Jinghui Sun

Schisandra polysaccharide inhibits hepatic lipid accumulation by downregulating expression of SREBPs in NAFLD mice

BackgroundHepatoprotective effects of Chinese herbal medicine Schisandra Chinensis (Schisandra) have been widely investigated. However, most studies were focused on its lignan extracts. We investigated the effects of Schisandra polysaccharide (SCP) in a mouse model of non-alcoholic fatty liver disease (NAFLD), and studied its effect on sterol regulatory element binding proteins (SREBPs) and the related genes.MethodsThe mouse model of NAFLD was established by feeding mice with a high-fat diet for 16 weeks. Effect of SCP-treatment (100 mg/kg, once daily for 12 weeks) on biochemical parameters and liver histopathology was assessed. Relative levels of sterol regulatory element-binding proteins (SREBPs) and their gene expressions were determined by quantitative real-time polymerase chain reaction and Western Blot.ResultsSCP significantly reduced the liver index by 12.0%. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol, alanine aminotransferase and aspartate aminotransferase were decreased by 31.3, 28.3, 42.8, 20.1 and 15.5%, respectively. Serum high-density lipoprotein cholesterol was increased by 26.9%. Further, SCP lowered hepatic TC and TG content by 27.0% and 28.3%, respectively, and alleviated fatty degeneration and necrosis of liver cells. A significant downregulation of mRNA and protein expressions of hepatic lipogenesis genes, SREBP-1c, fatty acid synthase and acetyl-CoA carboxylase, and the mRNA expression of liver X receptor α (LXRα) was observed in NAFLD mice treated with SCP. SCP also significantly reduced the hepatic expression of SREBP-2 and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR).ConclusionThese findings demonstrate the hepatoprotective effects of SCP in a mouse model of NAFLD; the effects may be mediated via downregulation of LXRα/SREBP-1c/FAS/ACC and SREBP-2/HMGCR signaling pathways in the liver.

Protective effect of acidic polysaccharide from Schisandra chinensis on acute ethanol-induced liver injury through reducing CYP2E1-dependent oxidative stress

AIM Schisandra chinensis is a well-known traditional Chinese medicine used mainly as a recipe for hepatoprotection. Modern researches have revealed that the hepatoprotection is related to its lignans and crude polysaccharide. In this study, we examined the effect and mechanism of Schisandra chinensis acidic polysaccharide (SCAP) on the liver injury induced by ethanol. MAIN METHODS SCAP was extracted with water extraction and ethanol precipitation. Liver injury models of both mice and HepG2 cells were produced by ethanol. The liver index, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum of the mice and cell culture supernatant were examined; HE staining was performed for observing pathological changes of liver. The malondialdehyde (MDA) level and superoxide dismutase (SOD) activities in serum, liver tissue and HepG2 cells, and triglyceride (TG) content in liver tissue were tested. Western blot was conducted to determine cytochrome P450 2E1 (CYP2E1) expression in liver tissue of mice and HepG2 cells. KEY FINDINGS SCAP significantly reduced serial AST and ALT levels in the injuried liver and HepG2 cells induced by ethanol and also decreased TG level in the liver tissue. SCAP also obviously improved the hepatopathological changes and decreased MDA level as well as increased SOD activities in the serum, liver tissue and HepG2 cells induced by ethanol. Furthermore, Western blot analysis indicated that SCAP significantly inhibited the upregulation of CYP2E1 protein. SIGNIFICANCE SCAP has a protective effect on ethanol-induced liver injury in mice and cells, and the mechanism underlying may be via inhibiting the expression of CYP2E1 protein and then alleviating oxidative stress injury induced by ethanol.

Engineered Hsp Protein Nanocages for siRNA Delivery

The efficient delivery of small interfering RNA (siRNA) to tumor cells still remains a great challenge. Of the various nanocarriers, protein nanocages have attracted extensive interest due to their unique structure and suitable characteristics derived from their proteinaceous nature. However, most reported protein nanocages that are developed are based on virus capsid proteins, which may raise safety concerns, including those related to gene mutation and carcinogenesis. The development of nonviral protein-based systems for siRNA delivery is greatly needed. In this study, a novel siRNA delivery system based on heat shock protein (Hsp) nanocages is developed by a genetic engineering method. The delivery system could condense siRNA into stable complexes and protect the condensed siRNA from degradation. A cellular uptake analysis shows that siRNA is introduced into tumor cells mediated by Hsp-R9 nanocages. Green fluorescent protein (GFP) expression in HeLa-EGFP cells is significantly downregulated by Hsp-R9/siRNA complexes. The results indicate that Hsp nanocages may be a good platform for siRNA delivery into tumor cells.

Pravastatin Decreases Infarct Size Induced by Coronary Artery Ischemia/Reperfusion with Elevated eNOS Expression in Rats

Our previous study showed that pravastatin prevents ischemia and reperfusion-induced lethal ventricular fibrillation in rats. This study explored whether pravastatin decreases myocardial infarct size and this effect is associated with endothelial nitric oxide synthase (eNOS) expression in myocardium. Rats were treated with ischemia (30 minutes) and reperfusion (60 minutes) after chronic oral administration of pravastatin, fluvastatin, or vehicle once daily for 22 days. Electrocardiograms and blood pressure were continuously recorded, myocardial infarct size was measured by TTC-staining, and eNOS expression was measured by western blot. The results showed that pravastatin and fluvastatin significantly reduced myocardial infarct size. No statistical differences were found in the areas at risk among all groups. However, a significant reduction in infarct size was observed in three pravastatin groups and one fluvastatin group compared to control. Both pravastatin and fluvastatin significantly increased eNOS protein expression in ischemic and non-ischemic tissues compared to control. Our results suggest that pravastatin decreases cardiovascular mortality beyond its cholesterol-lowering effect. Pravastatin is more potent than fluvastatin in reducing infarct size. These effects may be associated with elevation of eNOS expression.

Immunomodulatory effect of Schisandra polysaccharides in cyclophosphamide‑induced immunocompromised mice

As a strategy to prevent the well-known immunosuppressant effects of cyclophosphamide (Cyp), the immunomodulatory effects of the polysaccharide extract of the fruit of Schisandra chinensis (Turcz.) Baill. were investigated in the present study. The crude Schisandra polysaccharide (SCP) was obtained by water extraction and alcohol precipitation methods. The total carbohydrate, uronic acid and protein contents were determined using the phenol-sulfuric acid, m-hydroxydiphenyl and Bradford method, respectively. The monosaccharide composition of SCP was determined by high-performance liquid chromatography. ICR mice were randomly divided into control, model, low-dose SCP (0.4 mg/10 g), medium-dose SCP (0.8 mg/10 g) and high-dose SCP (1.6 mg/10 g) groups. The mice in the SCP groups were intragastrically administered SCP once a day for 21 days and those from the control and model groups were administered the same volume of distilled water. Subsequently, the mice in the model and SCP groups were intraperitoneally injected with Cyp (20 mg/kg) once a day for 5 days. The mouse leukocyte count in the peripheral blood as well as thymus and spleen indexes were determined, and the phagocytic function of macrophages was estimated using a carbon clearance test. The thymus and spleen were histomorphologically observed. The levels of tumor necrosis factor-α and interferon-γ were measured by ELISA. Furthermore, antibody formation and spleen lymphocyte proliferation were measured by the serum hemolysin and the MTT method, respectively. The apoptotic rate of splenic lymphocytes was determined by flow cytometric analysis. The results indicated that SCP prevents Cyp-induced impairment of the cellular, humoral and non-specific immunity, and may be an auxiliary immune enhancer for the prevention of immune hypofunction.

Metabolomics study of the therapeutic mechanism of Schisandra chinensis lignans on aging rats induced by D-galactose

Objective The aim of this study was to evaluate the antiaging effect of Schisandra chinensis lignans (SCL) by analyzing the characteristics in the serum of d-galactose (d-gal)-induced rats. Methods Forty male Wistar rats were randomly divided into control group, d-gal model group, low-dose SCL group (50 mg/kg/d), medium-dose SCL group (100 mg/kg/d), and high-dose SCL group (200 mg/kg/d). A serum metabolomics analysis method based on rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry was carried out to study the characteristics of d-gal-induced aging rats and evaluate the antiaging effects of SCL, and multivariate statistical analysis was performed for pattern recognition and characteristic metabolites identification. The relative levels of p19, p53, and p21 genes in the brain tissue were measured by quantitative real-time polymerase chain reaction for investigating the underlying mechanism. Results Metabolomics analysis showed that 15 biomarkers were identified and 13 of them recovered to the normal levels after the administration of SCL. Based on the pathway analysis, the antiaging mechanisms of SCL might be involved in the following metabolic pathways: energy, amino acid, lipid, and phospholipid metabolism. Furthermore, SCL significantly inhibited the mRNA expression level of p19, p53, and p21 in the brain of aging rats induced by d-gal. Conclusion These results suggest that SCL can delay rat aging induced by d-gal through multiple pathways.

Protective effect of Anwulignan against D-galactose-induced hepatic injury through activating p38 MAPK–Nrf2–HO-1 pathway in mice

Background Liver aging is a significant risk factor for chronic liver diseases. Oxidative stress has been considered as a conjoint pathological mechanism for the initiation and progression of liver aging. It has been reported that d-galactose (d-gal)-induced hepatic injury is an experimental model well established closely similar to morphological and functional features of liver aging. Schisandra sphenanthera Rehd. et Wils (S. sphenanthera, Schisandraceae), as a famous tradi-tional Chinese medicine, has been used for thousands of years in China to treat various disorders, including liver dysfunctions. This study was aimed to understand whether Anwulignan, one of the monomeric compounds in the lignans from S. sphenanthera, could improve the hepatic injury induced by d-gal in mice and to examine the possible mechanisms. Methods ICR mice were used to produce hepatic injury by 220 mg kg-1 d-gal subcutaneously once daily for 42 days. The effects of oral Anwulignan on liver index; serial AST and ALT levels; histological changes; SOD, GSH-Px, MDA, and 8-OHdG in the liver and peripheral blood; expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver; and HepG2 cell viability, and decrease caspase-3 contents in liver were examined. Results Anwulignan could significantly increase the liver index, lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the peripheral blood, elevate superoxide dis-mutase (SOD) and glutathione peroxidase (GSH-Px) activities, and decrease malonaldehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG) contents in the peripheral blood and liver. Furthermore, Anwulignan could upregulate the expression of p38 mitogen-activated protein kinase (MAPK), Nrf2, and HO-1 in the liver, increase the HepG2 cell viability, and decrease caspase-3 contents in liver. Conclusion Anwulignan has protective effects against the hepatic injury induced by d-gal, which may be related to its antioxidant capacity through activating p38 MAPK–Nrf2–HO-1 pathway, increases the injured cell viability, and decreases the caspase-3 contents in liver.

Characteristics and Antioxidant Activity of Lignans in Schisandra chinensis and Schisandra sphenanthera from Different Locations

Twenty Schisandra samples were collected from different locations. Contents of 7 lignans in the samples were determined and analyzed by HPLC method coupled with hierarchical clustering analysis (HCA) and principal component analysis (PCA), and the antioxidant capacity of Schisandra from the different locations was evaluated by reducing power, ferric thiocyanate (FTC) and 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) assay. The results showed that there was a significant difference in the content of lignans between Schisandra chinensis and Schisandra sphenanthera. The Schisandra sphenanthera samples in the southwest of China were significantly different from those from the other locations. The antioxidant capacity of Schisandra chinensis was significantly superior to that of Schisandra sphenanthera, and the main antioxidant components were schisandrol A, schisandrol B and schisandrin B based on the result of discrimination analyses. The differences in the chemical composition and antioxidant activity of lignans in Schisandra chinensis and Schisandra sphenanthera from the different locations were investigated in this study, which may provide an experimental basis for the quality control of Schisandra.

Pharmacokinetics and distribution of schisandrol A and its major metabolites in rats

Abstract 1. Schizandrol A is an active component in schisandra, also the representative component for the identification of schisandra. 2. A rapid resolution liquid chromatography coupled with quadruple–time–of–flight mass spectrometry (RRLC–QTOF/MS) was developed to investigate the pharmacokinetics of schizandrol A after its intragastric administration (50 mg/kg) in rats. 3. Schizandrol A was rapidly absorbed (T max = 2.07 h), with a longer duration (t 1/2 = 9.48 h) and larger apparent volume of distribution (Vz/F = 111.81 l/kg) in rats. Schizandrol A can be detected in main organs and the order of its distribution was in the liver > kidney > heart > spleen > brain, particularly higher in the liver. 4. Five schizandrol A metabolites were identified, including 2–demethyl–8(R)–hydroxyl–schizandrin, 3–demethyl–8(R)–hydroxyl–schizandrin, hydroxyl–schizandrin, demethoxy–schizandrin, 2, 3–demethyl–8(R)–hydroxyl–schizandrin, indicating that the hydroxylation and demethylation may be the major metabolic way of schizandrol A. 5. This study defined the pharmacokinetic characteristics of schizandrol A in vivo, and the RRLC–QTOF/MS is more sensitive and less limited by conditions, and needs less samples, which may be a useful resource for the further research and development of schisandrol A.

Compound Schisandra-Ginseng-Notoginseng-Lycium Extract Ameliorates Scopolamine-Induced Learning and Memory Disorders in Mice

Schisandra, Ginseng, Notoginseng, and Lycium barbarum are traditional Chinese medicinal plants sharing cognitive-enhancing properties. To design a functional food to improve memory, we prepared a compound Schisandra-Ginseng-Notoginseng-Lycium (CSGNL) extract and investigated its effect on scopolamine-induced learning and memory loss in mice. To optimize the dose ratios of the four herbal extracts in CSGNL, orthogonal experiments were performed. Mice were administered CSGNL by gavage once a day for 30 days and then mouse learning and memory were evaluated by Morris water maze and step-through tests. The mechanisms of CSGNL improving learning and memory were investigated by assaying acetylcholine (ACh) levels and choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the brain tissues of treated mice. The results showed that CSGNL significantly ameliorated scopolamine-induced learning and memory impairment, at least in part, by modulating ACh levels and ChAT and AChE activities in the mouse brain. Our data support the use of CSGNL as a functional food for learning and memory enhancement.