Additional compounds and the therapeutic potential of Cnidoscolus chayamansa (McVaugh) against hepatotoxicity induced by antitubercular drugs.

Previously non-isolated compounds (scopoletin and ß-D-Glucopyranoside, (1R)-O-isopropyl 6-O-(2,3,4-tri-O-acetyl-ß-D-xylopyranosyl)-2,3,4-triacetate) were isolated from an organic extract of the Cnidoscolus chayamansa stem. Also, lupeol acetate (main compound, 49.7 mg/g of dry extract) and scopoletin (0.19 mg/g of dry extract) were quantified by HPLC analysis from this organic extract. The protective activity of the C. chayamansa organic extract against hepatotoxicity induced by antitubercular drugs [Rifampicin (50 mg/kg), Isoniazid (50 mg/kg), and Pyrazinamide (100 mg/kg)] are reported. The extract was tested at 200 and 400 mg/kg in Balb/C mice during 85 days, using silymarin (2.5 mg/kg) as positive control. Liver damage was determined using biochemical parameters (AST, ALT, ALP, CHOL, HDL TG, Urea, and CREA), histological analysis, and evaluation of oxidative stress (SOD, CAT, Gpx, Lpx and POx). The extract at both doses favored body weight gain with respect to the anti-TB group; the dose of 200 mg/kg was better. Also, the extract at both doses decreased the values of transaminases (AST, ALT) enzymes (p < 0.05) vs. anti-TB group. In oxidative stress parameters, the SOD value was decreased, as were the levels of peroxidation of lipids and oxidative protein in the group with C. chayamansa extract at 200 and 400 mg/kg vs. the anti-TB group. Histological analyses from liver showed the absence of steatosis in the extract group at 400 mg/kg, and moderate steatosis in the silymarin and extract (at 200 mg/kg) groups with respect to anti-TB group, which demonstrated a steatosis. It should be noted that during the study period, none of the treated mice died. In conclusion, the CHCl3: MeOH extract of C. chayamansa has a hepatoprotective effect against hepatotoxicity induced by anti-TB drugs.

Hepatoprotective and Anti-Inflammatory Activities of the Cnidoscolus chayamansa (Mc Vaugh) Leaf Extract in Chronic Models.

Previous report described that CHCl3:MeOH extract of C. chayamansa leaves and pure compounds (moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone) showed important topical and systemic anti-inflammatory activity in acute model, as well as in vitro antimycobacterial and antiprotozoal activities. In this paper, we describe the in vivo hepatoprotective and anti-inflammatory effects of the CHCl3:MeOH extract in chronic model and the isolation of additional compounds (moretenone and lupeol acetate). The hepatoprotective activity was determined at 39 days using Balb/c mice with liver damage induced with an antitubercular drug (RIF/INH/PZA). The anti-inflammatory activity was evaluated in a chronic model induced with CFA and in two acute models (TPA and carrageenan). In addition, moretenone and lupeol acetate were isolated and identified by spectroscopic data. Lupeol acetate is a main compound present in fractions 14-42, and this fraction was the majority fraction from the extract; from this moretenone was obtained. In animals with liver damage, the extract at 200 and 400 mg/kg induced better body weight gain with respect to positive control (Silymarin); in addition, the mice that received the extract at 200 mg/kg and Silymarin exhibited slight steatosis; however, the animals' livers at 400 mg/kg did not show steatosis. The extract and fractions 14-42 showed a good anti-inflammatory activity by TPA model (DE50 = 1.58 and 1.48 mg/ear) and by carrageenan model (DE50 = 351.53 and 50.11 mg/kg). In the chronic inflammatory test, the extract at three doses revealed a similar effect to that of phenylbutazone, although the body weight gain was better in animals that received the extract at 900 mg/kg. Conclusion. The CHCl3:MeOH extract showed significant anti-inflammatory and good hepatoprotective effect on chronic models. The fraction containing moretenone and lupeol acetate as main compounds was more active than extract in both acute models of inflammation.

Antiprotozoal, antimycobacterial, and anti-inflammatory evaluation of Cnidoscolus chayamansa (Mc Vaugh) extract and the isolated compounds.

Cnidoscolus chayamansa is a medicinal and edible plant known as Chaya, is commonly used as an anti-inflammatory, antiprotozoal, antibacterial agent and as a remedy for respiratory illness, gastrointestinal disorders, and vaginal infections related with the inflammation process. In this paper, we describe the plant's phytochemical analysis and biological activities (antimycobacterial, antibacterial, antiprotozoal, and anti-inflammatory properties) of the CHCl3:MeOH (1:1) leaves extract and isolated compounds, as well as the acute and sub-acute toxic effects. Chemical identification of isolated compounds was performed by 1H- and 13C NMR spectra data. In vitro antibacterial and antimycobacterial activities were determined by disc diffusion and MABA assays, respectively; antiprotozoal test by means of the sub-culture test. Topical and systemic anti-inflammatory effects were tested by TPA and carrageenan assay on BALB/c mice. Moretenol, moretenyl acetate, kaempferol-3,7-dimethyl ether, and 5-hydroxy-7-3',4'-trimethoxyflavanone were the main compounds isolated. The CHCl3:MeOH extract showed antiprotozoal (IC50≤65.29µg/mL), antimycobacterial (MIC≤50µg/mL), and anti-inflammatory activities (ED50=1.66mg/ear and 467.73mg/kg), but was inactive against the bacterial strains tested. The LD50 for extract was >2g/kg. In the sub-acute toxicity test, the extract was administered at 1g/kg for 28days and did not cause lethality or any alteration in hematological and biochemical parameters; in addition, liver, kidney, and spleen histological analysis exhibited no structural changes. Moretenol and moretenyl acetate showed MIC=25µg/mL against Mycobacterium tuberculosis H37Rv and against four monoresistant strains of M. tuberculosis H37Rv. Both compounds exhibited moderate activity against Entamoeba histolytica and Giardia lamblia (IC50≤71.70µg/mL). Kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxy-flavanone were more active than the extract against E. histolytica and G. lamblia, showing IC50 ≤27.43µg/mL. As topical anti-inflammatory agents, moretenol and kaempferol-3,7-dimethyl ether were the most active compounds inhibiting the edema in 30.52 and 26.67%, respectively. Moretenol and moretenyl acetate showed significant antimycobacterial and antiprotozoal activities; in addition, important antiprotozoal effect was detected with kaempferol-3,7-dimethyl ether and 5-hydroxy-7-3',4'-trimethoxyflavanone. The extract and the terpenoids possess good anti-inflammatory activity. The extract did not produce lethality or adverse effects in acute and sub-acute tests.