RESUMEN
Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.
Asunto(s)
Envejecimiento/efectos de los fármacos , Antioxidantes/uso terapéutico , Galactosa/farmacología , Naftalenos/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Sesquiterpenos/uso terapéutico , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/patología , Expresión Génica/efectos de los fármacos , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Ratones , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Memoria Espacial/efectos de los fármacosRESUMEN
BACKGROUND: Biological and pharmacological activities of dryocrassin ABBA, a phloroglucinol derivative extracted from Dryopteris crassirhizoma, have attracted attention. In this study, the apoptotic effect of dryocrassin ABBA on human hepatocellular carcinoma HepG2 cells was investigated. MATERIALS AND METHODS: We tested the effects of dryocrassin ABBA on HepG2 in vitro by MTT, flow cytometry, real-time PCR, and Western blotting. KM male mice were used to detect the effect of dryocrassin ABBA on H22 cells in vivo. RESULTS: Dryocrassin ABBA inhibited the growth of HepG2 cells in a concentration-dependent manner. After treatment with 25, 50, and 75 µg/mL dryocrassin ABBA, the cell viability was 68%, 60% and 49%, respectively. Dryocrassin ABBA was able to induce apoptosis, measured by propidium iodide (PI)/annexin V-FITC double staining. The results of real-time PCR and Western ting showed that dryocrassin ABBA up-regulated p53 and Bax expression and inhibited Bcl-2 expression which led to an activation of caspase-3 and caspase-7 in the cytosol, and then induction of cell apoptosis. In vivo experiments also showed that dryocrassin ABBA treatment significantly suppressed tumor growth, without major side effects. CONCLUSIONS: Overall, these findings provide evidence that dryocrassin ABBA may induce apoptosis in human hepatocellular carcinoma cells through a caspase-mediated mitochondrial pathway.
