ABSTRACT
Although salidroside and salidroside-like compounds are considered as most critical constitutes needed and responsible for multiple therapeutic benefits of Rhodiola rosea L., including anti-aging, direct demonstration regarding the role of salidroside in anti-aging process is still deficient. In this study, we selected the H(2)O(2)-induced premature senescence model in human fetal lung diploid fibroblasts to investigate the protection of salidroside against aging in vitro and associated molecular mechanisms. We found that salidroside considerably reversed senescence-like phenotypes in the oxidant challenged model, including alterations of morphology, cell cycle, SA-ß-gal staining, DNA damage, as well as related molecules expression such as p53, p21 and p16. The protection occurred in a dose-dependent manner, with 5µM offering best efficacy. The proposed antioxidant property of the compound was confirmed in this cellular system, and thus at least partially accounted for the protection of the compound against premature senescence. Similar protection of salidroside against replicative senescence was observed as well. Interestingly, the regulation of senescence-related molecules by salidroside involved ROS-irrelevant mechanisms in both models. This finding presents salidroside as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.
Subject(s)
Aging, Premature/prevention & control , Antioxidants/pharmacology , Cellular Senescence/drug effects , Cytoprotection , Glucosides/pharmacology , Hydrogen Peroxide/antagonists & inhibitors , Phenols/pharmacology , Aging, Premature/pathology , Antioxidants/chemistry , Biomarkers/metabolism , Cell Cycle/drug effects , Cell Line , DNA Damage/drug effects , Fibroblasts/drug effects , Glucosides/chemistry , Humans , Hydrogen Peroxide/toxicity , Oxidative Stress/drug effects , Phenols/chemistry , Proteins/metabolism , Rhodiola/chemistry , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVE: To investigate the protective effects of putative AGEs (advanced glycation endproducts) inhibitor salidroside against aging in an accelerated mouse aging model induced by D-galactose. METHODS: A group of 5-month-old C57BL/6J mice were treated daily with D-galactose, D-galactose combined with salidroside, salidroside alone, and control buffer for 8 weeks. At the end of the treatment, serum AGEs levels, neurological activities, expression of glial fibrillary acidic protein (GFAP) and neurotrophin-3 (NT-3) in the cerebral cortex, as well as lymphocyte proliferation and IL-2 production were determined. RESULTS: D-galactose induced mouse aging model was developed as described before. As expected, salidroside blocked D-galactose induced increase of serum AGEs levels. It also reversed D-galactose induced aging effects in neural and immune system, as evidenced by improving motor activity, increasing memory latency time, and enhancing lymphocyte mitogenesis and interleukin-2 (IL-2) production. Furthermore, elevated expression of GFAP and NT-3 in the aged model mice was also reduced upon salidroside treatment. CONCLUSION: Salidroside inhibits AGEs formation in vivo, which at least partially contributes to its anti-aging effect in D-galactose induced aging model.
Subject(s)
Aging, Premature/prevention & control , Drugs, Chinese Herbal/therapeutic use , Glucosides/therapeutic use , Phenols/therapeutic use , Aging, Premature/blood , Aging, Premature/chemically induced , Animals , Cerebral Cortex/metabolism , Drugs, Chinese Herbal/pharmacology , Galactose , Glial Fibrillary Acidic Protein , Glucosides/pharmacology , Glycation End Products, Advanced/blood , Interleukin-2/metabolism , Memory/drug effects , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Nerve Growth Factors/metabolism , Nerve Tissue Proteins/metabolism , Phenols/pharmacology , Spleen/drug effects , Spleen/immunology , T-Lymphocytes/drug effectsABSTRACT
OBJECTIVE: To study whether Lycium barbarum glycopeptide 3 (LBGP3) affects T cell apoptosis in aged mice. METHODS: LBGP3 was purified with DEAE cellulose and Sephadex columns. Apoptotic "sub-G1 peak" was detected by flow cytometry and DNA ladder was resolved by agarose gel electrophoresis. Levels of IFN-gamma and IL-10 were measured with specific kits and mRNA expression was detected by RT-PCR. Apoptosis-related proteins of FLIP, FasL, and Bcl-2 were determined by Western blotting. RESULTS: LBGP3 was purified from Fructus Lycii water extracts and identified as a 41 kD glycopeptide. Treatment with 200 microg/mL LBGP3 increased the apoptotic rate of T cells from aged mice and showed a similar DNA ladder pattern to that in young T cells. The reversal of apoptotic resistance was involved in down-regulating the expression of Bcl-2 and FLIP, and up-regulating the expression of FasL. CONCLUSION: Lycium barbarum glycopeptide 3 reverses apoptotic resistance of aged T cells by modulating the expression of apoptosis-related molecules.
