Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice.

The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of MFN1, MFN2, DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, NLRP3, IL-18, IL-1ß) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including NGF, PSD95and PSD93 and BDNF in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.

Carnosine ameliorates age-related dementia via improving mitochondrial dysfunction in SAMP8 mice.

Dementia is a kind of age-related neurodegenerative disease. Carnosine, an endogenous dipeptide consisting of ß-alanine and l-histidine, has been shown to have neuroprotective effects. However, the exact mechanism is still obscure. In this study, senescence-accelerated mouse prone 8 (SAMP8) mice, an age-related animal model, were used. Carnosine (100 and 200 mg kg-1 day-1) was orally administered to the mice once daily for six weeks. Behavioral tests, western blotting, and detection kits were used to evaluate the potential effects of carnosine on SAMP8 mice. Open-field and new object recognition experiments have shown that carnosine improved cognitive deficits in SAMP8 mice. Carnosine decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), increased the activity of superoxide dismutase (SOD) and the level of adenosine triphosphate (ATP) in SAMP8 mice. Concomitantly, western blotting results proved that carnosine increased the protein expressions of Mitofusin-1, Mitofusin-2, and Bcl-2 and reduced the protein expressions of P-Drp1, Bax, cleaved Caspase-3 and NLRP3 inflammasomes in the hippocampus of SAMP8 mice. The present data provided evidence that carnosine might improve cognitive impairment in SAMP8 mice through modulating mitochondrial dysfunction.

Ligustilide improves aging-induced memory deficit by regulating mitochondrial related inflammation in SAMP8 mice.

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The main active component in Angelica sinensis, ligustilide, has been reported to have the protective effect on AD. Whether ligustilide could protect against age-induced dementia is still unknown. In this study, we used an aging model, SAMP8 mice to investigate the neuroprotective effect of ligustilide. The behavioral tests (Morris water maze, object recognition task, open field test and elevated plus maze) results showed that ligustilide could improve the memory deficit in SAMP8 mice. For mechanism study, we found that the protein level of P-Drp1 (fission) was decreased and the levels of Mfn1 and Mfn2 (fusion) were increased after ligustilide treatment in animals and cells. Ligustilide increased P-AMPK and ATP levels. Malondialdehyde and superoxide dismutase activity results indicated that ligustilide exerts antioxidant effects by reducing the level of oxidative stress markers. In addition, ligustilide improved neural function and alieved apoptosis and neuroinflammation. These findings have shown that ligustilide treatment improves mitochondrial function in SAMP8 mice, and improves memory loss.

Sodium tanshinone IIA sulfonate protects against Aß1-42-induced cellular toxicity by modulating Aß-degrading enzymes in HT22 cells.

ß-Amyloid (Aß) plays an important role in the pathogenesis of Alzheimer's disease (AD). However, there is still no effective Aß-targeting drugs for AD treatment. In this study, we explored the effect and mechanism of Sodium Tanshinone IIA Sulfonate (STS) on AD. Aß-treated HT22 cells, an immortalized mouse hippocampal neuronal cell line, were employed. Different dosages of STS (0.1, 1 and 10 µM) were selected. STS improved cell viability and protected against Aß-induced apoptosis in a dose-dependent manner. Furthermore, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were decreased, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased after STS treatment. STS decreased the levels of phosphorylate PKR-like (p-PERK), phosphorylate eukaryotic initiation factor 2 (p-eIF2α), phosphorylate inositol-requiring enzyme (p-IRE1α), X-box binding protein 1 (XBP1) and binding immunoglobulin heavy chain protein (Bip), while increased protein disulfide isomerase (PDI) levels in Aß-treated HT22 cells. In addition, the levels of insulin degrading enzymes (IDE) and Nepterrilysin (NEP) (or call it CD10) were significantly increased after STS treatment. Taken together, these results indicated that STS might be effective in treating AD via increasing the levels of Aß-degrading enzymes.