Multi-omics analysis reveals mechanism of Schisandra chinensis lignans and acteoside on EMT in hepatoma cells via ERK1/2 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC), a globally common cancer, often presents late and shows high resistance to chemotherapy, resulting in suboptimal treatment efficacy. Components from traditional Chinese medicines have been recognized for their anti-cancer properties. OBJECTIVE: Exploring the mechanism of Schisandra chinensis lignans and acteoside in suppressing Epithelial-Mesenchymal Transition (EMT) in hepatoma cells through the Extracellular signal-Regulated Kinases (ERK)1/2 pathway and identifying biomarkers, molecular subtypes, and targets via multi-omics for precision oncology. METHODS: Proliferation was assessed using cell counting kit-8 (CCK-8) assays, with scratch and transwell assays for evaluating invasion and migration. Flow cytometry quantified apoptosis rates. Expression levels of CCL20, p-ERK1/2, c-Myc, Vimentin, and E-cadherin/N-cadherin were analyzed by real-time PCR and Western blot. Tumor volume was calculated with a specific formula, and growth. RESULTS: The Schisandra chinensis lignans and acteoside combination decreased CCL20 expression, inhibited hepatoma proliferation and migration, and enhanced apoptosis in a dose- and time-dependent manner. Molecular analysis revealed increased E-cadherin and decreased N-cadherin, p-ERK1/2, c-Myc, and Vimentin expression, indicating ERK1/2 pathway modulation. In vivo, treated nude mice showed significantly reduced tumor growth and volume. CONCLUSION: Schisandra chinensis lignans and acteoside potentially counteract CCL20-induced EMT, invasion, and migration in hepatocellular carcinoma cells via the ERK1/2 pathway, enhancing apoptosis. Multi-omics analysis further aids in pinpointing novel biomarkers for precision cancer therapy.

Improvement of nucleotide content of Cordyceps tenuipes by Schisandra chinensis: fermentation process optimization and application prospects.

Nucleotides are important components and the main indicators for judging Cordyceps quality. In this paper, the mixed fermentation process of Schisandra chinensis and Cordyceps tenuipes was systematically studied, and it was proposed that the fermentation products aqueous extract (S-ZAE) had antioxidant activity and anti-AChE ability. Herein, the results of a single factor showed that S. chinensis, yeast extract, inoculum amount, and pH had significant effects on nucleotide synthesis. The fermentation process optimization results were 3% glucose, 0.25% KH2PO4, 2.1% yeast extract, and S. chinensis 0.49% (m/v), the optimal fermentation conditions were 25℃, inoculum 5.8% (v/v), pH 3.8, 6 d. The yield of total nucleotides in the scale-up culture was 0.64 ± 0.027 mg/mL, which was 10.6 times higher than before optimization. S-ZAE has good antioxidant and anti-AChE activities (IC50 0.50 ± 0.050 mg/mL). This fermentation method has the advantage of industrialization, and its fermentation products have the potential to become good functional foods or natural therapeutic agents.

Integrated spatial metabolomics and network pharmacology to explore the pharmacodynamic substances and mechanism of Radix ginseng-Schisandra chinensis Herb Couple on Alzheimer's disease.

Radix ginseng and Schisandra chinensis have been extensively documented in traditional Chinese medicine (TCM) for their potential efficacy in treating dementia. However, the precise mechanism of their therapeutic effects remains to be fully elucidated. In this study, air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and network pharmacology are used to investigate the pharmacodynamics and mechanism underlying the herbal combination consisting of Radix ginseng-Schisandra chinensis (RS) in a rodent model for Alzheimer's disease (AD). Brain histopathological findings suggested that RS attenuates hippocampal damage in AD mice, making this combination a potential AD treatment. Twenty-eight biomarkers were identified by spatial metabolomics analysis, which are intricately linked to neuroinflammation, neurotransmitter imbalance, energy deficiency, oxidative stress, and aberrant fatty acid metabolism in AD. The total extract of RS (TE) affected 22 of these biomarkers, with the small molecule components of RS (SN) significantly influencing 19 and the large molecule components of RS (PR) impacting 14. Nine small molecule components are likely to dominate the pharmacodynamics of RS. We constructed a target interaction network based on the corresponding bioactivities that revealed relationships amongst 11 key biomarkers, 8 active ingredients and 12 critical targets. This research illustrates the immense potential of spatial metabolomics and network pharmacology in the study of TCM, revealing the targets and mechanisms underlying herbal formulas.

Phenolic compound profiling and antioxidant potential of different types of Schisandra henryi in vitro cultures.

Schisandra henryi is an endemic species of medicinal potential known from traditional Chinese medicine. As part of this study, a complex biotechnological and phytochemical assessment was conducted on S. henryi with a focus on phenolic compounds and antioxidant profiling. The following in vitro cultures were tested: microshoot agar and callus, microshoot agitated, and suspension, along with the microshoot culture in PlantForm bioreactors. Qualitative profiling was performed by ultra-high-performance liquid chromatography with a photodiode array detector coupled with ion-trap mass spectrophotometry with electrospray ionization and then quantitative analysis by high-performance liquid chromatography with a diode array detector using standards. In the extracts, mainly the compounds from procyanidins were identified as well as phenolic acids (neochlorogenic acid, caffeic acid, protocatechuic acid) and catechin. The highest content of phenolic compounds was found for in vitro agar microshoot culture (max. total content 229.87 mg/100 g DW) and agitated culture (max. total content 22.82 mg/100 g DW). The max. TPC measured using the Folin-Ciocalteu assay was equal to 1240.51 mg GAE/100 g DW (agar microshoot culture). The extracts were evaluated for their antioxidant potential by the DPPH, FRAP, and chelate iron ion assays. The highest potential was indicated for agar microshoot culture (90% of inhibition and 59.31 nM/L TEAC, respectively). The research conducted on the polyphenol profiling and antioxidant potential of S. henryi in vitro culture extracts indicates the high therapeutic potential of this species. KEY POINTS: • Different types of S. henryi in vitro cultures were compared for the first time. • The S. henryi in vitro culture strong antioxidant potential was determined for the first time. • The polyphenol profiling of different types of S. henryi in vitro cultures was shown.

Effect of vinegar steaming on the composition and structure of Schisandra chinensis polysaccharide and its anti-colitis activity.

In this study, infrared spectroscopy, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) technology were applied to systematically explain the Schisandra chinensis's polysaccharide transformation in configuration, molecular weight, monosaccharide composition, and anti-ulcerative colitis (UC) activity after vinegar processing. Scanning electron microscopic results showed that the appearance of S. chinensis polysaccharide changed significantly after steaming with vinegar. The MALDI-TOF-MS results showed that the mass spectra of raw S. chinensis polysaccharides (RSCP) were slightly lower than those of vinegar-processed S. chinensis polysaccharides (VSCP). The RSCP showed higher peaks at m/z 1350.790, 2016.796, and 2665.985, all with left-skewed distribution, and the molecular weights were concentrated in the range of 1300-3100, with no higher peak above m/z 5000. The VSCPs showed a whole band below m/z 3000, with m/z 1021.096 being the highest peak, and the intensity decreased with the increase of m/z. In addition, compared to RSCPs, VSCPs can significantly increase the content of intestinal short-chain fatty acids (SCFAs). This study showed that the apparent morphology and molecular weight of S. chinensis's polysaccharides significantly changed after steaming with vinegar. These changes directly affect its anti-UC effect significantly, and its mechanism is closely related to improving the structure and diversity of gut microbiota and SCFA metabolism.

Simultaneous separation and determination of seven biphenyl cyclooctene lignans in Schisandra chinensis and its preparations by micellar electrokinetic chromatography with dual organic solvent system.

INTRODUCTION: Gomisin is a natural dibenzo cyclooctene lignan, which is mainly derived from the family Magnoliaceae. It has anti-inflammatory, antioxidant, anti-tumor, anti-aging, and hypoglycemic effects. Gomisins play important roles as medicines, nutraceuticals, food additives, and cosmetics. OBJECTIVE: The objective of this study is to establish a micellar electrokinetic chromatography (MEKC) method for simultaneous separation and determination of seven biphenyl cyclooctene lignans (Gomisin D, E, G, H, J, N, and O) in Schisandra chinensis and its preparations. METHODS: The method was optimized by studying the effects of the main parameters on the separation. The method has been validated and successfully applied to the determination of seven Gomisins in S. chinensis and its preparations. RESULTS: In the separation system, the running buffer was composed of 20 mM Na2HPO4, 8.0 mM sodium dodecyl sulfate (SDS), 11% (v/v) methanol, and 6.0% (v/v) ethanol. A diode array detector was used with a detection wavelength of 230 nm, a separation voltage of 17 kV, and an operating temperature of 25°C. Under this condition, the seven analytes were separated at baseline within 20 min, and a good linear relationship was obtained with correlation coefficient ranging from 0.9919 to 0.9992. The limit of detection (LOD, S/N = 3) and the limit of quantification (LOQ, S/N = 10) ranged from 0.8 to 0.9 µg/mL and from 2.6 to 3.0 µg/mL, respectively. The recovery rate was between 99.1% and 102.5%. CONCLUSION: The experimental results indicated that this method is suitable for the separation and determination of seven Schisandra biphenyl cyclooctene lignan compounds in real samples. At the same time, it provides an effective reference for the quality control of S. chinensis and its preparations.

Effect and mechanism of gomisin D on the isoproterenol induced myocardial injury in H9C2 cells and mice.

We established myocardial injury models in vivo and in vitro to investigate the cardioprotective effect of gomisin D obtained from Schisandra chinensis. Gomisin D significantly inhibited isoproterenol-induced apoptosis and hypertrophy in H9C2 cells. Gomisin D decreased serum BNP, ANP, CK-MB, cTn-T levels and histopathological alterations, and inhibited myocardial hypertrophy in mice. In mechanisms research, gomisin D reversed ISO-induced accumulation of intracellular ROS and Ca2+. Gomisin D further improved mitochondrial energy metabolism disorders by regulating the TCA cycle. These results demonstrated that gomisin D had a significant effect on isoproterenol-induced myocardial injury by inhibiting oxidative stress, calcium overload and improving mitochondrial energy metabolism.

Based on HPLC and HS-GC-IMS Techniques, the Changes in the Internal Chemical Components of Schisandra chinensis (Turcz.) Baill. Fruit at Different Harvesting Periods Were Analyzed.

Schisandra chinensis, as a traditional Chinese herbal medicine, has clear pharmacological effects such as treating asthma, protecting nerves and blood vessels, and having anti-inflammatory properties. Although the Schisandra chinensis fruit contain multiple active components, the lignans have been widely studied as the primary pharmacologically active compound. The volatile chemical components of Schisandra chinensis include a large amount of terpenes, which have been proven to have broad pharmacological activities. However, when to harvest to ensure the highest accumulation of pharmacologically active components in Schisandra chinensis fruits is a critical issue. The Schisandra chinensis fruit trees in the resource nursery were all planted in 2019 and began bearing fruit in 2021. Their nutritional status and tree vigor remain consistently good. The content of lignans and organic acids in the fruits of Schisandra chinensis over seven different harvest periods was tested, and the results of high-performance liquid chromatography (HPLC) indicated that the lignan content was higher, at 35 mg/g, in late July, and the organic acid content was higher, at 72.34 mg/g, in early September. If lignans and organic acids are to be selected as raw materials for pharmacological development, the harvest can be carried out at this stage. Using HS-GC-IMS technology, a total of 67 volatile flavor substances were detected, and the fingerprint of the volatile flavor substances in the different picking periods was established. It was shown by the results that the content of volatile flavor substances was the highest in early August, and 16 flavor substances were selected by odor activity value (OAV). The variable importance in projection (VIP) values of 16 substances were further screened, and terpinolene was identified as the key volatile flavor substance that caused the aroma characteristics of Schisandra chinensis fruit at different harvesting periods. If the aroma component content of Schisandra chinensis fruit is planned to be used as raw material for development and utilization, then early August, when the aroma component content is higher, should be chosen as the time for harvest. This study provides a theoretical basis for the suitable harvesting time of Schisandra chinensis for different uses, and promotes the high-quality development of the Schisandra chinensis industry.

Optimization of the Extraction Process and Biological Activities of Triterpenoids of Schisandra sphenanthera from Different Medicinal Parts and Growth Stages.

Schisandra sphenanthera Rehd. et Wils., as a traditional Chinese medicine, has important medicinal value. In the market, the availability of the fruit of S. sphenanthera mainly relies on wild picking, but many canes and leaves are discarded during wild collection, resulting in a waste of resources. The canes and leaves of S. sphenanthera contain various bioactive ingredients and can be used as spice, tea, and medicine and so present great utilization opportunities. Therefore, it is helpful to explore the effective components and biological activities of the canes and leaves to utilize S. sphenanthera fully. In this study, the response surface method with ultrasound was used to extract the total triterpenoids from the canes and leaves of S. sphenanthera at different stages. The content of total triterpenoids in the leaves at different stages was higher than that in the canes. The total triterpenoids in the canes and leaves had strong antioxidant and antibacterial abilities. At the same time, the antibacterial activity of the total triterpenoids against Bacillus subtilis and Pseudomonas aeruginosa was stronger than that against Staphylococcus aureus and Escherichia coli. This study provides the foundation for the development and utilization of the canes and leaves that would relieve the shortage of fruit resources of S. sphenanthera.

The protective effect of Schisandra chinensis (Turcz.) Baill. polysaccharide on DSS-induced ulcerative colitis in mice via the modulation of gut microbiota and inhibition of NF-κB activation.

BACKGROUND: Schisandra chinensis (Turcz.) Baill, a fruit utilized in traditional Chinese medicine (TCM), has a long history of medical application. It has been used to treat diseases of the gastrointestinal tract. Schisandra chinensis (Turcz.) Baill polysaccharide (SACP) is an important biologically active ingredient that has been shown to have a variety of beneficial effects including immune regulation and anti-oxidative properties. Ulcerative colitis (UC) is a complicated gastrointestinal inflammatory disease. We explore the protective effect of SACP against UC. RESULTS: Schisandra chinensis (Turcz.) Baill polysaccharide significantly reduced the disease activity index (DAI) and levels of myeloperoxidase(MPO) and malondialdehyde (MDA) in colonic tissue. It also alleviated weight loss and histopathological damage of mice. The expression of MUC2 and occludin proteins was increased and the barrier function of the colonic mucosa was enhanced by SACP treatment. NF-κB pathway activation was also inhibited and the production of pro-inflammatory cytokines was decreased whereas anti-inflammatory cytokines were increased. 16SrDNA sequencing of fecal flora showed that SACP increased the abundance of Muribaculaceaeunclassified, LachnospiraceaeNK4A136group and reduced the abundance of Bacteroides and Erysipelatoclostridium. CONCLUSION: Schisandra chinensis (Turcz.) Baill polysaccharide can protect against Dextran Sulfate Sodium Salt (DSS)-induced ulcerative colitis in mice. © 2023 Society of Chemical Industry.

[Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise].

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

Rapid identification of chemical compositions of three species of Schisandra chinensis by ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry.

Schisandra chinensis is a traditional Chinese medicine, which has played an important role in the field of medicine and food. In this study, ultra-high-performance liquid chromatography quadrupole-orbitrap-mass spectrometry was used to rapidly classify and identify the chemical compositions. Note that 32, 28, and 30 kinds of compounds were successfully identified from northern Schisandra chinensis, vinegar-processed Schisandra chinensis, and wine-processed Schisandra chinensis, respectively. The cleavage patterns of various components including lignans, organic acids, flavonoids, and terpenoids were summarized, and the effects of different processing methods on Schisandra chinensis were analyzed through chemical composition. This method realized the rapid classification and identification of raw Schisandra chinensis and two different processed products, and provided references for improving the traditional processing methods, strengthening quality control, and ensuring safe clinical application.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.

Schisandra henryi-A Rare Species with High Medicinal Potential.

Schisandra henryi (Schisandraceae) is a plant species endemic to Yunnan Province in China and is little known in Europe and America. To date, few studies, mainly performed by Chinese researchers, have been conducted on S. henryi. The chemical composition of this plant is dominated by lignans (dibenzocyclooctadiene, aryltetralin, dibenzylbutane), polyphenols (phenolic acids, flavonoids), triterpenoids, and nortriterpenoids. The research on the chemical profile of S. henryi showed a similar chemical composition to S. chinensis-a globally known pharmacopoeial species with valuable medicinal properties whichis the best-known species of the genus Schisandra. The whole genus is characterized by the presence of the aforementioned specific dibenzocyclooctadiene lignans, known as "Schisandra lignans". This paper was intended to provide a comprehensive review of the scientific literature published on the research conducted on S. henryi, with particular emphasis on the chemical composition and biological properties. Recently, a phytochemical, biological, and biotechnological study conducted by our team highlighted the great potential of S. henryi in in vitro cultures. The biotechnological research revealed the possibilities of the use of biomass from S. henryi as an alternative to raw material that cannot be easily obtained from natural sites. Moreover, the characterization of dibenzocyclooctadiene lignans specific to the Schisandraceae family was provided. Except for several scientific studies which have confirmed the most valuable pharmacological properties of these lignans, hepatoprotective and hepatoregenerative, this article also reviews studies that have confirmed the anti-inflammatory, neuroprotective, anticancer, antiviral, antioxidant, cardioprotective, and anti-osteoporotic effects and their application for treating intestinal dysfunction.

Analysis of Volatile Components in Dried Fruits and Branch Exudates of Schisandra chinensis with Different Fruit Colors Using GC-IMS Technology.

To investigate the volatile components of Schisandra chinensis (Turcz.) Bail (commonly known as northern Schisandra) of different colors and to explore their similarities and differences, to identify the main flavor substances in the volatile components of the branch exudates of northern schisandra, and finally to establish a fingerprint map of the volatile components of the dried fruits and branch exudates of northern Schisandra of different colors, we used GC-IMS technology to analyze the volatile components of the dried fruits and branch exudates of three different colors of northern Schisandra and established a fingerprint spectra. The results showed that a total of 60 different volatile chemical components were identified in the branch exudates and dried fruits of Schisandra. The components of germplasm resources with different fruit colors were significantly different. The ion mobility spectrum and OPLS-DA results showed that white and yellow fruits were more similar compared to red fruits. The volatile components in dried fruits were significantly higher than those in branch exudates. After VIP (variable importance in projection) screening, 41 key volatile substances in dried fruits and 30 key volatile substances in branch exudates were obtained. After screening by odor activity value (OAV), there were 24 volatile components greater than 1 in both dried fruits and branch exudates. The most important contributing volatile substance was 3-methyl-butanal, and the most important contributing volatile substance in white fruit was (E)-2-hexenal.

Separation and Identification of an Antimicrobial Substance from Schisandra chinensis Extract against Streptococcus mutans KCCM 40105 Strain.

This study aimed to isolate and identify antibacterial compounds from Schisandra chinensis (S. chinensis) that are effective against the Streptococcus mutans KCCM 40105 strain. First, S. chinensis was extracted using varying concentrations of ethanol, and the resulting antibacterial activity was evaluated. The 30% ethanol extract of S. chinensis showed high activity. The fractionation and antibacterial activity of a 30% ethanol extract from S. chinensis were examined using five different solvents. Upon investigation of the antibacterial activity of the solvent fraction, the water and butanol fractions showed high activity, and no significant difference was found. Therefore, the butanol fraction was chosen for material exploration using silica gel column chromatography. A total of 24 fractions were obtained from the butanol portion using silica gel chromatography. The fraction with the highest antibacterial activity was Fr 7. From Fr 7, thirty-three sub-fractions were isolated, and sub-fraction 17 showed the highest level of antibacterial activity. A total of five peaks were obtained through the pure separation of sub-fraction 17 using HPLC. Peak 2 was identified as a substance exhibiting a high level of antibacterial activity. Based on the results of UV spectrometry, 13C-NMR, 1H-NMR, LC-MS, and HPLC analyses, the compound corresponding to peak number 2 was identified as tartaric acid.

[Optimization of ethanol reflux extraction process of Ziziphi Spinosae Semen- Schisandrae Sphenantherae Fructus based on network pharmacology combined with response surface methodology].

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.

[Identification of Q-markers for Schisandrae Sphenantherae Fructus in treating drug-induced liver injury based on network pharmacology, fingerprint and quantitative analysis].

This study aims to establish the ultra-performance liquid chromatography(UPLC) fingerprint and multi-indicator quantitative analysis method for Schisandrae Sphenantherae Fructus(SSF) and to screen out the potential quality markers(Q-markers) of hepatoprotection based on network pharmacology. The similarity analysis was performed using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System, which showed that the similarity of the fingerprints of 15 samples from different regions ranged from 0.981 to 0.998. Eighteen common components were identified, from which 3 differential components were selected by cluster analysis and principal component analysis. The "component-target-pathway" network was built to predict the core components related to the hepatoprotective effects. Fourteen core components were screened by network pharmacology. They acted on the targets such as AKT1, CCND1, CYP1A1, CYP3A4, MAPK1, MAPK3, NOS2, NQO1, and PTGS2 to regulate the signaling pathways of lipid metabolism and atherosclerosis, hepatitis B, interleukin-17, and tumor necrosis factor. Considering the chemical measurability, characteristics, and validity, schisantherin A, anwulignan, and schisandrin A were identified as the Q-markers. The content of schisantherin A, anwulignan, and schisandrin A in the test samples were 0.20%-0.57%, 0.13%-0.33%, and 0.42%-0.70%, respectively. Combining the fingerprint, network pharmacology, and content determination, this study predicted that schisantherin A, anwulignan, and schisandrin A were the Q-markers for the hepatoprotective effect of SSF. The results can provide reference for improving the quality evaluation standard and exploring the hepatoprotective mechanism of SSF.

Raw and Wine Processed Schisandra chinensis Regulate NREM-Sleep and Alleviate Cardiovascular Dysfunction Associated with Insomnia by Modulating HPA Axis.

Clinical studies have shown that insomnia and anxiety are usually accompanied by cardiovascular dysfunction. In traditional Chinese medicine, Schisandra chinensis (SC) and wine processed Schisandra chinensis (WSC) are mainly used for the treatment of dysphoria, palpitation and insomnia. However, little attention was paid to its mechanism. In this study, we monitored the effect of SC and WSC on the nervous system and cardiovascular system of free-moving rats in the real-time. Our results show that SC and WSC can alleviate cardiovascular dysfunction while promoting sleep, and we further explored their potential mechanisms. HPLC-QTOF-MS was used for the quality control of chemical components in SC and WSC. Data sciences international (DSI) physiological telemetry system was applied to collect the electroencephalogram (EEG), electrocardiogram (ECG) and other parameters of free-moving rats to understand the effects of long-term intake of SC and WSC on rats. The content of Cortisol (CORT), neurotransmitters and amino acids in rat pituitary and hypothalamus were analyzed by UPLC-MS to determine the activity of HPA axis. The expression of melatonin receptor MT1 was analyzed by immunofluorescence technique. Our results suggested that SC and WSC may play the role of promoting sleep by increasing the expression level of melatonin receptor MT1 in hypothalamus, and modulate the activity of HPA axis by regulating the levels of the related neurotransmitters and amino acid, so as to improve the abnormal cardiovascular system of rats. This study may provide theoretical support for explicating the advantages of SC and other phytomedicines in the treatment of insomnia.

Preparation of 5-hydroxymethylfurfural from Schisandra chinensis (Turcz.) Baill by high-speed counter-current chromatography: Comparison of conventional and consecutive separation.

Schisandra chinensis is a plant with high medicinal value, which contains many medicinal ingredients, including 5-hydroxymethylfurfural. In the present study, an efficient method based on high-speed counter-current chromatography was established for the preparation of 5-hydroxymethylfurfural from Schisandra chinensis. Petroleum ether-ethyl acetate-methanol-water (2:5:2:5, v/v) was selected as the solvent system for high-speed counter-current chromatography. In order to improve the yield of single separation, the sample size was continuously optimized and improved. The results showed that 1,250 mg was the most suitable sample size, and 41 mg of the target compound with 97% purity was obtained in a single run. To further improve the yield, consecutive high-speed counter-current chromatography was introduced and compared with the results of a high-speed counter-current chromatography single run. The results showed that although the purity was reduced to 92%, 430 mg of the target compound was obtained from 12.5 g of ethanol extract within 670 min after 10 consecutive injections. This indicated that consecutive separation not only increased the yield of the target compound, but also saved the separation time and greatly improved the separation efficiency of high-speed counter-current chromatography.