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

Antimycobacterial neolignans isolated from Aristolochia taliscana

Tuberculosis (TB - Mycobacterium tuberculosis) is an ancient infectious disease that has appeared once again as a serious worldwide health problem and now comprises the second leading cause of death resulting from a single infection. The prevalence of multidrug resistance (MDR) TB is increasing and therapeutic options for treatment are not always accessible; in fact, some patients do not respond to the available drugs. Therefore, there is an urgent need to develop novel anti-TB agents. The aim of the present study was to screen extracts of Aristolochia taliscana, a plant used in traditional Mexican medicine to treat cough and snake bites, for antimycobacterial activity. The hexanic extract of A. taliscana was tested by microdilution alamar blue assay against Mycobacterium strains and bioguided fractionation led to the isolation of the neolignans licarin A, licarin B and eupomatenoid-7, all of which had antimycobacterial activity. Licarin A was the most active compound, with minimum inhibitory concentrations of 3.12-12.5 μg/mL against the following M. tuberculosis strains: H37Rv, four mono-resistant H37Rv variants and 12 clinical MDR isolates, as well as against five non-tuberculous mycobacteria (NTM) strains. In conclusion, licarin A represents a potentially active anti-TB agent to treat MDR M. tuberculosis and NTM strains

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model

Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world’s adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4′-trifluoromethylbenzylamino and 3′,4′-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs