTN compared to Ribavirin (− 105.17 and − 102.65 kcal/mol vs − 96.04 kcal/mol). The biological screening demonstrated a significant ( P < 0.001) antiviral effect on replication with 1 µM N-desethylamodiaquine, the major metabolite of Amodiaquine. However, Lumefantrine showed no effect at the tested concentrations (1, 5, and 10 µM). The biocomputational analysis of the pharmacokinetic profile of both drugs revealed a low permeability of Lumefantrine and a specific inactivation by CYP3A2 which might partly contribute to the short half-time of this drug. In conclusion, Amodiaquine and Lumefantrine may be good antimalarial drug candidates for repurposing against HEV. Further in vitro and in vivo experiments are necessary to validate these predictions. Graphic abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40203-021-00093-y.

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