RESUMEN
Non-coding RNAs are involved with maintenance and regulation of physiological mechanisms and are involved in pathological processes, such as cancer. Among the small ncRNAs, miRNAs are the most explored in tumorigenesis, metastasis development, and resistance to chemotherapy. These small molecules of ~ 22 nucleotides are modulated during early renal development, involved in the regulation of gene expression and Wilms' tumor progression. Wilms' tumors are embryonic tumors with few mutations and complex epigenetic dysregulation. In recent years, the small ncRNAs have been explored as potentially related both in physiological development and in the tumorigenesis of several types of cancer. Besides, genes regulated by miRNAs are related to biological pathways as PI3K, Wnt, TGF-ß, and Hippo signaling pathways, among others, which may be involved with the underlying mechanisms of resistance to chemotherapy, and in this way, it has emerged as potential targets for cancer therapies, including for Wilms' tumors.
Asunto(s)
Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , ARN no Traducido/genética , Tumor de Wilms/etiología , Susceptibilidad a Enfermedades , Resistencia a Antineoplásicos , Predisposición Genética a la Enfermedad , Humanos , MicroARNs/genética , Interferencia de ARN , ARN Mensajero/genética , Transducción de Señal , Tumor de Wilms/diagnóstico , Tumor de Wilms/metabolismo , Tumor de Wilms/terapiaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The species Sparattosperma leucanthum (Vell.) K. Schum is used in Brazilian folk medicine to treat rheumatism, throat ulcers, stomatitis, syphilis, bladder stones and as blood cleanser. The aim of this study was to evaluate the potential, in vitro and in vivo, of the extracts of leaves from Sparattosperma leucanthum to treat hyperuricemia and inflammation in the gouty arthritis model. MATERIALS AND METHODS: Ethyl acetate extract (SLE), methanolic extract (SLM) and aqueous extract (SLW) were evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity and liver xanthine oxidase (XOD) inhibition. Anti-inflammatory activity was also investigated on MSU crystal-induced paw edema model. RESULTS: Sparattosperma leucanthum crude extracts showed expressive results on urate-lowering activity in blood. SLW at the dose of 125 mg/kg has proved to be active in reducing hyperuricemia and was capable to inhibit the hepatic xanthine oxidase enzyme (XOD). SLM showed anti-hyperuricemic activity on all doses tested; however, this extract showed activity on the XOD only at the dose of 500 mg/kg. SLE, at the three evaluated doses, has proved to be active in reducing hyperuricemia in vivo and was able to inhibit XO activity in vitro at the concentration of 100 µg/mL. This extract was also able to inhibit XOD activity in vivo at the doses of 250 mg/kg and 500 mg/kg. SLE (125 and 250 mg/kg) and SLW (500 mg/kg) showed significant anti-inflammatory activity on monosodium urate crystal-induced paw edema model. CONCLUSIONS: The ethyl acetate, methanolic and aqueous extracts of Sparattosperma leucanthum showed significant results on evaluated models and therefore may be important agents for the treatment of gouty arthritis and hyperuricemia.