Re: Potential of Wild Egyptian Artichoke for Hepatitis C Treatment

Wild Egyptian Artichoke (Cynara cardunculus var. sylvestris, Asteraceae) Hepatitis C Treatment Date: 10-13-2017 HC# 041756-578 Elsebai MF, Abass K, Hakkola J, Atawia AR, Farag MA. The wild Egyptian artichoke as a promising functional food for the treatment of hepatitis C virus as revealed via UPLC-MS and clinical trials. Food Funct. 2016;7(7):3006-3016. Hepatitis C virus (HCV) is the most common chronic bloodborne infection. There are 7 major HCV genotypes (1-7), which vary regionally. Water extracts of wild Egyptian artichoke (wild cardoon; Cynara cardunculus var. sylvestris, Asteraceae) (WEA) leaves are used traditionally in Egypt for their choleretic (increasing bile secretion) and hepatoprotective (liver-protective) effects. In addition, 2 sesquiterpene lactones (cynaropicrin and grosheimol) isolated from WEA leaves can inhibit HCV infection in vitro. However, one study evaluating an artichoke extract, Hepar SL forte® (Sertürner Arzneimittel GmbH; Gütersloh, Germany), in 17 patients with HCV reported no benefit. The purpose of this study was to determine whether WEA leaf extract is active against HCV and to identify the bioactive chemicals. The WEA leaves used in this study were collected in Sinai, Egypt, in October 2011. The leaves were freeze-dried, powdered, and put into 1.5-g packets for infusion as a tea. The tea was made by steeping in boiling water for 7 minutes. For analytical analysis, the leaves were boiled in water and freeze-dried to create the extract. Clinical Investigation Patients (n = 15; average age, 51 years) with serological-confirmed HCV participated in this pilot study conducted at Mansoura University; Mansoura, Egypt. In addition, 5 non-infected people served as controls. Excluded subjects met the following criteria: therapy with an interferon within the last 6 months prior to the start of the study, chronic hepatitis B co-infection, liver cirrhosis Child B or C, pregnancy or breastfeeding, and/or other serious health conditions. Included patients drank the WEA tea infusion 3x/day for 3 months. The primary outcome was the rate of alanine aminotransferase (ALT) normalization after 3 months. Secondary outcomes included changes in ALT, aspartate aminotransferase (AST), and bilirubin levels; quantitative HCV RNA levels; subjective symptoms frequently associated with chronic hepatitis C (anorexia, muscle and joint pains, fatigue, nausea, and weight loss); safety; tolerability; and compliance. Blood was drawn for analysis at baseline and at 1, 2, and 3 months, then again at 6 months after stopping WEA therapy. The levels of AST and ALT correlated with the degree of cellular liver injury. At 3 months, 12 patients were HCV-free and had normal AST and ALT levels. There was a linear decrease in ALT and AST levels over time; there was no change in AST or ALT levels in the control subjects. The only reported adverse event was "pseudo-arthritis," which occurred in 6 of 20 participants (4 patients with HCV and 2 control subjects), and disappeared when the treatment ended. Excellent tolerability was reported by 80% of participants. Symptoms of HCV infections improved at 2 months. These findings contradict the findings with Hepar SL forte. Analytical Analysis Since the clinical findings with WEA differed from the findings with Hepar SL forte, the authors hypothesized that may be due to the artichoke variety (wild Egyptian vs. German). The authors used ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC/ESI-QTOF-MS) to quantitate the differences in their composition. The analysis revealed 57 metabolites in the WEA, including flavonoids (n = 8), hydroxy cinnamates (phenolic acids, n = 11), saponins (n = 6), sesquiterpenes (n = 6), oxylipids (n = 2), and organic acids (n = 5). The Hepar SL forte had a completely different metabolite profile pattern. They both had a different amount of grosheimol derivatives, which has been shown to inhibit HCV. Both extracts had similar levels of cynaropicrin. Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) produced similar results. Interaction with Drug-metabolizing Enzymes Human liver samples of 10 Caucasian male and female donors were obtained from the University Hospital of Oulu; Oulu, Finland. The effects of WEA on cytochrome P450 (CYP) liver enzymes were evaluated. WEA strongly inhibited CYP2D6 and CYP2C19, and moderately inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A4. This indicates a possibility for herb-drug interactions in this population, and that WEA may alter the metabolism of certain drugs. Studies are needed to investigate other populations. The authors conclude that both WEA and German artichoke extracts had different genotypes, and the WEA UPLC-MS fingerprint was unique. These differences could be attributed to the geographical origin, storage, harvesting time, or seasonal variation and need to be investigated further. The preliminary clinical findings of WEA on HCV are promising. The study needs to be repeated in a larger population. Funding for the study was provided by the Alexander von Humboldt Foundation (Bonn, Germany) and the Science and Technology Development Fund (STDF), Ministry of Scientific Research (Cairo, Egypt). —Heather S. Oliff, PhD