Abstract
Millions of people are still infected with hepatitis C virus (HCV) nowadays. Although recent antivirals targeting HCV proteins are very efficient, they are not affordable for many people infected with this virus. Therefore, new and more accessible treatments are needed. Several Ivorian medicinal plants are traditionally used to treat “yellow malaria”, a nosological category including illness characterized by symptomatic jaundice such as hepatitis. Therefore, some of these plants might be active against HCV. An ethnobotanical survey in Côte d’Ivoire allowed us to select such medicinal plants. Those were first extracted with methanol and tested for their anti-HCV activity. The most active ones were further studied to specify their IC50 and to evaluate their toxicity in vitro. Greener solvents were tested to obtain extracts with similar activities. Following a phytochemical screening, tannins of the most active plants were removed before re-testing on HCV. Some of these tannins were identified by UPLC-MS and pure molecules were tested against HCV. Out of the fifteen Ivorian medicinal plants selected for their putative antiviral activities, Carapa procera DC. and Pericopsis laxiflora (Benth. ex Baker) Meeuwen were the most active against HCV (IC50: 0.71 and 0.23 μg/ml respectively) and not toxic for hepatic cells. Their crude extracts were rich in polyphenols, including tannins such as procyanidins A2 which is active against HCV. The same extracts without tannin lost their anti-HCV activity. Replacing methanol by hydro-ethanolic solvent led to tannins-rich extracts with similar antiviral activities, and higher than that of aqueous extracts.
Highlights
Hepatitis C is a major cause of chronic hepatitis often associated with complications, such as liver cirrhosis and hepatocellular carcinoma (Levrero, 2006; Messina et al, 2015)
Several other compounds were used as standards for Thin Layer Chromatography (TLC) or Ultra-High Performance Liquid Chromatography (UPLC): quercetin and quinin were from Merck (Germany), gallic acid, stigmasterol and glycyrrhetic acid were from Extrasynthése (France), (−)-epicatechin, (+)-catechin, aloin and ellagic acid were from Sigma (Germany), (−)-EGC was from Chromadex (United States), (−)-EGCG was from Selleckchem (United States)
Many of the plants screened here for putative antiviral activity have been reported to be used against malaria and/or have shown antiplasmodial activity (Table 1)
Summary
Hepatitis C is a major cause of chronic hepatitis often associated with complications, such as liver cirrhosis and hepatocellular carcinoma (Levrero, 2006; Messina et al, 2015). Treatments with direct-acting antiviral (DAA) agents targeting viral proteins have been established. These therapies with high rates of sustained viral response against all HCV genotypes and very few side effects are driven by DAAs that target viral proteins NS3/4A protease, NS5A, and NS5B polymerase (Falade-Nwulia et al, 2017). There is a risk of selecting viral variants resistant to DAAs leading to failure of the therapy, which will require new treatments (Pawlotsky, 2016). These treatments are very expensive and will benefit only a very small proportion of patients (Graham and Swan, 2015). The search for such compounds and extracts is still needed to treat the vast majority of patients in the coming decades
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