RESUMEN
Schistosomiasis is a disease caused by parasites of the genus Schistosoma, currently affecting more than 200 million people. Among the various species of this parasite that infect humans, S. mansoni is the most common. Pharmacological treatment is limited to the use of a single drug, praziquantel (PZQ), despite reports of parasite resistance and low efficacy. It is therefore necessary to investigate new potential schistosomicidal compounds. In this study, we tested the efficacy of epiisopilosine (EPIIS) in a murine model of schistosomiasis. A single dose of EPIIS (100 or 400 mg/kg) administered orally to mice infected with adult S. mansoni resulted in reduced worm burden and egg production. The treatment with the lower dose of EPIIS (100 mg/kg) significantly reduced total worm burden by 60.61% (P < 0.001), as well as decreasing hepatosplenomegaly and egg excretion. Scanning electron microscopy revealed morphological changes in the worm tegument after treatment. Despite good activity of EPIIS in adult S. mansoni, oral treatment with single dose of EPIIS 100 mg/kg had only moderate effects in mice infected with juvenile S. mansoni. In addition, we performed cytotoxicity and toxicological studies with EPIIS and found no in vitro cytotoxicity (in HaCaT, and NIH-3T3 cells) at a concentration of 512 µg/mL. We also performed in silico analysis of toxicological properties and showed that EPIIS had low predicted toxicity. To confirm this, we investigated systemic acute toxicity in vivo by orally administering a 2000 mg/kg dose to Swiss mice. Treated mice showed no significant changes in hematological, biochemical, or histological parameters compared to non-treated animals. Epiisopilosine showed potential as a schistosomicidal drug: it did not cause acute toxicity and it displayed an acceptable safety profile in the animal model.
Asunto(s)
Alcaloides/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomiasis mansoni/tratamiento farmacológico , Animales , Línea Celular , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Células 3T3 NIH , Recuento de Huevos de Parásitos/métodos , Praziquantel/farmacología , Esquistosomiasis mansoni/parasitología , Esquistosomicidas/farmacologíaRESUMEN
Chlorogenic acid is a natural potent antioxidant. It can be used in cosmetics formulations, but for this purpose its photochemical stability should be determined to ensure that the compound will not be degraded after UV radiation exposure. To evaluate this possibility, the concentration of a chlorogenic acid solution was determined by HPLC before and after UVA and UVB irradiation.The results indicate that chlorogenic acid is not degraded under UVA or UVB irradiation.
Asunto(s)
Ácido Clorogénico/química , Ácido Clorogénico/efectos de la radiación , Rayos Ultravioleta , Antioxidantes/química , Antioxidantes/efectos de la radiación , Estabilidad de Medicamentos , Protectores Solares/química , Protectores Solares/efectos de la radiaciónRESUMEN
Exposure to UV radiation up-regulates the synthesis of matrix metalloproteinases (MMPs), a group of matrix-degrading enzymes. MMPs are regarded as promising therapeutic targets and the development of effective inhibitors is an important research focus. The plant Pothomorphe umbellata has been shown to exert a potent antioxidant activity on the skin and to delay the onset and reduce the incidence of UVB-induced chronic skin damage. The aim of the present study was to determine the effect of P. umbellata ethanolic root extract on MMP-2 and MMP-9. The in vitro inhibition of MMP-2 and MMP-9 was measured by gelatin zymography in the presence of different concentrations of P. umbellata extract, as well as in the presence of its isolated active principle 4-nerolidylcatechol (4-NC). The inhibitory effect of the P. umbellata extract was stronger than that of 4-NC. Gelatin zymography and histological analysis revealed that P. umbellata was able to inhibit constitutive MMP-9 activity in vivo in mice sacrificed 2 h after UVB irradiation. The intensity of the MMP-2 band was unchanged. Our data contribute to the elucidation of the mechanism of prevention of photoaging by P. umbellata and may provide a rational basis for the use of this plant in prophylaxis against and treatment of skin cancer.
Asunto(s)
Inhibidores de la Metaloproteinasa de la Matriz , Piperaceae/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Protectores contra Radiación/farmacología , Piel/enzimología , Animales , Catecoles/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Gelatina/química , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Pelados , Fitoterapia/métodos , Extractos Vegetales/química , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/prevención & control , Factores de Tiempo , Rayos UltravioletaRESUMEN
Due to its antioxidant and photoprotective properties, Pothomorphe umbellata is a promising candidate for use in cosmetic and pharmaceutical formulations. These properties arise from the presence of 4-nerolidylcathecol (4-NC), a polyphenolic compound isolated from P. umbellata roots. This study investigates its photostability properties, as well as the chemical and the in vitro sun protection factor (SPF) of P. umbellata root extract in a gel formulation. A high performance liquid chromatography method was used to evaluate the chemical stability using 4-NC as marker at 5, 25 and 45 degrees C for 103 days. The photostability and the sun protection factor were analyzed by ultraviolet (UV) spectophotometry using samples irradiated with UVB lamp. No significant difference of the 4-NC concentration was found in formulations stored at 5 and 25 degrees C. All samples stored at 45 degrees C, however, showed degradation of gel structure. After 2h of UVB exposure, there was no change in the absorption profile of 4-NC. The sun protection factor of P. umbellata root extract gel to final concentration of 0.1% 4-NC was not expressive (SPF=3.35+/-0.02), suggesting the predominance of its antioxidant activity.
Asunto(s)
Piperaceae/química , Extractos Vegetales/química , Protectores Solares/química , Resinas Acrílicas , Catecoles/análisis , Estabilidad de Medicamentos , Geles , Fotoquímica , Extractos Vegetales/efectos de la radiación , Raíces de Plantas/química , Espectrofotometría , Protectores Solares/análisis , Protectores Solares/efectos de la radiación , Temperatura , Factores de Tiempo , Rayos UltravioletaRESUMEN
In this work we evaluated the influence of topical application of P. umbellata root extract gel, containing 0.1% of 4-nerolidylcathecol, on the antioxidant network in UV-induced oxidative damage in hairless mouse skin. The UV-irradiation had no influence on ascorbic acid levels or on the antioxidant enzyme (superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase) activities, but topical P. umbellata treatment protected alpha-tocopherol from being depleted after UV-irradiation. alpha-Tocopherol concentration decreased significantly (approximately 40%, P < 0.01) in the irradiated control groups, whereas in the P. umbellata-treated group, alpha-tocopherol was totally preserved (approximately 100%, P > 0.05). These data demonstrate that P. umbellata may be successfully used as a topical photoprotective agent.
Asunto(s)
Antioxidantes/metabolismo , Piperaceae/química , Extractos Vegetales/farmacología , Piel/efectos de la radiación , Rayos Ultravioleta , alfa-Tocoferol/metabolismo , Animales , Ratones , Ratones Pelados , Piel/enzimología , Piel/metabolismoRESUMEN
Antioxidants such as vitamins E and C are known to play a significant role in ameliorating or preventing oxidative damage to the skin. However, to provide a satisfactory protection they must first permeate the skin, which serves as a permeation barrier. In this study we evaluated the influence of three different formulations (gel, gel-emulsion and emulsion) on the percutaneous absorption of 4-nerolidylcathecol, an antioxidant compound isolated from Pothomorphe umbellata root extracts. Also, the absorption of the isolated 4-nerolidylcathecol was compared with its absorption when dried P. umbellata root ethanolic extract was incorporated into a gel formulation. The 'lag time method' was employed for the analysis of the in vitro permeation data. All formulations showed satisfactory percutaneous penetration with the 4-nerolidylcathecol-gel presenting a higher rate of penetration leading to higher dry drug levels in the tissue.