Potential Curative Effects of Aqueous Extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on Acetaminophen-Induced Liver Injury in Mice.

Background: Acetaminophen-induced liver injury remains a significant public health problem because available treatments are limited due to their adverse effects. Medicinal plants, which are an important source of bioactive molecules, could be an alternative treatment for liver disease. Objective: This study was designed to investigate the curative effect of aqueous extracts of Cissus quadrangularis (Vitaceae) and Jatropha gossypiifolia (Euphorbiaceae) on acetaminophen-induced liver injury in mice. Methods: Mice were divided into groups and treated with distilled water, silymarin (50 mg/kg), a reference hepatoprotective agent, and aqueous extracts of C quadrangularis and J gossypiifolia (50 and 100 mg/kg, PO, respectively). These substances were given as a single daily dose 4 hours after acetaminophen administration (300 mg/kg, PO) for 2 days. Mice were humanely put to death 24 hours after the last dose and serum alanine aminotransferase and aspartate aminotransferase activities, total bilirubin and protein levels, reduced glutathione, superoxide dismutase, malondialdehyde, catalase, and nitrite tissue levels were assessed. Histology of the livers of the mice was performed by hematoxylin and eosin staining. Results: Acetaminophen administration induced a significant (P < 0.05) mean (SEM) body weight loss (-14.45% [5.92%]), a significant elevation of alanine aminotransferase activity (15.08%), total protein and bilirubin levels (25.80%), and a significant (P < 0.05) increase in liver superoxide dismutase (67.71%), catalase (63.00%), glutathione (40.29%), malondialdehyde (30.67%), and nitrite levels compared with the control group. In curative treatment, C quadrangularis and J gossypiifolia (50 and 100 mg/kg) significantly (P < 0.05) reduced mean (SEM) body weight loss (16.67% [7.16%] and 1.25% [0.51%], respectively), serum alanine aminotransferase activity (17.62% and 11.14%, respectively), bilirubin level (29.62% and 49.14%, respectively) compared with acetaminophen group, and J gossypiifolia normalized serum total protein level. Both extracts significantly (P < 0.05) reduced the levels of glutathione and malondialdehyde and normalized that of nitrite, superoxide dismutase, and catalase compared with the acetaminophen group. Hepatocyte necrosis and inflammatory cell infiltration were remarkably reduced by the plant extracts. Conclusions: The results obtained are evidence in favor of the development of a formulation based on the extracts of these plants against liver diseases.

Serological Evidence of Hepatitis B and E and Dengue Coinfection in Chadian Patients and Impact on Lipidemia Profile.

Objective: Viral hepatitis is an endemic disease in Chad. However, few studies have documented coinfection cases and their impact on cardiovascular risk. This study is aimed at analyzing hepatitis B, E and dengue coinfection in a Chadian cohort and gauge its effect on lipidemia. Patients and Methods. From February to May 2021, 179 subjects were recruited from the Department of Gastroenterology and Internal Medicine of the National Reference University Hospital of N'Djamena and tested for viral hepatitis markers, including HBsAg and IgM/IgG anti-HEV and dengue infection, using the NS1/IgM/IgG kit. Serum transaminases and biomarkers of lipid profiles were assayed by colorimetry, and atherogenic indexes (AI) and coronary risk (CRI) were calculated. Results: Of the 179 subjects surveyed, 21.22% (38/179) tested positive for hepatitis B, 20% (27/135) for hepatitis E, and 1.66% (2/120) for dengue. However, most of the patients were found to be asymptomatic. Hepatitis B/E coinfection was more frequent in the study population (5.02%; 9/179) than dengue/hepatitis E coinfection (0.83%; 1/120; IgM). The prevalence of anti-HEV IgG antibodies was higher (18.52%) than that of IgM (1.48%). Furthermore, IgG antibodies levels in HEV-monoinfected subjects (11.05 ± 1.93 IU/mL, N = 15) were significantly higher (p < 0.05) than in coinfected patients (5.40 ± 1.31 IU/mL, N = 9). Subjects coinfected with HEV/HBV were associated with a significantly higher risk of lipodystrophy (coronary risk: 88.89% vs. 35.3%, relative risk (RR) = 2.55; p = 0.014), than HEV-monoinfected subjects, as evidenced by higher mean levels of triglycerides levels (219.88 ± 14.67 mg/dL vs. 191.82 ± 4.66 mg/dL, p < 0.05), more reduced HDL-C levels (9.05 ± 1.62 mg/dL vs. 18.93 ± 2.35 mg/dL, p < 0.05), increased mean CRI (13.81 ± 2.39 vs. 6.89 ± 1.93, p < 0.01), and AI (1.46 ± 0.10 vs. 1.05 ± 0.05, p < 0.01) values. However, they had normal transaminase values and a lower risk of developing a liver injury, although not significant (alanine aminotransferase: 0% vs. 29.4%, RR = 1, p = 0.128; aspartate aminotransferase: 0% vs. 5.88%, p = 1) than this group. Conclusion: HBV/HEV coinfection is frequent in the Chadian cohort and associated with an important risk of dyslipidemia. Further research is required to elucidate the mechanism of action.

In silico and in vitro screening of licensed antimalarial drugs for repurposing as inhibitors of hepatitis E virus.

ABSTRACT: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00093-y.

Natural limonoids protect mice from alcohol-induced liver injury.

Background Alcoholic liver disease (ALD) is regarded as a global health problem with limited therapeutic options. Previous studies highlighted some anticancer, antiviral, and hepatoprotective activities of limonoids, but the effects of these compounds on ALD remain unknown. The present study aimed to evaluate the effect of some natural limonoids on ethanol-induced liver injury. Methods Thirty-five albino mice (Mus musculus) were administered with 40% ethanol in the presence or absence of the different limonoids [including three havanensin-type limonoids, TS1, TS3, Rubescin D isolated from an African medicinal plant, Trichilia rubescens Oliv. (Meliaceae), and one limonin], or silymarin at 50 mg/kg for 3 days. Thereafter, the effect of the most active compound was evaluated in a chronic model of ALD. For this purpose, 24 mice with each group consisting of six mice were administered orally with 40% ethanol and limonoid at different doses (50, 75, and 100 mg/kg) for 28 days. Finally, biochemical parameters such as alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), triglyceride (TG), and tumor necrosis factor α (TNF-α) levels were quantified in liver homogenates. Results All tested limonoids significantly (p < 0.01) reduced ALT levels relative to the negative control in the acute model. However, in comparison to other limonoids, limonin at 50 and 75 mg/kg significantly reduced TG, MDA, and TNF-α levels (1.8-fold); alleviated leukocyte infiltration in liver tissue; significantly increased the activity of SOD; and decreased those of CAT better than silymarin used as a positive control at 50 mg/kg. Conclusions These data suggest that limonin possesses protective effects on long-term alcohol poisoning partially due to antioxidant and anti-inflammatory mechanisms.

Hepatitis C in Cameroon: What is the progress from 2001 to 2016?

Chronic hepatitis C is a major public health problem in sub-Saharan countries and particularly in Cameroon where the prevalence rate is around 7.6% in the age group of 55-59 years. Recent investigations into this infection allowed defining a national seroprevalence, characterizing virological and biological profiles of infected patients and identifying medicinal plants of potential interest in hepatitis C therapy. However, in Cameroon, no existing report currently presents a good overview of hepatitis C research in relation to these parameters. This review seeks to discuss major findings published since 2001 that have significantly advanced our understanding of the epidemiology and treatment of hepatitis C in Cameroonian patients and highlight the major challenges that remain to overcome. We performed a systematic search in Pubmed and Google Scholar. Studies evaluating prevalence, treatment, coinfection, and genetic diversity of HCV infection in Cameroon were included. Studies suggest that HCV prevalence in Cameroon would be low (around 1.1%) with a lot of disparities according to regions and age of participants. Elders, pregnant women, blood donors, health care workers, patients on hemodialysis, and homozygous sickle cell patients have been identified as risk groups. Moreover, HCV/HBV coinfection was found more prevalent than HCV/HIV coinfection. Phylogenic studies reported circulation of three main genotypes such genotypes 1, 2, and 4 but little is known about antiviral candidates from the Cameroonian pharmacopeia. In conclusion, some epidemiological data prove that hepatitis C in Cameroon is well known but efforts are still necessary to prevent or control this infection.