Research progress on the lignans from the genus Schisandra and their biological activities

The plants of the genus Schisandra belong to the Schisandraceae family.As one of the main active components of genus Schisandra,lignans have rich biological activities,including anti-inflammatory,anti-tumor,anti-HIV and PAF antagonism.This article summarizes and classifies the types and activities of lignans isolated from the genus Schisandra in the past ten years.

Research progress on the triterpenoids from the genus Schisandra and their biological activities

The plants of the genus Schisandra of the Schisandraceae family include the genus Schisandra and the genus Kadsura.In recent years,many kinds of triterpenoids have been isolated from the plants of genus Schisandra.Triterpenoids have attracted the attention of phytochemists and pharmacologists because they have novel skeletons and good anti-HIV,immunosuppressive and anti-tumor activities.This study provides an overview of the triterpenoids from the genus Schisandra and their biological activities.

Schisandra B inhibits proliferation, migration and invasion of bladder cancer by regulating the Wnt/β‑catenin signaling pathway

Objective:To investigate the effects of Schisandra B on proliferation,migration,invasion of bladder cancer and to further investigate its molecular mechanism.Methods:Bladder cancer cells were subjected to different concentrations of Schisandra B solution(0,20,40,80μmol/L).CCK-8 assay was used to detect the effect of schisandra B on bladder cancer cell proliferation.Transwell migration assay and wound healing assay were used to detect the effect of Schisandra B on the migration of bladder cancer cells.Transwell invasion assay was used to detect the effect of schisandra B on invasion ability of bladder cancer cells.The expression levels of intracellularβ-catenin and c-myc protein were measured by western blot.Results:Schisandra B inhibited the proliferation of T24 and UM-UC-3 cells in a concentration and time dependent manner(P<0.05).The rate of wound healing and number of migration and invasion cells decreased with the increase of Schisandra B concentration(P<0.05).The expression ofβ-catenin and c-myc decreased after treatment with Schisandra B in bladder cancer cells(P<0.05).Conclusion:Schisandra B can inhibit the proliferation,migration and invasion of human bladder cancer T24 and UM-UC-3 cells,and the main mechanism for its inhibitory effect may be related to the inactivation of the Wnt/β-catenin signaling pathway.

Study on HPLC method to determine contents of Schisandrin A and Schisandrin B in Schisandra chinensis extraction

The determination method of Schisandrin A and Schisandrin B in Schisandra chinensis was improved with the high performance liquid chromagraphy （HPLC）. The sample was extracted exceedingly in the critical limit of CO2. The retention time of Schisandrin A and Schisandrin B was reduced, with methano/water （75 ： 25） as mobile phase. The wavelength for detection was 254 nm. The R^2 of standard curve was 0.9998 and the relative standard deviation was 2.31% and 3.17% with the recovery of 96.45% and 97.37%, respectively. The result shows that the rate of veracity of this method is higher and it proves that the determination method of Sehisandrin A and Schisandrin B in Schisandra chinensis is a feasible method.

Chemical constituents from Schisandra sphenanthera

The chemical constituents of the stems of Schisandra sphenanthera are described for the first time. This investigation has resulted in the isolation of a new phenolic glycoside （1）, along with seven known compounds. The structure of 1 was assigned by using spectroscopic techniques, including 2D NMR spectra.

Schisanlactone G,a new 3,4-seco-lanostane triterpenoid from Schisandra sphenanthera

A new 3,4-seco-lanostane triterpenoid, schisanlactone G （1）, was isolated from the fruits of Schisandra sphenanthera. Its structure was established on the basis of extensive spectroscopic analysis.

Two New Compounds from Schisandra propinqua var.propinqua

Schisanpropinoic acid(1),a new bergamotane sesquiterpenoid,and schisanpropinin(2),a new tetrahydrofuran lignan with a rare epoxyethane unit,were identified from the stems and leaves of Schisandra propinqua var.propinqua.Their structures were determined based on comprehensive spectroscopic and mass spectrometric analysis.The absolute configuration of 1 was determined by X-ray analysis.Compounds 1 and 2 were tested for their cytotoxic activity against five human tumor cell lines.

Effect of Schisandra chinensis polysaccharide on intracerebral acetylcholinesterase and monoamine neurotransmitters in a D-galactose-induced aging brain mouse model

BACKGROUND： The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase （ACHE） and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE： To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING： Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS： Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical （batch No. 20030804; state drug permit No. H21023095）. A total of 50 six-week-old Kunming mice were randomly divided into five groups： blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS： Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution （0.5 mL/20 g） in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution （0.2 mL/10 g）, respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension （0.2 mL/10 g）, and the mice in the model group were intragastrically infused with the same volume of normal saline （0.2 mL/10 g） once per day for 30 consecutive days. MAIN OUTCOME MEASURES： Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin ＆ eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS： Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine （NA）, dopamine （DA）, and 5-hydroxytryptamine （5-HT） were significantly decreased in the model group （P 〈 0.01 ）. In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups （P 〈 0.01）, while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group （P 〈 0.01）. Drug treatment improved learning and memory abilities （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.

Preparative separation and purification of deoxyschizandrin from Schisandrae Sphenantherae Fructus by high-speed counter-current chromatography

A high-speed counter-current chromatography （HSCCC） method was successfully developed for the preparative separation and purification of deoxyschizandrin from Schisandrae Sphenantherae Fructus in one step. The purity of deoxyschizandrin was 98.5%, and the structure was identified by MS, UV and NMR. This method was simple, fast, convenient and appropriate to prepare pure compound as reference substances for related research on Schisandrae Sphenantherae Fmctus.

Analysis of Essential Oil from Stems of Schisandra Chinensis(Turc z.) Baill

The essential oil of Schisandra Chinensis(Turc z.) Baill was extracted and analyzed. The essential oil was obtained in a 1.8%(mL/100 g material) yield. Forty eight compounds were isolated and characterized from the oil. The results show that the content(20.42%) of β -pinene of naturally essential oil is the highest among the components of the oil,which has laid a foundation for the futher development and application of the stems of Schisandra Chinensis(Turc z.) Baill .

Four new lignans from the leaves and stems of Schisandra propinqua var.sinensis

Four new tetrahydrofuran lignans,schpropinrins A-D(1-4),together with five known ones,were isolated from the leaves and stems of Schisandra propinqua var.sinensis.Their structures,including absolute configurations,were characterized by means of spectroscopic analysis and ECD calculation.Compounds 1-4 featured a ketal or hemiketal substructure at C-7 and all of the isolates were tested for their anti-HIV integrase activity.

Immunomodulatory effect of schisandrae oil in mouse model of autoimmune hepatitis induced by concanavalin A

Objective:To study the immunomodulatory effect of schisandra oil (SCO) in mouse model of autoimmune hepatitis induced by concanavalin A (ConA). Methods: C57BL/6 mice were divided into control group, model group and SCO group. Mice in SCO group were given SCO at 5 mg/kg by intragastric administration every day for 7 days, followed by intravenous injection of ConA at 10 mg/kg. 10 hours after ConA injection, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured by the kits, the expression of inflammatory cytokines like interferon-γ(IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6 (IL-6) in liver was detected by real-time quantitative PCR, and the T cell activation and IFN-γ expression in spleen and MLN were examined by flow cytometry. Results: Compared with control group, each indicator in model group were significantly higher. In SCO preventive treatment group, the levels of serum ALT, AST and LDH were significantly reduced (all P < 0.001), the expression levels of inflammatory cytokines in liver were downregulated, the T cell activation in spleen and MLN was inhibited (P = 0.006 and P = 0.008), the percentages of IFN-γ+ CD8+ and IFN-γ+ CD4+ T cells were decreased, and the frequencies of Th2 and Th17 cells in spleen and MLN were also decreased at the same time. Conclusion: SCO has a protective effect on immune liver injury by inhibiting the activation of T cells and reducing the expression of inflammatory cytokines, which reflects that SCO plays a role in the immunomodulation of autoimmune hepatitis, indicating that SCO is of great significance for the maintenance of autoimmune homeostasis.

Three new nortriterpenoids from Schisandra wilsoniana and their anti-HIV-1 activities

Three new highly oxygenated nortriterpenoids,wilsonianadilactones D-F(1-3),were isolated from the leaves and stems of Schisandra wilsoniana.Their structures were established by means of spectroscopic analysis.Compounds 1-3 showed weak anti-HIV-1 activity with the therapeutic index(TI)values(CC50/EC50)greater than 8.16,14.7,and 17.5,respectively.

Nortriterpenoids from the fruit stalk of Schisandra chinensis (Turcz.) Baill.

Objective:The fruit stalk of Schisandra chinensis(Turcz.)Baill.(S.chinensis)has been found to contain bioactive components similar to the fruit of S.chinensis.Here,we report a recent discovery about new nortriterpenoids with a novel skeleton and anti-gastric cancer activity,which were isolated from the fruit stalk of S.chinensis.Methods:The chemical components of ethyl acetate extract from 70%ethanol extract from S.chinensis fruit stalk were separated,purified,and identified by liquid chromatography methods(silica gel,ODS,HPLC)and extensive spectroscopic analyses(NMR,IR,UV,MS,CD).Results:Two new nortriterpenoids,schilancitrilactone M and 25-hydroxyl schindilactone D(1 and 2),along with ten known nortriterpenoids(3-12)were isolated from the fruit stalk of S.chinensis.The isolated compounds were tested for their cytotoxic activities against MGC-803 cells,and the results showed that compounds 6-8 possessed significant activities with IC50 of 9.01,11.77,and 2.74μmol/L,respectively.Conclusion:Twelve nortriterpenoids including two new compounds were isolated from the fruit stalk of S.chinensis for the first time.Among them,compounds 6-8 showed significant anti-gastric cancer activities.We postulated that the fruit stalk of S.chinensis could be used as an anti-gastric cancer drug.

Schisandrae Fructus oil-induced elevation in serum triglyceride and lipoprotein concentrations associated with physiologic hepatomegaly in mice

Objective:To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus(FSS)and Schisandra chinensis Fructus(FSC)oils in mice.Methods:Mice were orally administered a single dose of SchisandraeFructusoils.Serumandhepatictriglyceride(TG),triglyceridetransferprotein(TTP),apolipoproteinB48(Apo B48),very-low-densitylipoprotein(VLDL),hepatocytegrowth factor(HGF),alanine aminotransfease(ALT)and liver index were measured at 6-120 h post-dosing.Results:FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels,with maximum increases in the liver(by 297%and 340%)at 12 h post-dosing and serum(244%and 439%)at 24-h post-dosing,respectively.Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51%and63%,Apo B48 by 152%and 425%,and VLDL by 67%and 38%in mice,respectively.FSS and FSC oil treatments also increased liver mass by 53%and 55%and HGF by 106%and 174%,but lowered serum ALT activity by 38%and 22%,respectively.Fenofibrate pre/co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41%and 49%at 48 h post-dosing,respectively,but increased hepatic TG contents(by 38%and 33%,respectively)at 12 h post-dosing.Conclusions:Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil(mainly increasing endogenous TG)and FSC oil(mainly elevating exogenous TG).

Schisandra N-butanol extract improves synaptic morphology and plasticity in ovarectomized mice

Preliminary work by our research team revealed that Schisandra, a renowned traditional Chinese medicine, causes learning and memory improvements in ovariectomized mice. This activity was attributed to active ingredients extracted with N-butyl alcohol, named Schisandra N-butanol extract. In this study, ovariectomized mice were pretreated with Schisandra N-butanol extract given by intragastric administration. This treatment led to the enhancement of learning, and an increase in hippocampal CA1 synaptic, surface and postsynaptic density. A decrease in the average size of the synaptic active zone was also observed. These experimental findings showing that Schisandra N-butanol extract improved synaptic morphology indicate an underlying mechanism by which the ability of learning is enhanced in ovariectomized mice.

Schisandra chinensis (Turcz.) Baill

Schisandra chinensis (Turcz.) Baill. is a deciduous woody vine, and belongs to the Schisandraceae family. This species is a horticultural plant with edible fruit. It is used medicinally and for making rope. It is distributed in Hebei, Heilongjiang, Jilin, Liaoning, Nei Mongol, Shanxi

The chemical constituents from Schisandra propinqua var. intermedia

A new cinnamic acid monoterpenoid ester, intermedin C （1）, was isolated from the aerial parts of Schisandra propinqua var. interthedia. The structure of 1 was elucidated by spectroscopic methods including extensive ^1D and 2D NMR techniques.

Pharmacological effects of Schisandra Chinensis Fructus polysaccharide on intestinal protection

Schisandra Chinensis Fructus(SCF)is the fruit of Schisandra chinensis(Turcz.)Baill.,a perennial vine.It was first recorded in Shen Nong′s herbal classic and has a long application history.Studies have shown that SCF has anti-inflammatory,protective liver,antioxidant,antibacterial and other pharmacological effects.Ancient prescriptions are commonly used in the treatment of chronic diarrhea and other intestinal diseases and diabetes.Modern clinical pharmacology features of SCF polysaccharide(SCFP)in diabetes,liver diseases,enteritis and other aspects have achieved excellent results.Gut is an important digestive organ of human body,but intestinal diseases are varied,including Crohn′s disease,ulcerative colitis,intestinal flora imbalance,etc..It is a chronic and non-specific inflammatory disease.The disease is persisted for a long time and the incidence rate is expected to rise.Most of the symptoms are recurrent diarrhea,bloody stool and abdominal pain.It is considered by the World Health Organization as a refractory disease.At present,there is little possibility of complete cure,which is closely related to complex environmental factors,eating habits and heredity.In recent years,clinical studies have found that SCFP has a variety of pharmacological effects on intestinal protection.①Reduce inflammatory factors:intestinal mucositis is a common adverse reaction in patients with chemotherapy.The development of mucositis is related to pro-inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL^(-1)β,Interferon-γ(IFN-γ).SCFP can significantly reduce IL-6 TNF-α,IL^(-1)β,and IL-8,as well as the accumulation of T cells in the process of resisting apoptosis,reduce the inflammatory reaction and protect the damage to villi and crypts,improve the symptoms of small intestinal mucositis caused by weight loss and diarrhea.②Promote immunoglobulin A secretion:intestinal mucosal immunity is the first line of defense of the body′s immune system.Its main antibody is secretory immunoglobulin A,which can destroy and phagocytize microorganisms,bacteria and viruses.SCFP can improve intestinal immunity by increasing the number and activity of T lymphocytes,promoting the secretion of secretory immunoglobulin A,and affecting the activity of a variety of cytokines.③Regulation of intestinal flora:the flora in the intestine has the functions of auxiliary nutrient absorption,biological antagonism and immune regulation,and can form a natural barrier for the host's intestine.When the human intestinal flora is disordered,probiotics will be greatly reduced,harmful bacteria will proliferate and destroy the intestinal environment.Under these conditions,the intake of SCFP significantly increased the number of beneficial bacteria such as bifidobacteria and lactobacillus,and significantly decreased the number of conditional pathogens such as enterococcus and escherichia coli,indicating that SCFP can indeed regulate the intestinal disorder caused by lincomycin hydrochloride to a certain extent. This may be because beneficial bacteria in the intestine metabolize polysaccharides produce short chain fatty acids such as lactic acid and acetic acid, which reduces the pH value in the intestine and inhibits the growth of enterococcus and Escherichia coli. In conclusion, SCFP can treat and protect intestinal diseases to a certain extent, which provides a favorable basis for the treatment of intestinal diseases.

Lignans and sesquiterpenoids from the stems of Schisandra bicolor var. tuberculata

A pair of new tetrahydrofuran lignan enantiomers,(±)-schibiculatin A[(±)-1],a new enedione lignan,schibiculatin B(2),two new cadinane-type sesquiterpenoids,schibiculatins C(3)and D(4),along with two known seco-cadinane-type sesquiterpenoids(5 and 6)and seven known miscellaneous lignans(7-13)were isolated from the stems of Schisandra bicolor var.tuberculata.The structures of 1-4 were elucidated by comprehensive analysis of their spectro-scopic data,quantum chemical calculations,as well as single-crystal X-ray diffraction.A few isolated compounds were tested for their protective activities against corticosterone-induced apoptosis in PC12 cells.Among them,compounds 5 and 6 showed moderate activities.