Potential of Wild Egyptian Artichoke for Hepatitis C Treatment

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).

Resource:

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.

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Analysis of Helichrysum (Immortelle) Chemistry, Antioxidant Activity, and Chemotaxonomy

Traditionally, helichrysum (immortelle; Helichrysum italicum, Asteraceae) has been used for the treatment of scars and cuts, as well as used as a liver stimulant and diuretic. The essential oil of helichrysum has been found to have anti-inflammatory, antioxidant, fungicidal, and astringent effects. As an emollient and fragrance in the cosmetic and perfume industry, the chemical composition of helichrysum essential oil has been somewhat characterized. The aim of this study was to further characterize the chemical content and antioxidant activity of helichrysum aerial parts and to assess the chemotaxonomy of the H. italicum taxa.

The flowering aerial parts of helichrysum (H. italicum ssp. italicum) were collected in May 2011, near Valdanos, Montenegro. The air-dried aerial parts of the plant were extracted with 45% ethanol and dried. The air-dried flowering upper parts of helichrysum were submitted to hydrodistillation to produce the essential oil.

The essential oil was characterized by using chromatography and mass spectrometry techniques. Principal component analysis (PCA) and cluster analysis (CA) was used to compare the main chemical constituents identified in this study with 16 different H. italicum taxa. The dried ethanol extract was dissolved in an aqueous solution for analysis of total phenolics and flavonoids. Both the essential oil and the ethanol extract were assessed for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The ethanol extract was also evaluated for inhibition of hydroxyl radical (OH) generation.

The essential oil yield was found to be 0.15 ± 0.02%. A total of 27 compounds were identified, which represented 96.1% of the total oil composition. Most of the compounds were oxygenated monoterpenes (43.9%) and sesquiterpene hydrocarbons (41.2%). [Note: There are discrepancies between the article text and the data in Table 1, which lists these as 43.1% and 42.2%, respectively.] The major compounds found in the oil were neryl acetate (28.2%), neryl propionate (9.1%), γ-curcumene (17.8%), and ar-curcumene (8.3%). [Note: There are discrepancies for three of these compounds among the abstract, article text, and data in Table 1, which lists these as neryl acetate (29.2%), neryl propionate (10.1%), and γ-curcumene (18.8%).] Other compounds found included α-selinene (3.9%), isoitalicene (3.2%), thymol (2.8%), and α-cedrene (2.4%). These concentrations are consistent with previous reports for this plant subspecies.

PCA indicated that H. italicum ssp. italicum from Greece, H. italicum ssp. serotinum from the Iberian Peninsula, and plant material collected from the region of former Yugoslavia could all be clearly differentiated from one another based on different dominant chemical components. Helichrysum italicum ssp. italicum and H. italicumssp. microphyllum were phylogenetically similar and had similar dominant chemical components. These and other taxa consisting of the main chemical components (e.g., neryl acetate) were found to represent four chemotypes. Two of these chemotypes had subchemotypes. CA indicated similar results in terms of the differentiation of H. italicum ssp. italicum from Greece and H. italicum ssp. serotinum from the Iberian Peninsula. The other taxa were classified in a similar way as that found by PCA, but with some differences, especially for the italicum subspecies.

The yield of the aqueous ethanol extract was 19.77%. The total phenolics and total flavonoids of this extract were found to be 31.97 ± 1.42 mg gallic acid equivalents (GAE)/g of dry extract and 20.68 ± 0.66 mg quercetin equivalents (QE)/g of dry extract, respectively. The radical scavenging capacity (RSC) of the ethanol extract and the essential oil was dose-dependent. In terms of DPPH RSC, the half maximal inhibitory concentration (IC50) was significantly lower (more effective) for the ethanol extract (0.99 µg/ml) compared to the essential oil (1.76 mg/ml) (P value not given). [Note: Table 3 lists the essential oil IC50 as 1.37 mg/ml.] The extract had results that were similar to propyl gallate and quercetin dihydrate. Only the ethanol extract was evaluated for OH scavenging capacity (IC50 = 26.47 µg/ml), but the RSC was significantly less effective compared to its DPPH RSC (P value not given).

The chemical constituents identified from the essential oil of helichrysum aerial parts in this study are consistent with reports assessing the main chemical components of this plant subspecies. A chemotaxonomic analysis suggests that different regions of the world can affect the chemistry of the essential oil. The authors recommend classifying the species further based on these chemical differences. The authors also indicate that helichrysum extracts and essential oils may be effective natural antioxidants for foodstuff and pharmaceuticals. Further studies should be conducted on how differences in chemical composition may affect biological activity, fragrance, and other qualities of the helichrysum extracts and essential oils.

Resource:

Kladar NV, Anačkov GT, Rat MM, et al. Biochemical characterization of Helichrysum italicum (Roth) G.Don subsp. italicum (Asteraceae) from Montenegro: phytochemical screening, chemotaxonomy, and antioxidant properties. Chem Biodivers. 2015;12(3):419-431.