Combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus ameliorates aluminum-induced Alzheimer's disease via reducing BACE1 expression.

Being the most common form of dementia, Alzheimer's disease (AD) has a series of modifiable risk factors, including metal ions represented by aluminium. Aluminium (Al) exhibits its neurotoxic effects, especially mainly by affecting amyloid-ß protein (Aß) aggregation and Tau hyperphosphorylation. As reported in our previous study, the combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus (AS) had a neuroprotective effect. This study aimed to evaluate the anti-AD effect of AS and the mechanism by which AS reduces the neurotoxic effect of Al. Firstly, we used aluminium-maltol (Al(mal)3) to construct a mouse model of AD and performed oral administration of AS, followed by behavioral experiments, and we collected the mouse brain for immunohistochemistry analysis. In vivo results showed that AS significantly improved Al-induced cognitive decline in mice, and reduced the levels of Aß1-42 and P-Tau in the brain, which further proved the anti-AD effect of AS. Then, in order to explore the mechanism by which AS reduced Aß1-42, Al-induced PC12 cells were used for the in vitro experiments. Compared with other ratios, the ratio of Alpinia Oxyphylla Fructus: Schisandra Chinensis Fructus (AO:SC) = 1:2 could better improve the cell viability and reduce the Aß1-42 level. According to western blot and quantitative real-time polymerase chain reaction (qPCR) results, AS ameliorated the pathological process by downregulating the expression of ß-secretase (BACE1), rather than by reducing the expression of amyloid precursor protein (APP) or Tau. These results suggest that AS ameliorated Al-induced AD by affecting the expression of BACE1 and reducing the level of Aß1-42, thereby exerting a neuroprotective effect. Combined with previous studies, this study shows that AS has potential for further research and development in AD treatment.

Chemical composition analysis of Schisandra chinensis fructus and its three processed products using UHPLC-Q-Orbitrap/MS-based metabolomics approach.

An ultra-high performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry (UHPLC-Q-Orbitrap/MS)-based metabolomics method was applied to investigate the chemome diversity of Schisandra chinensis fructus (SF) and its processed products, including vinegar-processed Schisandra (VS), wine-processed Schisandra (WS), and honey-processed Schisandra (HS). A clear classification among four Schisandra products was observed in the score plot of the partial least-squares discriminant analysis (PLS-DA) model, then 28 marker compounds were selected and identified. The content of most marker compounds in VS and WS was increased compared with that in SF, and the lowest content was observed in HS, then the high-performance liquid chromatography (HPLC) analysis was performed to confirm the change trends. These results suggested the chemical composition variation occurs in different Schisandra products, and the marker compounds selected in this study will be useful for the quality evaluation of Schisandra products.

Polysaccharide of Schisandra Chinensis Fructus ameliorates cognitive decline in a mouse model of Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Polysaccharides is an important ingredient of Schisandra Chinensis Fructus which often appears in ancient prescriptions for forgetfulness or dementia. AIM OF THE STUDY: The purpose of our study is to investigate the effects of polysaccharides of Schisandra Chinensis Fructus (SCP) on animal model of Alzheimer's disease (AD), which is a common disease of dementia, to elucidate the traditional medical theories with modern pharmacological methods and provide a reference for further clarifying its active mechanisms. MATERIALS AND METHODS: Hydrolysates of SCP were analyzed by HPLC. Y-maze, Morris water maze (MWM) were used for evaluating cognition processes of mice. Immunohistochemistry (IHC) was used to detect the deposition of Aß. The levels of cytokine expression including Tumor Necrosis Factor α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the hippocampus were detected by ELISA kits. Activation of astrocytes and microglia was assessed by immunofluorescence labeling GFAP and Iba-1. The phosphorylated state of various mitogen-activated protein kinase (MAPKs) signaling molecules (p38 MAPK, ERK 1/2, and JNK) and activation of nuclear factor κB (NF-κB) was studied by western blot. Histopathological changes were observed by H.E. straining. RESULTS: SCP could significantly improve the cognition and histopathological changes of AD mice, reduce the deposition of Aß, downregulate the expression of pro-inflammatory cytokines and the activation of glial cells in the hippocampus. Further, SCP decreased nuclear displacement of NF-κB and MAPKs phosphorylation. CONCLUSIONS: SCP could improve the cognition of mice, and it may play an anti-AD role by activating the NF-κB/MAPK pathway to alleviate neuroinflammation.

Schisandra chinensis Fructus and Its Active Ingredients as Promising Resources for the Treatment of Neurological Diseases.

Neurological diseases (NDs) are a leading cause of death worldwide and tend to mainly affect people under the age of 50. High rates of premature death and disability caused by NDs undoubtedly constrain societal development. However, effective therapeutic drugs and methods are very limited. Schisandra chinensis Fructus (SCF) is the dry ripe fruit of Schisandra chinensis (Turcz.) Baill, which has been used in traditional Chinese medicine for thousands of years. Recent research has indicated that SCF and its active ingredients show a protective role in NDs, including cerebrovascular diseases, neurodegenerative diseases, or depression. The key neuroprotective mechanisms of SCF and its active ingredients have been demonstrated to include antioxidation, suppression of apoptosis, anti-inflammation, regulation of neurotransmitters, and modulation of brain-derived neurotrophic factor (BDNF) related pathways. This paper summarizes studies of the role of SCF and its active ingredients in protecting against NDs, and highlights them as promising resources for future treatment. Furthermore, novel insights on the future challenges of SCF and its active ingredients are offered.

An integrated strategy using UPLC-QTOF-MSE and UPLC-QTOF-MRM (enhanced target) for pharmacokinetics study of wine processed Schisandra Chinensis fructus in rats.

Currently the pharmacokinetic (PK) research of herbal medicines is still limited and facing critical technical challenges on quantitative analysis of multi-components from biological matrices which often accompanied by lacking of authentic standards and low concentration. This present work contributes to the development of an integrated strategy for extensive pharmacokinetics assessments, and a selective and sensitive method independent of authentic standards for multi-components analysis based on the use of ultra-performance liquid chromatography/quadrupole-time-of-flight/MSE (UPLC-TOF-MSE) and UPLC-TOF-MRM (rnhanced target). Initially, phytochemicals were identified by UPLC-TOF-MSE analysis, subsequently the identified components were matched with authentic standards and pre-classified, and UPLC-QTOF-MRM method optimized and developed. To guarantee reliable results, three rules are necessary: (1) detection with a mass error of less than 5ppm; (2) same class chemical compositions with structural high similarity between analytes with and without authentic reference substance; (3) a matching retention time between TOF-MRM mode and TOF-MSE within 0.2min. The developed and validated method was applied for the simultaneous determination of 12 lignans in rat plasma after administered with wine processed Schisandra Chinensis fructus (WPSCF) extract. Such an approach was found capable of providing extensive pharmacokinetic profiles of multi-components absorbed into blood after oral administrated with WPSCF extract. The results also indicated that significant difference in pharmacokinetics parameters of dibenzocyclooctadiene lignans was observed between schizandrin and gomisin compounds. For lignans, the absorption via gastrointestinal tract were all rapid and maintained relatively long retention time, especially for schisantherin A and schisantherin B with higher plasma exposure.

Application of temperature-correlated mobility theory for optimizing the MEKC separation of the main lignans from Schisandra Chinensis Fructus and its prescription Yuye Decoction.

The present work shows the application of the temperature-correlated mobility theory for the optimization of the separation and peak alignment of the main lignans from water extracts of traditional Chinese medicine Schisandra Chinensis Fructus as well as its prescription Yuye Decoction (Jade Fluid Decoction; YYD). This is the first application of this theory for MEKC separations, and the data presentation allows a much easier peak tracking and thereby identification of the analytes. Most interestingly, the data obtained and presented in the mobility scale at 298 K, show that Schisantherin A, which is easily mistaken as one of the analytes using traditional time scale, was actually not detected in Schisandra Chinensis Fructus and Yuye Decoction (Jade Fluid Decoction) water extracts. This proves the value of the temperature-correlated mobility scale for method optimization of complex samples. Thus, in the temperature-correlated mobility scale, the optimization of the system conditions for the MEKC separations can easily be achieved by correcting for viscosity changes. Also, the influence of the operating temperature can be monitored in a more distinct way.