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Journal of Chinese Pharmaceutical Sciences 2016年第4期25卷 233-234页

作者： Ah-Ng Tony Kong siwang yu Department of Pharmaceutics Earnest Mario School of Pharmacy Rutgers The State University of New Jersey School of Pharmaceutical Sciences Peking University Health Science Center

The incidence and mortality of cancer have been increasing alarmingly in China and *** other chronic diseases such as metabolic,cardiovascular,and neuropathies,most cancers,especially metastatic ones,are still essenti... 详细信息

关键词： epigenetics medicines dietary cardiovascular metastatic spite mortality carcinogenesis incidence alterations

Sulforaphane enhances Nrf2-mediated antioxidant responses of skeletal muscle induced by exhaustive exercise in HIIT mice

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Food Science and Human Wellness 2022年第5期11卷 1355-1361页

作者： Yangwenjie Wang Yang Xiang Ruiqi Wang Xiangning Li Jianxiong Wang siwang yu Ying Zhang School of Sport Science Beijing Sport UniversityBeijing 100084China College of Physical Education Yan’an UniversityShaanxi 716000China Faculty of Health Engineeringand SciencesUniversity of Southern QueenslandToowoomba 4350Australia State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologyPeking University School of Pharmaceutical SciencesBeijing 100191China

Nuclear factor erythroid-derived 2-like 2(Nrf2)is the master regulator of antioxidant ***-intensity interval training(HIIT)has been proposed as a time-efficient training program and has become a substantial component of modern training program In the present study,we evaluated the effects of sulforaphane(SFN),a dietary isothiocyanate derived from cruciferous vegetables and a potent Nrf2 activator,on Nrf2-mediated antioxidant defense responses of skeletal muscle induced by exhaustive exercise in HIIT *** C57 BL/6 J mice were randomly allocated into control group,HIIT group,and HIIT pretreated with SFN(HIIT+SFN)*** the third day after completion of a 6-weeks HIIT protocol,an exhaustive treadmill test was conducted in all *** were intraperitoneally injected with SFN(HIIT+SFN group)or PBS(HIIT and control mice)4 times in 3 days prior to the exhaustive treadmill *** results indicated that the 6-weeks HIIT protocol did not increase the antioxidative capacity of skeletal muscle during exhaustive ***,SFN treatment improved anti oxidative capacity of skeletal muscle in response to the acute exhaustive exercise by increasing mRNA and nucleoprotein expression of Nrf2 and these genes involved in antioxidant generation and decreasing blood creatine kinase(CK)and 4-hydroxy-2-nonenal(4-HNE)-modified protein levels in the HIIT mice.

关键词： Sulforaphane Nrf2(nuclear factor erythroid-derived 2-like 2) Skeletal muscle Antioxidant HIIT(high-intensity interval training) Mice

Nrf2-mediated antioxidant and detoxifying enzyme induction by a combination of curcumin and sulforaphane

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Journal of Chinese Pharmaceutical Sciences 2016年第8期25卷 559-569页

作者： Francisco Fuentes yury Gomez Ximena Paredes-Gonzalez Avantika Barve Sujit Nair siwang yu Constance Lay Lay Saw Ah-Ng Tony Kong Facultad de Agronomia e Ingenieria Forestal Pontificia Universidad Cato1ica de Chile Casilla 306-22 Santiago Chile Department of Pharmaceutics Ernest Mario School of Pharmacy Rutgers The State University of New Jersey New Jersey 08854 USA Novartis Institutes for Biomedical Research East Hanover NJ-07470 USA Amrita Cancer Discovery Biology Laboratory Amrita Vishwa Vidyapeetham University Amritapuri Clappana P.O. Kollam Kerala-690525 India School of Pharmaceutical Sciences Peking University Health Science Center Beo'ing 100191 China

The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE （antioxidant response element） response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 （HO-I） and UDP-glucuronosyltransferase-1A （UGT1A）-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR （10 ~tM） and SFN （12.5 ~tM） significantly induced the expression of HO-1 and UGT 1 A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.

关键词： Antioxidant response element, Curcumin, HepG2-C8 cell-s, HO-1, Nrf2, Sulforaphane, UGT 1A1

Cancer chemoprevention by phytochemicals:potential molecular targets,biomarkers and animal models

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Acta Pharmacologica Sinica 2007年第09期28卷 1409-1421页

作者： Ki Han KWON Avantika BARVE siwang yu Mou-Tuan HUANG Ah-Ng Tony KONG Center for Cancer Prevention Research Department of Pharmaceutics Center for Cancer Prevention Research Graduate Program in Pharmaceutical Science Center for Cancer Prevention Research Susan Lehman Cullman Laboratory for Cancer Research Center for Cancer Prevention Research Department of Pharmaceutics Department of Chemical Biology Ernest Mario School of Pharmacy RutgersThe State University of New JerseyPiscatawayNJ 08854USA

Recent studies have strongly indicated that certain daily-consumed dietaryphytochemicals could have cancer protective effects against transgenic mice can-cer models and cancers mediated by carcinogens,irradiations and carcinogenicmetabolites derived from exogenous or endogenous *** cancer-protec-tive effects elicited by these dietary compounds are believed to be due at least inpart to the induction of cellular defense systems including the detoxifying andantioxidant enzymes system,as well as the inhibition of anti-inflammatory andanti-cell growth signaling pathways culminating in cell cycle arrest and/or cell-death,in this review,we summarize the potential mechanisms including the modu-lation of nuclear factor kappaB (NF-kB),cyclooxygenases-2 (COX-2),activatorprotein-1 (AP-1),mitogen-activated protein kinases (MAPKs) and the inductionof phase Ⅱ cellular detoxifying and antioxidant enzymes mediated mainly by theantioxidant response elements (ARE) within the promoter regions of these genesthrough nuclear factor-erythroid 2-related factor 2 (Nff2),a member of the Cap‘n’collar (CNC) family of the basic region-leucine zipper transcription ***,we also review several animal models of carcinogenesis and cancerchemopreventive efficacy studies of these animal models using dietarychemopreventive ***,we discuss the cellular signaling cascadesmediated by Nrf2,NF-kB,AP-1,MAPKs and COX-2,which have been consideredto play pivotal roles in tumor initiation,promotion and progression processes,and could be promising molecular targets for the design of drugs targeting cancerprevention and therapy.

关键词： chemoprevention dietary cancer chemopreventive compounds nuclear factor E2related factor 2 nuclear factor-kappaB activator protein-l mitogen-activated protein kinases

Dose-response relationship between physical activity and nonalcoholic fatty liver disease:A prospective cohort study

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Chinese Medical Journal 2023年第12期136卷 1494-1496页

作者： Pei Li Qingqing Yang Xinping Wang Shengzhi Sun Wangnan Cao siwang yu Siyan Zhan Feng Sun Department of Epidemiology and Biostatics School of Public HealthPeking University Health Science CenterBeijing 100191China Peking University Center for Evidence Based Medical and Clinical Research Beijing 100191China Department of Public Health Shihezi University School of MedicineShiheziXinjiang Uygur autonomous region 832000China School of Public Health Capital Medical UniversityBeijing 100069China Department of Social Medicine and Health E ducation School of Public HealthPeking UniversityBeijing 100191China Department of Molecular and Cellular Pharmacology Peking University School of Pharmaceutical SciencesBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs Beijing 100191China

To the Editor:Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases globally,and this systemic disease carries a substantial economic burden and will result in a greater disease burden in the future.[1]Mass screening of asymptomatic individuals using ultrasonography is not ***,simple,noninvasive tests are required to identify patients with *** fatty liver index(FLI)and hepatic steatosis index(HSI)are accurate and easy to obtain.

关键词： NAFLD liver diseases

The 4^(th) Cancer Chemoprevention Symposium,Beijing 2016——Cancer Chemoprevention by Dietary Phytochemicals and Traditional Chinese Medicines

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Journal of Chinese Pharmaceutical Sciences 2016年第9期25卷 704-706页

作者： Simin Yang siwang yu School of Pharmaceutical Science

2016年7月30～31日，由北京大学药学院主办，深圳福山生物科技有限公司独家赞助的“癌症化学预防论坛-北京2016”顺利召开，来自国内外多家知名研究机构的专家、学者参加了会议，共同探讨化学预防研究的最新进展和发展趋势。

关键词：植物化学物质化学预防癌症中药饮食北京

A novel aza-naphthoquinone inhibits tumor growth by inducing apoptosis

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Journal of Chinese Pharmaceutical Sciences 2018年第9期27卷 600-607页

作者： Li Lei yu Chen Simin Yang Xiangbao Meng siwang yu State Key Laboratory of Natural and Biomimetic Drugs ＂ Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China

Natural product menaquinone has been reported to exhibit antitumor activity mediated by inhibiting IDO-1 enzyme, and naphthoquinone compounds like pyranaphthoquinone have attracted extensive research interests since they share the naphthoquinone pharmacophores. In the present study, a novel series of aza-naphthoquinones was synthesized based on 6,7-dichloroquinoline-5,8-dione structure, and their cytotoxicities were screened using lung cancer cells. Among them CY-26-11 was identified as the most potent one. CY-26-11 concentration-dependently induced apoptosis in A549 human lung adenocarcinoma cells, as indicated by annexin-V staining. Further experimental data show that CY-26-11 down-regulated Bcl-2 while up-regulated Bax and Puma protein levels, and activated caspase-3. Finally, CY-26-11 significantly inhibited the growth of Lewis lung carcinoma xenografts in vivo without significant major toxicities. Taken together, our results demonstrate that CY-26-11 exhibited IDO-l-independent anti-tumor effects both in vitro and in vivo, providing a new anti-tumor mechanism for naphthoquinone compounds.

关键词： Naphthoquinone CY-26-11 Apoptosis Anti-tumor activity

Lanthanides-Induced Cellular Signal Transduction: Implications in Pathogenesis of Fibrosis

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矿物学报 2013年第S1期33卷 34-34页

作者： HE Xia GUO yuting DONG Faqing WANG Kui yu siwang Department of Chemical Biology Peking University School of Pharmaceutical Sciences School of environmental resource and engineering SWUST

With the extensive mining and application of lanthanides in China and worldwide, the potential impact of lanthanides on human health is gaining increasing attentions. The recent etiological association of gadolinium-based contrast agents with nephrogenic systemic fibrosis (NSF) evoked widespread concerns regarding the safety issue of lanthanides. The elucidation of the cellular biological effects of and the signalling cascade induced lanthanides is essential for proper evaluation of their health impacts.

关键词： gadolinium lanthanum nephrogenic systemic fibrosis HEK 293 Cell cycle EGFR PI3K/Akt MAPK TGFβ-1 IntegrinαVβ1

Synthesis and cytotoxicity of kaempferol derivatives

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Journal of Chinese Pharmaceutical Sciences 2017年第9期26卷 660-665页

作者： Yajing Ma Huan Liu Shunan Tang siwang yu Mingying Shang Shaoqing Cai Department of Natural Medicines School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100191 China Department of Chemical Biology School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100191 China

Abstract： In the present study, we developed a simple approach for the structural modifications ofkaempferol （1）. A new compound, 3,5-dihydroxy-2-（4-hydroxyphenyl）-6,8,8-tris（3-methylbut-2-en-1-yl）-4H-chromene-4,7（SH）-dione （5） together with three known compounds, 8-prenylkaempferol （Z）, 6-prenylkaempferol （3） and 6,8-diprenylkaempferol （4）, were synthesized under different reaction conditions. All of derivatives were synthesized in a structural modification way for the first time. Their structures were primarily elucidated by NMR and MS analyses. Compounds 2, 3 and 5 exhibited prominent cytotoxic activity against MDA-231 （IC50 values were 9.45±0.20 μM, 7.15±0.37 μM and 6.92±0.30 μM, respectively） and MCF-7 （ICso values were 10.08±0.57 0M, 10.04±0.23 μM and 2.15±0.20 μM, respectively） breast cancer cells.

关键词： Kaempferol Derivatives Structural modifications Cytotoxicity

Cytotoxicity of Quartz and Montomrillointe in Human Lung Epthlial Cell

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矿物学报 2013年第S1期33卷 37-37页

作者： HUO Tingting DONG Faqin WANG Mingcui SUN Shiyong DENG Jianjun ZHANG Qingbi yu siwang School of Environmental and Resource SWUST Key Laboratory of Solid Waste Treatment and Resource Recycle SWUSTMinistry of Education The Mianyang 404 Hospital Luzhou Medical College Department of Chemical Biology School of Pharmaceutical ScoencePecking University Health Science Center

In this study A549 cell viability, extracellular activities of lactate dehydrogenase (LDH), tumor necrosis factor (TNF)–α and interleukin (IL)-6 levels were investgated after incubation with quartz (KWC-Q4 and KWC-Q3), Nano-SiO2, and KWC-M, the micronucleaus test and comet assay was carried out to evaluate the genotoxicity. The results showed that, there were significant difference in the cell death rate and extracellular LDH activity compared with the control group, and appeared a good linear relationship in certain concentration range. All mineral particle tested can induce the increase of TNF-α after incubation with mineral powders at 200 μg/mL for 3h merely, and significant increase of IL-6 for 24h, the results indicated the inflammatory reaction can be triggered by the exposure of KWC-Q4, KWC-Q3, Nano-SiO2, and KWC-M. The micronucleus test result showed the MNF (Micronucleus frequency) listed as Nano-SiO2>KWC-Q3>KWC-Q4. There is no significant increase of KWC-M compared with the control group, maybe resulted from its high cell death rate at low concentration. The comet assay confirmed the genotoxicity of all samples tested, the DNA damage: KWC-M > Nano-SiO2 > KWC-Q4 > KWC-Q3.

关键词： quartz montmorillonite A549 cytotoxicity genotoxicity