Schisandra chinensis (Turcz.) Baill is produced mainly in northeast China, Korea and Japan. Its fruit has been used in food as a nutritional and functional ingredient for centuries. Polysaccharide is an important chemical component in Schisandra. Previous studies have shown that Schisandra polysaccharide (SCP) could be used to improve cognitive function clinically and treat age-related neurodegenerative disorders. In this study, a urinary metabolomics method based on ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was established to investigate the change of endogenous metabolites in an amyloid β-protein (Aβ) 25–35-induced Alzheimer's disease (AD) rat model. Meanwhile, levels of 9 neurotransmitters were evaluated with ultrahigh-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-TQ-MS) to explore the therapeutic mechanisms of SCP on the AD rat model. Additionally, the synthesis of phosphorylated tau protein (p-tau), acetylcholinesterase (AchE) activity and oxidative damage in the brain of the AD rats were assessed using glycogen synthase kinase-3β (GSK3β), AchE and antioxidant assays, NOS (nitric oxide synthase) and SOD (superoxide dismutase), respectively. The results indicated that the AD model was established successfully and the inducement of Aβ25–35 caused the phosphorylation of tau protein and the deposition of Aβ. In the AD model rats, the levels of AchE, GSK-3β and NOS were significantly elevated and SOD activity was reduced. In the hippocampus of the model rats, the contents of γ-aminobutyric acid, acetylcholine, glycine, norepinephrine, taurine, serotonin and dopamine were significantly decreased and the contents of glutamate and aspartic acid were increased significantly. However, SCP could reduce the degree of phosphorylation of tau protein, the deposition of Aβ and oxidative damage and reverse these changes of neurotransmitters in the AD rats. In a metabolomics study, a total of 38 metabolites were finally identified as potential biomarkers of AD and all of them had a significant recovery compared with the AD model after SCP administration. Metabolomics studies have shown that SCP plays a role in protecting the central nervous system, regulating intestinal microbial metabolism, regulating energy metabolism, and promoting antioxidant effects by regulating the levels of endogenous metabolites in related pathways. This is first report of the use of urine metabolomics combined with the evaluation of 9 neurotransmitter levels to investigate the mechanism of SCP on the treatment of AD.

As a well-known traditional Chinese medicine and functional food, Schisandra chinensis (S. chinensis) has been proved to possess excellent neuroprotective effects, and particularly the role of the polysaccharide fraction in neuroprotection has been increasingly emphasized. The aim of this study was to investigate the therapeutic effects and potential mechanism of action of the homogeneous polysaccharide SCP2, isolated and purified from S. chinensis polysaccharide (SCP), on Alzheimer's disease (AD) rats based on a holistic metabolomics approach in serum and urine. The results of the pharmacodynamics study showed that SCP2 significantly improved Aβ_25–35-induced cognitive dysfunction, improved oxidative damage and reduced Aβ deposition in the hippocampus. The holistic metabolomics results of serum and urine showed that the intervention with SCP2 significantly reversed the metabolic profile disorder in AD rats. A total of 40 metabolites (21 serum metabolites and 19 urine metabolites) were identified, which were mainly involved in linoleic acid metabolism, alpha-linolenic acid metabolism and arachidonic acid metabolism. The results obtained in this study will provide new insights into the mechanisms of SCP2 in the treatment of AD and provide a basis for the subsequent structure–activity studies of SCP2.

The causal effects of moderate alcohol consumption on cardiovascular diseases (CVDs) are continuously debated, especially on coronary artery disease (CAD). We aimed to explore the causal associations of alcohol consumption with CVDs and all-cause mortality among Chinese males. A prospective cohort study was conducted in 40,386 Chinese males, with 17,676 being genotyped for the rs671 variant in the aldehyde dehydrogenase 2 (ALDH2) gene. A Cox proportional hazards model was conducted to estimate the effects of self-reported alcohol consumption. Mendelian randomization (MR) analysis was performed to explore the causality using rs671 as an instrumental variable. During the follow-up of 303,353 person-years, 2406 incident CVDs and 3195 all-cause mortalities were identified. J-shaped associations of self-reported alcohol consumption with incident CVD and all-cause mortality were observed, showing decreased risks for light (≤25 g/d) and moderate drinkers (25−≤60 g/d). However, MR analyses revealed a linear association of genetically predicted alcohol consumption with the incident CVD (P-trend = 0.02), including both CAD (P-trend = 0.03) and stroke (P-trend = 0.02). The HRs (95% CIs) for incident CVD across increasing tertiles of genetically predicted alcohol consumption were 1 (reference), 1.18 (1.01, 1.38), and 1.22 (1.03, 1.46). After excluding heavy drinkers, the risk of incident CVD and all-cause mortality was increased by 27% and 20% per standard drink increment of genetically predicted alcohol consumption, respectively. Our analyses extend the evidence of the harmful effect of alcohol consumption to total CVD (including CAD) and all-cause mortality, highlighting the potential health benefits of lowering alcohol consumption, even among light-to-moderate male drinkers.