RESUMEN
Chagas disease, caused by the protozoan Trypanosoma cruzi, is considered a public health problem. The current chemotherapy for this illness causes serious side effects and its use in the chronic phase of the disease is still controversial. In this regard, the investigation of novel therapeutic strategies remains a priority. The essential oils (EOs) from aromatic plants emerge as a promising source of bioactive compounds. In a previous work we reported the trypanocidal activity of the essential oils from the medicinal plants Lippia sidoides (LSEO) and Lippia origanoides (LOEO) against T. cruzi. Herein, we aimed to further investigate, in more details, the mode of action of LSEO and LOEO on the different developmental stages of this parasite. We showed that Lippia sidoides (LSEO) and Lippia origanoides (LOEO) induced a significant reduction in the percentage of macrophages infected by T. cruzi and in the number of intracellular parasites. Ultrastructural analysis showed that the treatment with both oils caused morphological changes consistent with loss of viability and cell death. The reduced staining with calcein and the increase in the proportion of HE-positive cells also demonstrated that LSEO and LOEO caused loss of parasite viability and membrane integrity. A considerable decrease in Rhodamine 123 and an increase in fluorescence intensity of MitoSox in LOEO were indicative of loss of mitochondrial potential and generation of reactive oxygen species, which ultimately lead to parasite death. Moreover, the optical tweezer analysis indicated that LOEO was more effective in reducing the motility of the epimastigotes. Taken together, our results demonstrated that the LSEO and LOEO are active against T. cruzi and constitute a promising drugs for the therapy of Chagas disease.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Aceites Volátiles/farmacología , Aceites de Plantas/farmacología , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Enfermedad de Chagas/parasitología , Enfermedad de Chagas/prevención & control , Lippia/química , Trypanosoma cruzi/ultraestructuraRESUMEN
This study aims to obtain mesocarp films of Orbignya sp. (MB) and carboxymethylcellulose (CMC) for application as a drug release matrix. Tannic acid (TA) was used as a standard drug. The films were evaluated by infrared, swelling power, TA release profile, bioactivity and in vitro cytotoxicity. Infrared results indicated absorption at 1.205 cm-1, which is characteristic of ester group from the incorporated tannin. The MB-CMC film had 449.15% swelling power, release of 71.01% of TA of the matrix after 24 h. Films showed scavenger activity of radicals DPPH (79.07 ± 1.71% to 82.17 ± 1.94%) and ABTS+ (82.20 ± 0.30% to 88.90 ± 1.05). The MB-CMC film also showed in vitro cytotoxicity on sarcoma-180 (91.86 ± 9.97%) and on promastigote forms of Leishmania major (100%). Polymers showed good compatibility in the mixture and the results suggest the films obtained are promising as drug release matrices.
Asunto(s)
Arecaceae/química , Carboximetilcelulosa de Sodio , Frutas/química , Leishmania major/crecimiento & desarrollo , Ensayo de Materiales , Membranas Artificiales , Taninos , Animales , Antiprotozoarios/química , Antiprotozoarios/farmacología , Carboximetilcelulosa de Sodio/química , Carboximetilcelulosa de Sodio/farmacología , Línea Celular Tumoral , Ratones , Taninos/química , Taninos/farmacologíaRESUMEN
The cashew nut releases a substance that is known as cashew nut shell liquid (CNSL). There are both natural (iCNSL) and technical (tCNSL) cashew nut shell liquids. This study used an Artemia salina bioassay to evaluate the toxic effects of iCNSL and tCNSL cashew nut shell liquids. It also evaluated the toxicity, cytotoxicity, and mutagenicity of CNSL and its effects on the damage induced by copper sulfate (CuSO4·5H2O) on the meristems' root of Allium cepa. Effects of the damage induced by CuSO4·5H2O were evaluated before (pre-), during (co-), and after (post-) treatments. The iCNSL contained 94.5% anacardic acid, and the tCNSL contained 91.3% cardanol. The liquids were toxic to A. salina. Toxicity, cytotoxicity, and mutagenicity were observed with iCNSL compared with the negative control. Similarly, iCNSL failed to inhibit the toxicity and cytotoxicity of CuSO4·5H2O. The tCNSL was not toxic, cytotoxic, or mutagenic in any of the concentrations. However, the lowest iCNSL concentrations and all of the tCNSL concentrations had preventive, antimutagenic, and reparative effects on micronuclei and on chromosomal aberrations in the A. cepa. Therefore, protective, modulating, and reparative effects may be observed in the A. cepa, depending on the concentration and type of CNSL used.
Asunto(s)
Anacardium/química , Antimutagênicos/farmacología , Artemia/efectos de los fármacos , Factores Biológicos/farmacología , Mutágenos/farmacología , Nueces/química , Cebollas/efectos de los fármacos , Ácidos Anacárdicos/farmacología , Animales , Bioensayo/métodos , Fenoles/farmacologíaRESUMEN
The Lippia origanoides H.B.K. ethanol extract (LOEE) and hexane (LOHEX), dichloromethane (LODCM), and ethyl acetate (LOEA) fractions were tested for their antimicrobial activity alone or in combination with antibiotics against a methicillin resistant Staphylococcus aureus (MRSA) strain. The natural products did not show antimicrobial activity against multidrug resistant strain at the clinically significant concentrations tested. However, a modulatory effect in the antibacterial activity of the neomycin and amikacin was verified when LOEE, LOHEX and LODCM were added to the growth medium at subinhibitory concentrations. A similar modulation was found when the natural products were changed for chlorpromazine, an inhibitor of bacterial efflux pumps, suggesting the involvement of resistance mediated by efflux system in the MRSA tested. The fractions LOHEX and LODCM showed a modulatory activity bigger than their majority compounds (carvacrol, thymol, and naringenin), indicating that this activity is not due to their majority compounds only, but it is probably due to a synergism between their chemical components. These results indicate that L. origanoides H.B.K. can be a source of phytochemicals able to modify the phenotype of resistance to aminoglycosides in MRSA.