Investigation Of Icariin Mediated Anti-Ageing Effects On SAMP8 Mouse

Objective: To investigate the effect of icariin(ICA) on the senescent diverse organs of senescence accelerated mouse prone 8(SAMP8), and explore the potential mechanism.Methods: Eighty-four male SAMP8 mice and senescence accelerated mouse resistant 1(SAMR1) mice were randomly divided into 7 groups: 3 and 8 months SAMR1 as blank control, 3 and 8 months SAMP8 as model control, ICA low-, medium- and high-dose groups. SAMP8 mice were administered with ICA at the dose of 20, 40 and 80 mg/kg since 5 months age, once per day for 3 months. SAMP8 and SAMR1 control mice were given equal volume of distilled water.(1) Morris water maze was used to test the learning and memory ability. β-galactosidase staining was performed to specifically label aging brain tissue. Nissl staining was performed to examine neuronal morphology and nissl bodies in hippocampus CA1 region. Transmission electron microscope was performed to observe ultrastructure and autophagosome in hippocampus neurons. And the protein expression of LC3 B and p62 in cerebral and hippocampus was determined by Western blot.(2) β-galactosidase staining kit was also used to label senescent organs of liver and kidney. Biochemical analysis assays were used to determine the content of malondialdehyde(MDA), and the activities of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD) in the liver, kidney and thymus.Results:(1) Compared with the same age SAMR1 mice, the 8 months SAMP8 mice displayed significantly longer escape latency and shorter time spending in the platform region. The number of blue particles was significantly increased as assayed by β-galactosidase staining and the number of nissl bodies as well as normal neurons were decreased in the brain of 8-month SAMP8 mice compared to the same age SAMR1 mice. The results of transmission electron microscope showed that the mitochondria and endoplasmic reticulum were expanded; the number of autophagosomes were increased in 8-month SAMP8 mice. The protein expression of LC3 B and p62 in cerebral and hippocampus was significantly increased in 8-month SAMP8 mice. Administration with ICA 3 months, significantly improved the spatial learning and memory function of 8 months SAMP8 mice, accompanied by a decrease inthe senescence of brainand increase in the number nissl bodies and normal neurons. Further, it was found that the ultrastructure of neuron was improved, and the protein expression of LC3 B and p62 was significantly decreased in cerebral and hippocampus of SAMP8 mice when administrated with ICA for 3 months.(2) Compared with the same age SAMR1 mice, the number of blue particles was significantly increased in SAMP8 mice as detected by β-galactosidase staining, and the content of MDA in liver and kidney was significantly increased in 8-month SAMP8 mice, the activities of GSH-Px and SOD were dramatically decreased in liver, kidney and thymus of 8-month SAMP8 mice, all of which were reversed by administration with ICA for 3 months.Conclusion: ICA possesses the ability of delaying senescence of brain, liver, kidney and thymus in SAMP8 mice, which may be mediated through regulation of autophagy and anti-oxidation.