Gabriel Alfonso Gutiérrez-Rebolledo

Hepatoprotective properties of oleanolic and ursolic acids in antitubercular drug-induced liver damage.

OBJECTIVEnTo estimate to what extent the mixture of ursolic acid and oleanolic acid, in addition to the antitubercular standard regime, affects the hepatotoxicity profile.nnnMETHODSnLiver injury was induced in male BALB/c mice by administering, per os and daily for 11 weeks, a combination of anti-Tubercular (anti-TB) agents Rifampicin (10xa0mg/kg), Isoniazid (10xa0mg/kg), and Pyrazinamide (30xa0mg/kg). The ursolic acid and oleanolic acid mixture at doses of 100 or 200xa0μg/mouse/day was subcutaneously injected throughout the entire study period (11xa0weeks). Biochemical and hematological analysis was supplemented by liver histological examination.nnnRESULTSnAnimals treated with the mixture of triterpenic acids exhibited significantly decreased aspartate transaminase and alanine aminotransferase levels and amelioration of the histopathological alterations produced by the anti-TB drugs.nnnCONCLUSIONSnThe triterpene mixture was able to prevent the steatosis induced by the anti-TB drugs.

Anti-inflammatory and toxicological evaluation of Moussonia deppeana (Schldl. & Cham) Hanst and Verbascoside as a main active metabolite.

ETHNOPHARMACOLOGICAL RELEVANCEnMoussonia deppeana, known as Tlachichinole, is a Mexican medicinal plant used for treatment of inflammatory diseases, influenza, diarrhea, gastrointestinal disorders and arthritis.nnnAIM OF THE STUDYnIn this paper the antioxidant and anti-inflammatory activities as well as the acute and sub-acute toxicological effects were evaluated for the ethanolic extract from aerial parts of M. deppeana, also its phytochemical analysis is described.nnnMATERIALS AND METHODSnPhytochemical analysis and compound isolation were performed with thin layer chromatography. The chemical identification of the main compound was performed by (1)H NMR (COSY, NOESY, HSQC and HMBC) spectra. In vitro antioxidant capacity and total phenolic content for the ethanolic extract and its primary fractions was determined by DPPH and Folin-Ciocalteu reagent. Acute and subacute toxicity tests were evaluated on Balb/C mice. Finally acute anti-inflammatory evaluation was tested for a local (TPA) and systemic (carrageenan) murine model.nnnRESULTSnThe main compound isolated from the ethanolic extract of M. deppeana was Verbascoside, which was isolated from F3 and was identified by (1)H NMR and COSY data. Furthermore oleanolic and ursolic acids were isolated from primary fractions F1 and F2. Ethanolic extract showed IC50 = 6.71mg/mL for DPPH test and 664.12µg QE/mL for the total phenolic content. The LD50 value was >2g/kg by i.g. route in male and female mice. Sub-acute administration (28 days) of the ethanolic extract (1g/kg) did not cause lethality or alter any hematological and biochemical parameters, in addition, histological analysis of the major organs exhibited no structural changes. Anti-inflammatory activity of the ethanolic extract showed an ED50 = 1.5mg/ear and 450mg/kg for TPA and carrageenan test, respectively. Primary fractions generated moderate local and systemic anti-inflammatory activity.nnnCONCLUSIONnThe ethanolic extract from the aerial parts of M. deppeana did not cause any lethality or adverse effect in either of the acute and sub-acute toxicity tests. This exhibited an important local and systemic anti-inflammatory activity and also moderate antioxidant capacity. Moreover, the primary fraction F2 was more active for the TPA model while the primary fraction F3 was most active in the carrageenan model in vivo. The main compound isolated from F3 was verbascoside; on the other hand also ursolic and oleanolic acids were isolated from F1 and F2.

Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review

Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and PubMed.

Medicinal Plants, an Important Reserve of Antimycobacterial and Antitubercular Drugs: An Update

Background: Tuberculosis is a global and serious Public Health problem due to the increase of multidrugresistant and extensively drug-resistant cases; as a result, diverse research groups worldwide are focusing their efforts on finding novel antituberculous agents that can provide greater effectiveness, less toxicity and having a specific mechanism of action, possibly being coadjuvants in the treatments currently prescribed. Methods: The present review covers the literature published concerning secondary metabolites of those Mexican medicinal plants and secondary metabolites isolated from them showing in vitro antimycobacterial activity with MIC <50 μg/mL against sensitive and MDR M. tuberculosis strains as well as against NTM strains. The review also includes a special section for those natural compounds or plant extracts with antitubercular activity evaluated an in vivo experimental tuberculosis model. Results: Some pure compounds with MIC<25 μg/mL are: 2-oxo-14-(3´,4´-methylenedioxyphenyl) tetradecane, 2- oxo-16-(3´,4´-methylenedioxyphenyl)hexadecane, 5,6-dehydro-7,8-dihydro methysticin, cepharanone B and piperolactam A (from Piper sanctum), suberosin (from Arracacia tolucensis) and leubethanol (from Leucophyllum frutescens). In addition, (-)-licarin A (from Aristolochia taliscana) was active against M. tuberculosis H37Rv, 12 MDR M. tuberculosis clinical isolates and four non-tuberculous mycobacteria. On the other hand, the antitubercular activity of (-)-licarin A, ursolic acid and oleanolic acid has been determined in a TB murine experimental in vivo model; (-)-licarin A reduces the bacterial lung load and the percentage of pneumonia in animals infected with M. tuberculosis H37Rv and MDR M. tuberculosis. The mixture of ursolic and oleanolic acids showed a significant reduction of bacterial loads and pneumonia in animals infected with M. tuberculosis H37Rv and MDR M. tuberculosis. Conclusion: Since (-)-licarin A, ursolic acid and oleanolic acid have been evaluated as antitubercular compounds, these metabolites are candidates proposed feasible to be proposed for development of antituberculosis drugs.

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 plants 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.

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceral-type leishmaniasis are recorded and 60000 persons died from the disease. In Mexico, cutaneous leishmaniasis is known as chicleros ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major, while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC50xa0≤xa030xa0μg/mL or μM have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5xa0mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

Anti-inflammatory evaluation and acute toxicity of three food supplements that contain Moussonia deppeana

OBJECTIVEnTo identify the anti-inflammatory activity through two murine models and in the median Lethal Dose (LD50) of three dietary supplements that contain Moussonia deppeana.nnnMETHODSnThe anti-inflammatory activity of three dietary supplements (Cicatrisan/Gastricus®, Gastinol®, and Gastrovita®) EtOH extracts was evaluated by TPA and by carrageenan murine models; also, median Lethal Dose (LD50) was determined. Verbascoside was quantified by High-Performance Liquid Chromatography. β-sitosterol, stigmasterol and the mixture of ursolic and oleanolic acids were identified in all supplements by TLC; however, none of these dietary supplements contain verbascoside.nnnRESULTSnFor the TPA model, Cicatrisan/Gastricus® generated a notable effect with 38.24% inhibition. While in the carrageenan model, it also exhibited noteworthy anti-inflammatory activity of ear edema with 66.39% of paw edema inhibition at 150xa0mg/kg, followed by Gastinol® and Gastrovita® with ≈50% at 300xa0mg/kg. Finally, LD50 was >2xa0g/kg for all supplements, when was administered intragastrically and Body Weight (BW) gain in mice was not altered after 14 days.nnnCONCLUSIONSnOf the three food supplements containing M.xa0deppeana, only the EtOH extract from Cicatrisan/Gastricus® formulation (tablets) showed significant anti-inflammatory activity in both experimental models and the LD50 was >2xa0g/kg.