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Sam Sik Kang - One of the best experts on this subject based on the ideXlab platform.
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Growth Inhibition and Cell Cycle Arrest in the G0/G1 by Schizandrin, a Dibenzocyclooctadiene Lignan Isolated from Schisandra chinensis, on T47D Human Breast Cancer Cells
2016Co-Authors: Sam Sik Kang, Sang Kook LeeAbstract:Schizandrin is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Biological activities including hepatoprotective, antiviral and neuroprotective effects of schizandrin and other dibenzocyclooctadiene lignans have been reported previously. However, the antiprolif-erative effect of schizandrin against human cancer cells has been poorly determined to date. This study exam-ined the antiproliferative effect of schizandrin in human breast cancer cells. Schizandrin exhibited growth inhibitory activities in cultured human breast cancer cells, and the effect was the more profound in estrogen receptor (ER)-positive T47D cells than in ER-negative MDA-MB-231 cells. When treated with the compound in T47D cells, schizandrin induced the accumulation of a cell population in the G0/G1 phase, which was further demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A, CDK2 and CDK4. These results suggest that schizandrin inhibits cell proliferation through the induction of cell cycle arrest with modulating cell cycle-related proteins in human breast cancer cells. Copyright © 2009 John Wiley & Sons, Ltd
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growth inhibition and cell cycle arrest in the g0 g1 by schizandrin a dibenzocyclooctadiene lignan isolated from schisandra chinensis on t47d human breast cancer cells
Phytotherapy Research, 2009Co-Authors: Sam Sik KangAbstract:Schizandrin is one of the main dibenzocyclooctadiene lignans present in the fruit of Schisandra chinensis (Schisandraceae). Biological activities including hepatoprotective, antiviral and neuroprotective effects of schizandrin and other dibenzocyclooctadiene lignans have been reported previously. However, the antiproliferative effect of schizandrin against human cancer cells has been poorly determined to date. This study examined the antiproliferative effect of schizandrin in human breast cancer cells. Schizandrin exhibited growth inhibitory activities in cultured human breast cancer cells, and the effect was the more profound in estrogen receptor (ER)-positive T47D cells than in ER-negative MDA-MB-231 cells. When treated with the compound in T47D cells, schizandrin induced the accumulation of a cell population in the G0/G1 phase, which was further demonstrated by the induction of CDK inhibitors p21 and p27 and the inhibition of the expression of cell cycle checkpoint proteins including cyclin D1, cyclin A, CDK2 and CDK4. These results suggest that schizandrin inhibits cell proliferation through the induction of cell cycle arrest with modulating cell cycle-related proteins in human breast cancer cells. Copyright © 2009 John Wiley & Sons, Ltd.
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Effects of Schisandrin on Transcriptional Factors in Lipopolysaccharide-
2009Co-Authors: Pretreated Macrophages, Lian Yu Guo, Tran Manh Hung, Kihwan Bae, Sehyun Jang, Eun Myoung Shin, Ji Won Chung, Sam Sik Kang, Hyun Pyo Kim, Yeong Shik KimAbstract:Schisandrin is the main active ingredient isolated from Schisandra chinensis Baill. Recent studies have demonstrated that Schisandrin exhibits anti-inflammatory effects in vivo and in vitro. In this study, we examined whether the order of lipopolysaccharide (LPS) treatment affects the mechanism of Schisandrin anti-inflammatory activity. We found that the anti-inflammatory mechanisms are not the same depending on whether macrophages were treated with Schisandrin before or after LPS. The main difference is that inhibitor kappaBα (IκBα) degradation was not inhibited when macrophages were pretreated by LPS before Schisandrin and was weakly inhibited when macrophages were pretreated by Schisandrin before LPS
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Effects of Schisandrin on Transcriptional Factors in Lipopolysaccharide-
2009Co-Authors: Hung Tran Manh, Pretreated Macrophages, Lian Yu Guo, Tran Manh Hung, Kihwan Bae, Sehyun Jang, Eun Myoung Shin, Ji Won Chung, See Profile, Sam Sik KangAbstract:Effects of Schisandrin on transcriptional factors in lipopolysaccharide-pretreated macrophage
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anti inflammatory effects of Schisandrin isolated from the fruit of schisandra chinensis baill
European Journal of Pharmacology, 2008Co-Authors: Tran Manh Hung, Eun Myoung Shin, Hong Yu Zhou, Yoo Na Hong, Sam Sik KangAbstract:Abstract Schisandrin is the main active ingredient isolated from the fruit of Schisandra chinensis Baill. Recent studies have demonstrated that Schisandrin exhibits anti-oxidative effects in vivo. In the present study, the effect of Schisandrin on plasma nitrite concentration in lipopolysaccharide (LPS)-treated mice was evaluated. It also significantly inhibited carrageenan-induced paw edema and acetic acid-induced vascular permeability in mice. Furthermore, Schisandrin had a protective effect on lipopolysaccharide (LPS)-induced sepsis. In vitro, our results are the first that show that the anti-inflammatory properties of Schisandrin result from the inhibition of nitric oxide (NO) production, prostaglandin E2 (PGE2) release, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, which in turn results from the inhibition of nuclear factor-kappaB (NF-κB), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activities in a RAW 264.7 macrophage cell line.
Hanski Leena - One of the best experts on this subject based on the ideXlab platform.
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The influence of dibenzocyclooctadiene lignans on macrophage glutathione and lipid metabolism associated with Chlamydia pneumoniae-induced foam cell formation
'Elsevier BV', 2021Co-Authors: Kortesoja Maarit, Taavitsainen Eveliina, Hanski LeenaAbstract:Triggered by changes in macrophage redox status and lipid metabolism, foam cells represent a hallmark of atherosclerosis. Induction of macrophage foam cell formation by Chlamydia pneumoniae, a gram-negative human pathogen, has been established in various earlier studies in vitro and in vivo. Oxidation of low-density lipoprotein (LDL) by C. pneumoniae and alterations in macrophage lipid metabolism do not require chlamydial replication, making conventional antibiotics useless in the intervention of the process. In this work, we report on the ability of Schisandrin B and Schisandrin C, two dibenzocyclooctadiene lignans, to suppress the C. pneumoniae -induced foam cell formation in RAW264.7 macrophages. This effect was accompanied with the upregulation of PPARγ, a nuclear receptor acting as a major transcriptional regulator of lipid metabolism and inflammatory responses. Schisandrin B and Schisandrin C also increased the total intracellular glutathione content of the macrophages. In the case of Schisandrin B, this was accompanied with the upregulation of GSH biosynthetic genes glutamate cysteine ligase (both the catalytic and the modifier subunits GCLc and GCLm) as well as gamma-glutamyl transpeptidase GGT1. In addition, Schisandrin B and Schisandrin C upregulated the expression of a lipid transport protein ABCA1 gene mediating cholesterol efflux from macrophages translating into a reduction in total cholesterol concentration in the Schisandrin B -treated cells. Collectively, these data indicate that both Schisandrin B and Schisandrin C are able to alleviate the pathogenic consequences of C. pneumoniae infection in macrophages by altering the cellular redox balance and lipid trafficking.Peer reviewe
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Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers
Multidisciplinary Digital Publishing Institute, 2020Co-Authors: Taavitsaine Eveliina, Kortesoja Maari, Uu Tanja, Johansson, Niklas G., Hanski LeenaAbstract:Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan Schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of Schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan Schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia–host interactions. These data indicate that Schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation
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Assaying Chlamydia pneumoniae Persistence in Monocyte-Derived Macrophages Identifies Dibenzocyclooctadiene Lignans as Phenotypic Switchers
'MDPI AG', 2020Co-Authors: Taavitsaine Eveliina, Kortesoja Maari, Uu Tanja, Johansson, Niklas G., Hanski LeenaAbstract:Antibiotic-tolerant persister bacteria involve frequent treatment failures, relapsing infections and the need for extended antibiotic treatment. The virulence of an intracellular human pathogen C. pneumoniae is tightly linked to its propensity for persistence and means for its chemosensitization are urgently needed. In the current work, persistence of C. pneumoniae clinical isolate CV6 was studied in THP-1 macrophages using quantitative PCR and quantitative culture. A dibenzocyclooctadiene lignan Schisandrin reverted C. pneumoniae persistence and promoted productive infection. The concomitant administration of Schisandrin and azithromycin resulted in significantly improved bacterial eradication compared to sole azithromycin treatment. In addition, the closely related lignan Schisandrin C was superior to azithromycin in eradicating the C. pneumoniae infection from the macrophages. The observed chemosensitization of C. pneumoniae was associated with the suppression of cellular glutathione pools by the lignans, implying to a previously unknown aspect of chlamydia-host interactions. These data indicate that Schisandrin lignans induce a phenotypic switch in C. pneumoniae, promoting the productive and antibiotic-susceptible phenotype instead of persistence. By this means, these medicinal plant -derived compounds show potential as adjuvant therapies for intracellular bacteria resuscitation.Peer reviewe
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Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells.
'Elsevier BV', 2019Co-Authors: Kortesoja Maarit, Karhu Elina, Olafsdottir, Elin Soffia, Freysdottir Jona, Hanski LeenaAbstract:To access publisher's full text version of this article click on the hyperlink belowRedox signaling has been established as an essential component of inflammatory responses, and redox active compounds are of interest as potential immunomodulatory agents. Dibenzocyclooctadiene lignans isolated from Schisandra chinensis, a medicinal plant with widespread use in oriental medicine, have been implicated to possess immunomodulatory properties but their effects on the human innate immune system cells have not been described. In this contribution, data are presented on the impact of Schisandrin, Schisandrin B and Schisandrin C on human monocytic cell redox status, as well as their impact on dendritic cell maturation and T cell activation capacity and cytokine production. In THP-1 cells, levels of intracellular reactive oxygen species (ROS) were elevated after 1 h exposure to Schisandrin. Schisandrin B and Schisandrin C decreased cellular glutathione pools, which is a phenotype previously reported to promote anti-inflammatory functions. Treatment of human primary monocytes with the lignans during their maturation to dendritic cells did not have any effect on the appearance of surface markers HLA-DR and CD86 but Schisandrin B and Schisandrin C suppressed the secretion of cytokines interleukin (IL)-6, IL-10 and IL-12 by the mature dendritic cells. Dendritic cells maturated in presence of Schisandrin C were further cocultured with naïve CD4+ T cells, resulting in reduced IL-12 production. In THP-1 cells, Schisandrin B and Schisandrin C reduced the IL-6 and IL-12 production triggered by E. coli lipopolysaccharide and IL-12 production induced by an infection with Chlamydia pneumoniae. In conclusion, the studied lignans act as immunomodulatory agents by altering the cytokine secretion, but do not interfere with dendritic cell maturation. And the observed effects may be associated with the ability of the lignans to alter cellular redox status.CIMO (The Centre for International Mobility
Yongjia Shen - One of the best experts on this subject based on the ideXlab platform.
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preparative separation and purification of deoxySchisandrin and γ Schisandrin from schisandra chinensis turcz baill by high speed counter current chromatography
Journal of Chromatography A, 2005Co-Authors: Tianhui Huang, Pingniang Shen, Yongjia ShenAbstract:Abstract High-speed counter-current chromatography (HSCCC) was successfully applied to the preparative separation and purification of deoxySchisandrin and γ-Schisandrin from the crude petroleum ether extracts of Schisandra chinensis (Turcz.) Baill . The optimum solvent system composed of n -hexane–methanol–water (35:30:3, v/v) led to the successful preparation of deoxySchisandrin and γ-Schisandrin. The analysis of HPLC for each peak fraction of preparative HSCCC showed that the purity of deoxySchisandrin (8 mg) was over 98% and γ-Schisandrin (12 mg) was over 96% from 100 mg of the crude petroleum ether extracts in one-step separation.
Xin Zhou - One of the best experts on this subject based on the ideXlab platform.
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application of preparative high speed counter current chromatography for isolation and separation of schizandrin and gomisin a from schisandra chinensis
Journal of Chromatography A, 2005Co-Authors: Jinyong Peng, Guorong Fan, Xin ZhouAbstract:Following an initial cleaning-up step on the D101 macroporous resin, a preparative high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane–ethyl acetate–methanol–water (1:0.9:0.9:1, v/v) was used to isolate and separate schizandrin and gomisin A from Schisandra chinensis. A total of 107 mg schizandrin and 36 mg gomisin A with purities of 99.5% and 99.1% were obtained from 400 mg crude extract in one-step elution and less than 3 h, and the structure identification was performed by UV, IR, MS, 1 H NMR and 13 C NMR.
Dewei Zhao - One of the best experts on this subject based on the ideXlab platform.
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inhibition of udp glucuronosyltransferases ugts activity by constituents of schisandra chinensis
Phytotherapy Research, 2015Co-Authors: Jinhui Song, Zhong-ze Fang, Peipei Dong, Frank J Gonzalez, Libin An, Wentao Li, Yanyan Zhang, Xue Wu, Lixuan Wang, Dewei ZhaoAbstract:Structure–activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, Schisandrin, Schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among Schisandrin A, Schisandrin, and Schisandrin C toward UGT1A1 and UGT1A3: Schisandrin A > Schisandrin > Schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb–drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis. Copyright © 2015 John Wiley & Sons, Ltd.
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inhibition of udp glucuronosyltransferases ugts activity by constituents of schisandra chinensis
Phytotherapy Research, 2015Co-Authors: Jinhui Song, Zhong-ze Fang, Peipei Dong, Frank J Gonzalez, Yanyan Zhang, Lixuan Wang, Li Cui, Xiaoyu Sun, Dewei ZhaoAbstract:Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, Schisandrin, Schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among Schisandrin A, Schisandrin, and Schisandrin C toward UGT1A1 and UGT1A3: Schisandrin A > Schisandrin > Schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.
