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.

Schisandrol A, the Major Active Constitute in Schisandra chinensis: A Review of Its Preparation, Biological Activities, and Pharmacokinetics Analysis.

Schisandra chinensis (S. chinensis) has a long history as a traditional Chinese medicine that is astringent, beneficial to vital energy, tonifies the kidney, tranquilizes the heart, etc. Significantly, Schisandrol A (SA) is extracted from S. chinensis and shows surprising and satisfactory biological activity, including anti-inflammatory, hepatoprotective, cardiovascular protection, and antitumor properties, among others. SA has a more pronounced protective effect on central damaged nerves among its numerous pharmacological effects, improving neurodegenerative diseases such as Alzheimer's and Parkinson's through the protection of damaged nerve cells and the enhancement of anti-oxidant capacity. Pharmacokinetic studies have shown that SA has a pharmacokinetic profile with a rapid absorption, wide distribution, maximal concentration in the liver, and primarily renal excretion. However, hepatic and intestinal first-pass metabolism can affect SA's bioavailability. In addition, the content of SA, as an index component of S. chinensis Pharmacopoeia, should not be less than 0.40%, and the content of SA in S. chinensis compound formula was determined with the help of high-performance liquid chromatography (HPLC), which is a stable and reliable method, and it can lay a foundation for the subsequent quality control. Therefore, this paper systematically reviews the preparation, pharmacological effects, pharmacokinetic properties, and content determination of SA with the goal of updating and deepening the understanding of SA, as well as providing a theoretical basis for the study of SA at a later stage.

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.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

A versatile economic strategy by HPLC-CAD for quantification of structurally diverse markers in quality control of Shengmai Formula from raw materials to preparations.

BACKGROUND: Shengmai Formula (SMF), a classic formula in treating Qi-Yin deficiency, is composed of Ginseng Radix et Rhizoma Rubra (GRR), Ophiopogon Radix (OR), and Schisandra chinensis Fructus (SC), and has been developed into various dosage forms including Shengmai Yin Oral Liquid (SMY), Shengmai Capsules (SMC), and Shengmai Injection (SMI). The pharmacological effects of compound Chinese medicine are attributed to the integration of multiple components. Yet the quality criteria of SMF are limited to monitoring schisandrol A or ginsenosides Rg1 and Re, but none for OR. Since the complexity of raw materials and preparations, establishing a economical and unified method for SMF is challenging. It is urgent to simultaneously quantify multiple components with different structures using a universal method for quality control of SMF. Charged aerosol detector (CAD) overcame the above shortcomings owing to its characteristics of high responsiveness, nondiscrimination, and low cost. PURPOSE: We aimed to establish a versatile analysis strategy using HPLC-CAD for simultaneously quantifying the structurally diverse markers in quality control of SMF from raw materials to preparations. METHOD: By optimizing the column, mobile phase, column temperature, flow rate, and CAD parameters, a HPLC-CAD method that integrated multi-component characterization, authenticity identification, transfer information of raw materials and quantitative determination of Shengmai preparations was established. RESULTS: In total 50 components from SMF were characterized (28 in GRR, 13 in SC, and 9 in OR). The differences in raw materials between species of SC and Schisandrae sphenantherae Fructus (SS), processing methods of Ginseng Radix (GR) and GRR, and locations of OR from Sichuan (ORS) and Zhejiang (ORZ) were compared. Fourteen components in 19 batches of SMY, SMC and SMI from different manufacturers were quantified, including 11 ginsenosides and 3 lignans. The multivariate statistical analysis results further suggested that Rb1, Rg1 and Ro were the main differences among Shengmai preparations. CONCLUSION: The established versatile analysis strategy based on HPLC-CAD was proven sensitive, simple, convenient, overcoming the discriminatory effect of UV detector, revealing the composition and transfer information of SMF and applicable for authentication of the ingredient herbs and improving the quality of Shengmai preparations.

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.

Microbial communities of Schisandra sphenanthera Rehd. et Wils. and the correlations between microbial community and the active secondary metabolites.

Background: Schisandra sphenanthera Rehd. et Wils. is a plant used in traditional Chinese medicine (TCM). However, great differences exist in the content of active secondary metabolites in various parts of S. sphenanthera. Do microorganisms critically influence the accumulation of active components in different parts of S. sphenanthera? Methods: In this study, 16S/ITS amplicon sequencing analysis was applied to unravel microbial communities in rhizospheric soil and different parts of wild S. sphenanthera. At the same time, the active secondary metabolites in different parts were detected, and the correlation between the secondary metabolites and microorganisms was analyzed. Results: The major components identified in the essential oils were sesquiterpene and oxygenated sesquiterpenes. The contents of essential oil components in fruit were much higher than that in stem and leaf, and the dominant essential oil components were different in these parts. The dominant components of the three parts were γ-muurolene, δ-cadinol, and trans farnesol (stem); α-cadinol and neoisolongifolene-8-ol (leaf); isosapathulenol, α-santalol, cedrenol, and longiverbenone (fruit). The microbial amplicon sequences were taxonomically grouped into eight (bacteria) and seven (fungi) different phyla. Community diversity and composition analyses showed that different parts of S. sphenanthera had similar and unique microbial communities, and functional prediction analysis showed that the main functions of microorganisms were related to metabolism. Moreover, the accumulation of secondary metabolites in S. sphenanthera was closely related to the microbial community composition, especially bacteria. In endophytic bacteria, Staphylococcus and Hypomicrobium had negative effects on five secondary metabolites, among which γ-muurolene and trans farnesol were the dominant components in the stem. That is, the dominant components in stems were greatly affected by microorganisms. Our results provided a new opportunity to further understand the effects of microorganisms on the active secondary metabolites and provided a basis for further research on the sustainable utilization of S. sphenanthera.

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.

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.

Untargeted metabolomics reveals intervention effects of wine-processed Schisandra chinensis polysaccharide on Alzheimer's disease mice.

Schisandra chinensis (Turcz.) Baill (SC) is a traditional sedative in China, with wide applications for treating various neurological disorders. Its polysaccharide component has been gaining increased attention for its potential in nerve protection. While raw SC is the primary focus of current research, its processed products are primarily utilized as clinical medicines. Notably, limited research exists on the mechanisms underlying the effects of wine-processed Schisandra chinensis polysaccharide (WSCP) in Alzheimer's Disease (AD). Therefore, this study seeks to assess the therapeutic impact of WSCP on AD mice and investigate the underlying mechanisms through biochemical and metabolomics analyses. The results demonstrate that WSCP exerts significant therapeutic effects on AD mice by enhancing learning and memory abilities, mitigating hippocampal neuronal damage, reducing abnormal amyloid-beta (Aß) deposition, and attenuating hyperphosphorylation of Tau. Biochemical analysis revealed that WSCP can increase SOD content and decrease MDA, IL-6, and TNF-α content in AD mice. Furthermore, serum metabolomic results showed that WSCP intervention can reverse metabolic disorders in AD mice. 43 endogenous metabolites were identified as potential biomarkers for WSCP treatment of AD, and the major metabolic pathways were Ala, Glu and Asp metabolism, TCA cycle. Overall, these findings will provide a basis for further development of WSCP.

Synthetic consortia of four strains promote Schisandra chinensis growth by regulating soil microbial community and improving soil fertility.

MAIN CONCLUSION: Synthetic consortia performed better in promoting Schisandra chinensis growth than individual strains, and this result provides valuable information for the development of synthetic microbial fertilizers. Schisandra chinensis is an herbal medicine that can treat numerous diseases. However, the excessive reliance on chemical fertilizers during the plantation of S. chinensis has severely restricted the development of the S. chinensis planting industry. Plant growth-promoting rhizobacteria (PGPR) can promote the growth of a wide range of crops, and synthetic consortia of them are frequently superior to those of a single strain. In this study, we compared the effects of four PGPR and their synthetic consortia on S. chinensis growth. The pot experiment showed that compared with the control, synthetic consortia significantly increased the plant height, biomass, and total chlorophyll contents of S. chinensis, and their combined effects were better than those of individual strains. In addition, they improved the rhizosphere soil fertility (e.g., TC and TN contents) and enzyme activities (e.g., soil urease activity) and affected the composition and structure of soil microbial community significantly, including promoting the enrichment of beneficial microorganisms (e.g., Actinobacteria and Verrucomicrobiota) and increasing the relative abundance of Proteobacteria, a dominant bacterial phylum. They also enhanced the synergistic effect between the soil microorganisms. The correlation analysis between soil physicochemical properties and microbiome revealed that soil microorganisms participated in regulating soil fertility and promoting S. chinensis growth. This study may provide a theoretical basis for the development of synthetic microbial fertilizers for S. chinensis.

Dibenzocyclooctadiene Lignans from Schisandra chinensis with Anti-Inflammatory Effects.

Schisandra chinensis (Schisandraceae) is a medicinal plant widely used in traditional Chinese medicine. Under the name Wu Wei Zi, it is used to treat many diseases, especially as a stimulant, adaptogen, and hepatoprotective. Dibenzocyclooctadiene lignans are the main compounds responsible for the effect of S. chinensis. As a part of ongoing studies to identify and evaluate anti-inflammatory natural compounds, we isolated a series of dibenzocyclooctadiene lignans and evaluated their biological activity. Furthermore, we isolated new sesquiterpene 7,7-dimethyl-11-methylidenespiro[5.5]undec-2-ene-3-carboxylic acid. Selected dibenzocyclooctadiene lignans were tested to assess their anti-inflammatory potential in LPS-stimulated monocytes by monitoring their anti-NF-κB activity, antioxidant activity in CAA assay, and their effect on gap junction intercellular communication in WB-ras cells. Some S. chinensis lignans showed antioxidant activity in CAA mode and affected the gap junction intercellular communication. The anti-inflammatory activity was proven for (-)-gomisin N, (+)-γ-schisandrin, rubrisandrin A, and (-)-gomisin J.

Inhibitory effect of benzocaine from Schisandra chinensis on Alternaria alternata.

The clinical effects of Schisandra chinensis against human disease are well-documented; however, studies on its application in controlling plant pathogens are limited. Here, we investigated its inhibitory effect on the growth of Alternaria alternata, a fungus which causes significant post-harvest losses on apples, known as black spot disease. S. chinensis fruit extract exhibited strong inhibitory effects on the growth of A. alternata with an EC50 of 1882.00 mg/L. There were 157 compounds identified in the extract by high performance liquid chromatography-mass spectrometry, where benzocaine constituted 14.19% of the extract. Antifungal experiments showed that the inhibitory activity of benzocaine on A. alternata was 43.77-fold higher than the crude extract. The application of benzocaine before and after A. alternata inoculation on apples prevented the pathogen infection and led to mycelial distortion according to scanning electron microscopy. Transcriptome analysis revealed that there were 4226 genes differentially expressed between treated and untreated A. alternata-infected apples with benzocaine. Metabolomics analysis led to the identification of 155 metabolites. Correlation analysis between the transcriptome and metabolome revealed that benzocaine may inhibit A. alternata growth via the beta-alanine metabolic pathway. Overall, S. chinensis extract and benzocaine are environmentally friendly plant-based fungicides with potential to control A. alternata.

Effect of pinoresinol-lariciresinol reductases on biosynthesis of lignans with substrate selectivity in Schisandra chinensis.

Schisandra lignans are the main bioactive compounds found in Schisandra chinensis fruits, such as schisandrol lignans and schisandrin lignans, which play important roles in organ protection or other clinical roles. Pinoresinol-lariciresinol reductase (PLR) plays a pivotal role in plant lignan biosynthesis, however, limited research has been conducted on S. chinensis PLR to date. This study identified five genes as ScPLR, successfully cloned their coding sequences, and elucidated their catalytic capabilities. ScPLR3-5 could recognize both pinoresinol and lariciresinol as substrates, and convert them into lariciresinol and secoisolariciresinol, respectively, while ScPLR2 exclusively catalyzed the conversion of (+)-pinoresinol into (+)-lariciresinol. Transcript-metabolite correlation analysis indicated that ScPLR2 exhibited unique properties that differed from the other members. Molecular docking and site-directed mutagenesis revealed that Phe271 and Leu40 in the substrate binding motif were crucial for the catalytic activity of ScPLR2. This study serves as a foundation for understanding the essential enzymes involved in schisandra lignan biosynthesis.

Establishment of cluster of differentiation 20 immobilized cell membrane chromatography for the screening of active antitumor components in traditional Chinese medicine.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant tumors occurring in B or T lymphocytes, and no small molecule-positive drugs to treat NHL have been marketed. Cluster of differentiation 20 (CD20) is an important molecule regulating signaling for the life and differentiation of B lymphocytes and possesses the characteristics of a drug target for treating NHL. 2-Methoxyestradiol induces apoptosis in lymphoma Raji cells and CD20 protein is highly expressed by Raji lymphoma cells. Therefore, in this study, a CD20-SNAP-tag/CMC model was developed to validate the interaction of 2-methoxyestradiol with CD20. 2-Methoxyestradiol was used as a small molecule control compound, and the system was validated for good applicability. The cell membrane chromatography model was combined with high-performance liquid chromatography ion trap time-of-flight mass spectroscopy (HPLC-IT-TOF-MS) in a two-dimensional system to successfully identify, analyze, and characterize the potential active compounds of Schisandra chinensis (Turcz.) Baill. extract and Lysionotus pauciflorus Maxim. extract, including Schisandrin A, Schizandrol A, Schizandrol B, Schisantherin B, and Nevadensin, which can act on CD20 receptors. The five potential active compounds were analyzed by non-linear chromatography. The thermodynamic and kinetic parameters of their interaction with CD20 were also analyzed, and the mode of interaction was simulated by molecular docking. Their inhibitory effects on lymphoma cell growth were assessed using a Cell Counting Kit-8 (CCK-8). Nevadensin and Schizandrin A were able to induce apoptosis in Raji cells within a certain concentration range. In conclusion, the present experiments provide some bases for improving NHL treatment and developing small molecule lead compounds targeting CD20 with low toxicity and high specificity.

Lignan contents of Schisandra chinensis (Turcz.) Baill. from different origins-A new model for evaluating the content of prominent components of Chinese herbs.

BACKGROUND: As a traditional Chinese herbal medicine, Schisandra chinensis exhibits various effects such as liver protection, blood sugar regulation, blood lipid regulation, immune function regulation, antidepressant activity, etc. However, because of its intricate composition, diverse origins, and medicinal effects depending on complex compound groups, there are differences in the lignan composition of S. chinensis from different origins. Therefore, it is currently difficult to evaluate the quality of medicinal materials from plants of different origins using a single qualitative quality control index. PURPOSE: This paper aims to investigate the potential relationship between the lignan components of S. chinensis from different origins and to establish stable assessment indices for determining the lignan content of S. chinensis from multiple perspectives. METHODS: In this study, we collected S. chinensis samples of seven major origins in China, and randomly sampled 6-9 batches of each origin for a total of 60 batches. The lignan content was determined by HPLC, and its distribution law of the ratio of each lignan component of S. chinensis to Schisandrol A content was analyzed. Combining network pharmacology and differential analysis between samples, the stable and effective substances used as quality markers were determined. RESULTS: There were some correlations among the lignan contents of S. chinensis, some correlations between schisandrin A and other lignans of S. chinensis could be determined. The ratio of each component to the indicator component schisandrol A was evenly distributed and reflected the lignan content of S. chinensis to some extent. Four substances (schisandrol A, schisandrol B, schisantherin A, and schisandrin C) were determined by network pharmacology combined with the analysis results of HCA, PCA and PLS-DA to further optimize the model. They displayed a strong connection with the core target, a large contribution rate to the principal components, and a stable content in each batch of samples, suggesting that these components may be the main active substances of S. chinensis lignans. Therefore, they could be used as main indicators evaluating the advantages and disadvantages of S. chinensis by examining the consistency of component proportions. CONCLUSION: This method can intuitively evaluate the content of main lignans in S. chinensis. This quality assessment model is an exploration of the multi-component comprehensive evaluation system of S. chinensis, providing a new concept for the quality evaluation system of Chinese herbal medicines.

Zhumian Granules improves PCPA-induced insomnia by regulating the expression level of neurotransmitters and reducing neuronal apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep problems, according to Traditional Chinese medicine (TCM) philosophy, are attributed to the imbalance between yin and yang. Zhumian Granules, also known as Sleep-aid Granules or ZG, are a traditional Chinese herbal remedy specifically designed to alleviate insomnia. This formula consists of many components, including Wu Wei Zi (Schisandrae Chinensis Fructus), Suan Zao Ren (Ziziphi Spinosae Semen), and other medicinal plants. According to the pharmacology of Traditional Chinese Medicine (TCM), Wu Wei Zi and Suan Zao Ren have the ability to relax the mind and promote sleep. When taken together, they may balance the opposing forces of yin and yang. Therefore, ZG may potentially be used as a therapeutic treatment for insomnia. AIM OF THE STUDY: This research was specifically developed to establish a strong empirical basis for the subsequent advancement and utilization of ZG in the management of insomnia. This research aimed to gather empirical data to support the effectiveness of ZG, thereby providing useful insights into its potential therapeutic advantages for persons with insomnia. MATERIALS AND METHODS: This study utilized Zhumian Granules (ZG), a traditional Chinese herbal decoction, to examine its sedative and hypnotic effects on mice with PCPA-induced insomnia. The effects were assessed using the pentobarbital-induced sleep test (PIST), Morris water maze test (MWM), and autonomic activity test. The levels of neurotransmitters in each group of mice were evaluated using UPLC-QQQ-MS. The impact of ZG on the quantity and structure of hippocampal neurons was seen in brain tissue slices using immunofluorescence labeling. RESULTS: ZG was shown to possess active sedative properties, effectively lowering the distance of movement and lengthening the duration of sleep. ZG mitigated the sleeplessness effects of PCPA by elevating the levels of 5-hydroxytryptamine (5-HT), 4-aminobutyric acid (GABA), and 5-hydroxyindoleacetic acid (5-HIAA), while reducing the levels of dopamine (DA) and norepinephrine (NE), as well as decreasing neuronal death. CONCLUSIONS: This research confirmed the sedative and hypnotic properties of ZG and elucidated its probable mechanism involving neurotransmitters.

Schisandrin B from Schisandra chinensis alleviated pain via glycine receptors, Nav1.7 channels and Cav2.2 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.

The extraction, purification, structural features, bioactivities, and applications of Schisandra chinensis polysaccharides: A review.

Schisandra chinensis, as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo, including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields.

Extraction, purification, structural characterization, and bioactivities of the genus Schisandra polysaccharides: A review.

The genus Schisandra, a member of the Magnoliaceae family, is a well-known tonic traditional Chinese medicine with a long history of traditional medicinal and functional food used in China. Polysaccharides are one of its main active constituents, which have a wide range of bioactivities, such as anti-inflammatory, anti-tumor, neuroprotection, anti-diabetes, hepatoprotection, immunomodulation, and anti-fatigue. In this paper, we review the extraction, isolation, purification, structural characterization, bioactivities, as well as structure-activity relationship of polysaccharides from the genus Schisandra. In conclusion, we hope that this review could provide reference for the subsequent research on structural, bioactivities, development and application of the genus Schisandra polysaccharides.