RESUMO
This study aimed to investigate the effect and possible mechanism of carnosic acid (CA) on delaying aging. The effects of CA on senescence-related β-galactosidase (SA-β-Gal) activity and expressions of p53, p21 and p16 were evaluated by an oxidative challenge induced premature 2BS cell senescence model. Meanwhile, the animal experiment was approved by the Ethics Committee of Zhejiang Hospital. Male C57 BL/6J mice were injected with 100 mg·kg-1·d-1 D-galactose (D-gal) for 8 weeks to establish an aging model in vivo, and CA at 5 and 10 mg·kg-1·d-1 were given ig administration at the same time. Morris water maze test was used to test the spatial memory ability. Then the serum and tissue samples were collected for the detections of malondialdehyde (MDA), total superoxide dismutase (T-SOD), interleukin-6 (IL-6), tumor necrosis factor α (TNFα) and advanced glycation end products (AGEs) as well as the protein expression of p53, p21 and p16 in hippocampus of brain. The results showed that H2O2 induced increment of SA-β-Gal activity (95%) was prevented by CA treatment (35%) and the enhanced protein expressions of p53, p21 and p16 in H2O2 exposed 2BS cells were alleviated by CA treatment, suggesting a potent protective role of CA against premature senescence induced by oxidative challenge. For in vivo study, D-gal induced declined spatial memory ability was partly reversed by CA administration. Besides, the serum and cerebral levels of MDA, IL-6, TNFα and AGEs were attenuated by CA treatment when compared to those in model mice. And the protein expressions of p53, p21 and p16 in mice hippocampus were suppressed by CA in D-gal treated mice. Taken together, our results showed that CA protects premature senescence induced by oxidative stress and D-gal, which is related to its antioxidative, antiinflammatory roles and inhibition on non-enzymatic glycosylation.
RESUMO
This study was designed to investigate the microRNA expression profile in human embryonic lung fibroblast 2BS cells upon salidroside (SAL) treatment, and predict the target genes of miRNAs and related pathways delaying cellular senescence. Samples were divided into three groups: young control (28 PD), old control (50 PD), and old+SAL (50 PD with SAL), RNA from three groups was used for miRNA microarray analysis. In late PD cells, 43 miRNAs were found significantly changed relatively to those in young cells, and 58 miRNAs were regulated by SAL. The miRNAs including hsa-let-7c, hsa-let-7e and hsa-mir-3620 were significantly down-regulated in late PD cells which could be reversed by SAL treatment. However, hsa-mir-411, hsa-mir-24-2-5p and hsa-mir-485-3p exhibited an opposite trend. Gene Ontology and Pathway analysis revealed that target genes were significantly enriched in 31 GO and 11 pathways. The microarray data was further validated with qRT-PCR. This research provides new clues regarding the underlying mechanisms of SAL on cellular senescence through miRNAs regulation.
