Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation.

Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aß) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H2O2 and C57BL/6 mice with AD challenged with AlCl3 combined with D-galactose. Results showed that dioscin obviously increased cell viability and decreased reactive oxygen species (ROS) level in injured SH-SY5Y cells. In vivo, dioscin obviously improved the spatial learning and memory abilities as well as gait and interlimb coordination disorders of mice with AD. Moreover, dioscin distinctly restored the levels of malondialdehyde (MDA), superoxide dismutase (SOD), amyloid beta 42 (Aß42), acetylcholine (ACh) and acetylcholinesterase (AChE) of mice, and reversed the histopathological changes of brain tissue. Mechanism studies revealed that dioscin markedly down-regulated the expression levels of RAGE and NOX4. Subsequently, dioscin markedly up-regulated the expression levels of Nrf2 and HO-1 related to oxidative stress, and down-regulated the levels of p-NF-κB(p-p65)/NF-κB(p65), AP-1 and inflammatory factors involved in inflammatory pathway. RAGE siRNAs transfection further clarified that the pharmacological activity of dioscin in AD was achieved by regulating RAGE/NOX4 pathway. In conclusion, dioscin showed excellent anti-AD effect by adjusting RAGE/NOX4-mediated oxidative stress and inflammation, which provided the basis for the further research and development against AD.

Hengshun Aromatic Vinegar Improves Glycolipid Metabolism in Type 2 Diabetes Mellitus via Regulating PGC-1α/PGC-1ß Pathway.

Hengshun aromatic vinegar (HSAV), produced by typical solid-state or liquid-state fermentation techniques, is consumed worldwide as a food condiment. HSAV shows multiple bioactivities, but its activity in type 2 diabetes mellitus (T2DM) and possible mechanisms have not been reported. In this study, the effects of HSAV against T2DM were evaluated in insulin-induced HepG2 cells and high-fat diet (HFD) and streptozotocin (STZ) induced T2DM rats. Then, the mechanisms of HSAV against T2DM were explored by Real-time PCR, Western blot, immunofluorescence assays, siRNA transfection and gene overexpression experiments. Results indicated that HSAV significantly improved glucose consumption and reduced triglycerides (TG) contents in metabolic disordered HepG2 cells. Meanwhile, HSAV obviously alleviated general status, liver and kidney functions of T2DM rats, and decreased hyperglycemia and hyperlipidemia, improved insulin resistance, and reduced lipid accumulation in liver. Mechanism studies indicated that HSAV markedly down-regulated the expression of proliferator-activated receptor γ coactivator-1α (PGC-1α), then regulated peroxisome proliferators-activated receptor α (PPAR-α)/protein kinase B (AKT) signal pathway mediated gluconeogenesis and glycogen synthesis. Meanwhile, HSAV significantly up-regulated proliferator-activated receptor γ coactivator-1ß (PGC-1ß), and subsequently decreased sterol regulatory element binding protein-1c (SREBP-1c) pathway mediated lipogenesis. In conclusion, HSAV showed potent anti-T2DM activity in ameliorating dysfunction of glycolipid metabolism through regulating PGC-1α/PGC-1ß pathway, which has a certain application prospect as an effective diet supplement for T2DM therapy in the future.

Hepatoprotective Effect and Molecular Mechanisms of Hengshun Aromatic Vinegar on Non-Alcoholic Fatty Liver Disease.

Aromatic vinegar with abundant bioactive components can be used as a food additive to assist the treatment of various diseases. However, its effect on non-alcoholic fatty liver disease (NAFLD) is still unknown. The purpose of this study was to investigate the mechanism of Hengshun aromatic vinegar in preventing NAFLD in vivo and in vitro. Aromatic vinegar treatment was applied to rats fed with a high-fat diet (HFD) and HepG2 cells challenged with palmitic acid (PA). Our results showed that aromatic vinegar markedly improved cell viabilities and attenuated cell damage in vitro. The levels of TC, TG, FFA, AST, ALT, and malondialdehyde (MDA) in HFD-induced rats were significantly decreased by aromatic vinegar. Mechanism investigation revealed that aromatic vinegar markedly up-regulated the level of silent information regulator of transcription 1 (Sirt1), and thereby inhibited inflammation of the pathway through down-regulating the expressions of high mobility group box 1, toll-likereceptor-4, nuclear transcription factor-κB, tumor necrosis factor receptor-associated factor-6, and inflammatory factors. Aromatic vinegar simultaneously increased the expression of farnesoid X receptor and suppressed expressions of lipogenesis related proteins, including fatty acid synthase, acetyl-CoA carboxylase-1, sterol regulatory element binding transcription factor 1, and stearoyl-CoA desaturase-1. These results were further validated by knockdown of Sirt1 using siRNAs silencing in vitro. In conclusion, Hengshun aromatic vinegar showed protective effects against NAFLD by enhancing the activity of SIRT1 and thereby inhibiting lipogenesis and inflammation pathways, which is expected to become a new assistant strategy for NAFLD therapy in the future.