PMID: 

Ceska Slov Farm. 2019 ;68(3):95-118. PMID: 31431019

Abstract Title: 

Schisandra chinensis and its phytotherapeutical applications.

Abstract: 

Schisandra (Schisandra chinensis) has been used for centuries as a plant of traditional Chinese medicine. Its biological activity and pharmacological use are associated with dibenzocyclooctadiene lignans, while specific polysaccharides may also be involved. The lignans of schisandra are genus-specific. Their activity has been investigated in hundreds of studies that have confirmed adaptogenic effects, central nervous system stimulation, hepatoprotective effects and potential anticancer potential. This summary review of the literature synthesizes the current state-of-the-art in research on bioactivities of schisandra constituents, description of folk use ofextracts, overview of clinical studies and additional information on in vitro tests bringing insight into mechanisms of action.

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PMID: 

Food Funct. 2020 Mar 18. Epub 2020 Mar 18. PMID: 32186565

Abstract Title: 

Investigation of the active components and mechanisms of Schisandra chinensis in the treatment of asthma based on a network pharmacology approach and experimental validation.

Abstract: 

The aim of this paper was to investigate the active components of Schisandra chinensis in the treatment of asthma and the related mechanisms by a network pharmacology approach. The active components of Schisandra chinensis and the corresponding targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Eight active components in Schisandra chinensis and 56 related targets were screened out according to two indicators, oral bioavailability (OB) and drug-likeness (DL). A total of 132 targets related to asthma were screened out through Therapeutic Target Database (TTD) data. The String database and Cytoscape software were used to build the"drug-active compound-target"network and protein-protein interaction (PPI) network. The key targets were further predicted by the analysis of related biological processes and the pathway-enrichment. A total of 10 intersection targets between Schisandra chinensis and asthma were obtained by building Venn diagrams, and lignans in Schisandra chinensis were found to be associated with asthma. The key targets Ptgs2 and Nos2 were further screened out, and schisandrol B (SCB) was predicted as the most related key component to asthma. A mouse asthma model was established with ovalbumin and aluminum hydroxide for verifying the effect of SCB and related mechanisms. The results showed that SCB could inhibit the gene expression of proinflammatory factors to play a therapeutic role in asthma by reducing the expression of Nos2 and Ptgs2 and regulating the NF-κB signaling pathway to intervene in the process of cell metabolism in mice. These results suggest that SCB can alleviate the severity of asthma through the mechanisms predicted by network pharmacology, and provide a basis for further understanding of the application of Schisandra chinensis in thetreatment of asthma.

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PMID: 

Int Immunopharmacol. 2020 Jan ;78:105983. Epub 2019 Nov 22. PMID: 31767544

Abstract Title: 

Schisandrin A protects against lipopolysaccharide-induced mastitis through activating Nrf2 signaling pathway and inducing autophagy.

Abstract: 

Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Schisandra chinensis (Turcz.) Baill., has anti-oxidant and anti-inflammatory effects, but the effect on masitits has not been studied. Therefore, we investigated the effect of Sch A in cell and mouse models of lipopolysaccharide (LPS)-induced mastitis. Studies in vivo showed that Sch A reduced LPS-induced mammary injury and the production of pro-inflammatory mediators. Sch A also decreased the levels of pro-inflammatory mediators and activated nuclear factor-E2 associated factor 2 (Nrf2) signaling pathway in mouse mammary epithelial cells (mMECs). The Nrf2 inhibitor partially abrogated the downregulation of Sch A on LPS-induced inflammatory response. In addition, LPS stimulation suppressed autophagy, while both Sch A and the autophagy inducer rapamycin activated autophagy in mMECs, which down-regulated inflammatory response. Sch A also restrained LPS-induced phosphorylation of mammalian target of rapamycin (mTOR) and activated AMP-activated protein kinase (AMPK) and unc-51 like kinase 1 (ULK1). In summary, these results suggest that Sch A exerts protective effects in LPS-induced mastitis models by activating Nrf2 signaling pathway and inducing autophagy and the autophagy is initiated by suppressing mTOR signaling pathway and activating AMPK-ULK1 signaling pathway.

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PMID: 

Food Funct. 2019 Dec 11 ;10(12):7755-7766. PMID: 31696200

Abstract Title: 

Anti-fatigue effect of anwulignan via the NRF2 and PGC-1α signaling pathway in mice.

Abstract: 

OBJECTIVE: To examine the anti-fatigue function of anwulignan from Schisandra and its underlying mechanism.METHODS: After an excessive fatigue mouse model was created, anwulignan was administered to the mice, and its effect on exercise tolerance was studied by the weight-bearing swimming test, rotarod test, grip strength test, and tail suspension test. The biochemical indicators closely related to fatigue, including blood urea nitrogen (BUN), lactic acid (LD), lactate dehydrogenase (LDH), and creatine kinase (CK) in the serum; liver glycogen (LG) in the liver tissue; muscle glycogen (MG); inorganic phosphate (Pi) and Annexin V in the gastrocnemius; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA), catalase (CAT), and thiobarbituric acid reactive substances (TBARS); and the 8-hydroxy-2-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) content in both serum and the gastrocnemius were detected. Morphological changes were also observed. The anti-fatigue-related proteins of the NRF2/ARE, Bcl2, and PGC-1α pathways in the gastrocnemius of the mice were detected by western blot.RESULTS: Anwulignan significantly increased the exercise tolerance by decreasing BUN, LD, LDH, CK, Pi, MDA, TBARS, 8-OHdG, ROS, and Annexin V levels and increasing LG, MG, SOD, CAT, and GSH-Px levels, significantly upregulated the expression of NRF2 and Bcl2 proteins, which are anti-oxidation and anti-apoptosis regulators, and also activated the p38MAPK-PGC-1α pathway.CONCLUSION: Anwulignan can increase exercise tolerance and relieve fatigue in an excessive fatigue mouse model. The underlying mechanism may be through its regulatory effect on the NRF2 and PGC-1α signaling pathway. This study will provide scientific data for anwulignan to be developed as a novel and efficient component in anti-oxidant or anti-fatigue health food.

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PMID: 

J Tradit Chin Med. 2019 Dec ;39(6):818-825. PMID: 32186152

Abstract Title: 

Effect of methanol extract of Schisandrae Fructus on high fat diet induced hyperlipidemic mice.

Abstract: 

OBJECTIVE: To investigate the effects and molecular targets of Schisandrae Fructus (SF) methanol extract (SFme) in mice with hyperlipidemia induced by high fat diet.METHODS: We observed changes in body weight, blood serum content of total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglyceride. The extent of accumulation of lipid peroxide due to lipid metabolism disorder also evaluated by measuring malondialdehyde (MDA) level. In addition, after getting gene expression in hepatic tissues, target protein of SFme was identified using a protein interaction database.RESULTS: SFme significantly decreased total cholesterol and triglyceride levels without alteration of body weight in mice, and the liver content of MDA was statistically decreased by SFme. And expression changes of cyclin- dependent kinase 1 (Cdk1) and leucine-rich repeat kinase 2 (Lrrk2) were restored by SFme.CONCLUSION: The effect of SFme on the high- fat-diet induced hyperlipidemia via decreasing total cholesterol and triglyceride levels may involve the expression of Cdk1 and Lrrk2 proteins.

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PMID: 

J Med Food. 2020 Mar 16. Epub 2020 Mar 16. PMID: 32181695

Abstract Title: 

Acidic Polysaccharide Improves the Insulin Resistance in Type 2 Diabetic Rats by Inhibiting Inflammation.

Abstract: 

Polysaccharide fromhas the effect of lowering blood glucose and improving insulin resistance (IR). However, its underlying mechanism remains unclear. In this study, a rat model of type 2 diabetes (T2D) was created to explore whetheracidic polysaccharide (SCAP) would improve the IR in T2D rats by inhibiting inflammation. A combination of a high-fat diet and low dose of streptozotocin (STZ, 30 mg/kg, intraperitoneally) were administered to rats for establishing the T2D model. Then, these T2D rats were orally administered with SCAP (25, 50, or 100 mg/kg) for 8 weeks. The results indicated that SCAP significantly lowered the fasting blood glucose, elevated the fasting insulin, and improved glucose tolerance. SCAP also decreased the serum interleukin-1(IL-1), interleukin-6 (IL-6), tumor necrosis factor-(TNF-), C-reactive protein (CRP), and nuclear factor-B (NF-B) levels, as well as their mRNA expression in the liver tissue. Further, SCAP significantly inhibited the upregulation of phosphorylated c-Jun N-terminal kinase (p-JNK) and NF-B protein, and it increased phosphorylated insulin receptor substrate-1 (p-IRS-1), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), and phosphorylated protein kinase B (p-AKT) protein expression levels significantly. These results suggest that SCAP improves the IR in T2D rats by inhibiting inflammation.

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PMID: 

Nutrients. 2020 Mar 25 ;12(4). Epub 2020 Mar 25. PMID: 32218327

Abstract Title: 

Schisandra Extract and Ascorbic Acid Synergistically Enhance Cognition in Mice Through Modulation of Mitochondrial Respiration.

Abstract: 

Cognitive decline is observed in aging and neurodegenerative diseases, including Alzheimer's disease (AD) and dementia. Intracellular energy produced via mitochondrial respiration is used in the regulation of synaptic plasticity and structure, including dendritic spine length and density, as well as for the release of neurotrophic factors involved in learning and memory. To date, a few synthetic agents for improving mitochondrial function have been developed for overcoming cognitive impairment. However, no natural compounds that modulate synaptic plasticity by directly targeting mitochondria have been developed. Here, we demonstrate that a mixture ofextract (SCE) and ascorbic acid (AA) improved cognitive function and induced synaptic plasticity-regulating proteins by enhancing mitochondrial respiration. Treatment of embryonic mouse hippocampal mHippoE-14 cells with a 4:1 mixture of SCE and AA increased basal oxygen consumption rate. We found that mice injected with the SCE-AA mixture showed enhanced learning and memory and recognition ability. We further observed that injection of the SCE-AA mixture in mice significantly increased expression of postsynaptic density protein 95 (PSD95), an increase that was correlated with enhanced brain-derived neurotrophic factor (BDNF) expression. These results demonstrate that a mixture of SCE and AA improves mitochondrial function and memory, suggesting that this natural compound mixture could be used to alleviate AD and aging-associated memory decline.

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PMID: 

Appl Biochem Biotechnol. 2012 Jul ;167(5):1325-39. Epub 2012 Mar 21. PMID: 22434356

Abstract Title: 

The bioflavonoid galangin suppresses the growth of ehrlich ascites carcinoma in Swiss Albino mice: a molecular insight.

Abstract: 

Bioflavonoids are plant compounds touted for their potential to treat or prevent several diseases including cancer caused by various stress conditions. Galangin (4H-1-Benzopyran-4-one, 3, 5, 7-trihydroxy-2-phenyl-), a flavonoid, is a polyphenolic compound found primarily in medicinal herb, Alpinia galanga. This study aims to demonstrate the galangin as a pharmacological lead compound using in vitro, in vivo, and in silico model targeting specific cancer condition and proteins. The proliferation of MCF-7 and Ehrlich ascites carcinoma (EAC) cells was significantly inhibited with an IC₅₀ of 34.11 and 22.29 μg/ml, respectively. In an animal model system, galangin has inhibited the tumor growth by 73.51% ± 4.742 in EAC-induced Swiss Albino mice with no evidences of mortality as compared to standard drug, 5-fluorouracil. The effectiveness of galangin is proven in an animalsystem suggesting its pharmacokinetics behavior in an animal model which is also complemented by outcome of in silico analysis with more than 88 % of human intestinal absorption and significant Caco-2 cell, MDCK cell, and skin permeability as predicted by in silico methods. Galangin was docked against 19 different proteins involved in tumorogenesis and apoptosis; the energetic analysis indicates that it exhibits higher predicted binding free energy of -12.7 kcal/mol with Bcl-xL protein.

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PMID: 

Pharmacology. 2012 ;89(5-6):247-55. PMID: 22507894

Abstract Title: 

Galangin induces autophagy through upregulation of p53 in HepG2 cells.

Abstract: 

AIM: To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs,induces autophagy of HepG2 cells.METHODS: The MTT[3-(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide]assay was used to measure cell viability. Apoptosis was evaluated by TUNEL assay with flow cytometry, and PARP cleavage was detected by Western blotting. Autophagy was measured by fluorescence microscopy and transmission electron microscopy. Protein expressions were detected by Western blotting. Pifithrin- was used for pretreatment and siRNA was used to knock down p53 expression to explore the pathway mediated by galangin in HepG2 cells. Furthermore, Hep3B cells were used to express the exogenous wild-type p53.RESULTS: Galangin treatment inhibited cell proliferation and induced autophagy (130μ mol/l) and apoptosis (370 μ mol/l). In particular, galangin treatment in HepG2 cells caused (1) an accumulation of autophagosomes, (2) elevated levels of microtubule-associated protein light chain 3, and (3) an increased percentage of cells with vacuoles. p53 expression was also increased. The galangin-induced autophagy was attenuated by the inhibition of p53 in HepG2 cells, and overexpression of p53 in Hep3B cells restored the galangin-induced higher percentage of cells with vacuoles to normal level.CONCLUSION: Our results indicate that galangin not only induced apoptosis but also prompted cell autophagy indifferent concentrations. Galangin mediates autophagy through a p53-dependent pathway in HepG2 cells. Our findings may help in the discovery of a chemotherapeutic drug with the novel pattern of inhibiting cell proliferation for the treatment of hepatocellular carcinoma cells.

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PMID: 

J Asian Nat Prod Res. 2012 ;14(7):626-33. Epub 2012 May 10. PMID: 22575016

Abstract Title: 

Galangin induces apoptosis in hepatocellular carcinoma cells through the caspase 8/t-Bid mitochondrial pathway.

Abstract: 

This study has investigated whether galangin, a flavonol derived from Alpinia officinarum Hance and used as food additives in southern China, induces apoptosis in hepatocellular carcinoma cells (HCCs) by activation of the caspase-8 and Bid pathway. The apoptosis of HCCs was evaluated by in situ uptake of propidium iodide and Hoechst 33258. Protein expressions were detected by Western blotting. Caspase-8 activity was measured using colorimetric method. To confirm the galangin-induced apoptotic pathway, inhibition of caspase-8 activity by Z-IETD-FMK, knockdown of Bid expression with siRNA, and overexpression of Bcl-2 in cells were carried out, respectively. The results show that galangin has significantly induced apoptosis in HCC lines. The caspase-8 is activated, and the cleavage of Bid results in the increase in tBid. The galangin-induced apoptosis is attenuated by Z-IETD-FMK, Bid siRNA, and Bcl-2 overexpression, respectively. However, Bcl-2 fails to suppress caspase-8 activation and the cleavage of Bid. This study has demonstrated that galangin induces apoptosis in HCCs by activating caspase 8/t-Bid mitochondrial pathway. Although Bcl-2 overexpression attenuates galangin-mediated apoptosis of HCCs, it is not mediated by the inhibition of tBid generation and caspase-8 activation.

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