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Novel cytotoxic steroidal glyco.ides from the roots of Liriope muscari

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Chinese Journal of Natural Medicines 2015年第6期13卷 461-466页

作者： LI Yong-Wei QI Jin ZHANG Yuan-Yuan HUANG Zhen KOU Jun-Ping ZHOU Shui-Ping ZHANG Yu YU Bo-Yang State Key Laboratory of Natural Medicines Department of Complex Prescription of TCM China Pharmaceutical University tasly Research and Development Institute Tasly Pharmaceutical Co. Ltd.

The present study was designed to investigate the chemical co.stituents and bioactivities of the roots of Liriope muscari(Decne.) L.H. Bailey. The co.pounds were isolated through various chromatography techniques, including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were elucidated by infrared(IR), mass spectrometric(MS), 1D- and 2D-NMR analyses in co.parison with reference data. In addition, the cytotoxicity of these co.pounds against human breast cancer MDA-MB-435 cells was evaluated by the MTT assay. Two new steroidal glyco.ides, 25(R, S)-rusco.enin-1-O-[β-D-fuco.yranosyl(1→2)]-[ β-D-xylopyranosyl(1→3)]-β-D-gluco.yranoside(Liriopem I, 1) and 25(R, S)- rusco.enin-1-O-[β-D-fuco.yranosyl(1→2)]-[β-D-xylopyranosyl(1→4)]-β-D-fuco.yranoside(Liriopem II, 2) and two known co.pounds LM-S6(3) and DT-13(4) were isolated and identified. Liriopem I(1), liriopem II(2) and DT-13(4) showed remarkable cytotoxicity with IC50 values being(0.58 ± 0.08),(0.05 ± 0.10), and(0.15 ± 0.09) μg·m L-1, respectively. In summary, co.pounds 1 and 2 identified in the present study exerted cytotoxicity against breast cancer cells, providing a basis for future development of these co.pounds as novel anticancer agents.

关键词： Liriope muscari Steroidal glyco.ides Cytotoxicity

Xiao Ke Qing improves glyco.etabolism and ameliorates insulin resistance by regulating the PI3K/Akt pathway in KKAy mice

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Frontiers of Medicine 2018年第6期12卷 688-696页

作者： Xiaoqing Li Xinxin Li Genbei Wang Yan Xu Yuanyuan Wang Ruijia Hao Xiaohui Ma Department of Pharmaco.ogy and Toxico.ogy Tasly Pharmaceutical Co.Ltd.Tianjin 300410China

Xiao Ke Qing (XKQ) granule has been clinically used to treat type 2 diabetes mellitus (T2DM) for 10 years in Chinese traditional medication. However, its mechanisms against hyperglycemia remain poorly understood. This study aims to investigate XKQ mechanisms on diabetes and diabetic liver disease by using the KKAy mice model. Our results indicate that XKQ can significantly reduce food and water intake. XKQ treatment also remarkably decreases both the fasting blood gluco.e and blood gluco.e in the oral gluco.e tolerance test. Additionally, XKQ can significantly decrease the serum alanine aminotransferase level and liver index and can alleviate the fat degeneration in liver tissues. Moreover, XKQ can ameliorate insulin resistance and upregulate the expression of IRS-1, PI3K (p85), p-Akt, and GLUT4 in the skeletal muscle of KKAy mice. XKQ is an effective drug for T2DM by ameliorating insulin resistance and regulating the PI3K/Akt signaling pathway in the skeletal muscle.

关键词： XKQ type 2 diabetes mellitus KKAy mice PI3K/Akt pathway diabetic liver disease

Suitable soil moisture co.tents for water use efficiency and saponins accumulation in Panax notoginseng

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Chinese Herbal Medicines 2021年第2期13卷 267-273页

作者： Yu-jie Zheng Peng-guo Xia Hong-guang Zhao Jian-fen Zheng Wei-guo Chai Zong-suo Liang Kai-jing Yan Laboratory of Plant Seco.dary Metabolism and Regulation of Zhejiang Province College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou 310018China Institute of Biotechnology Hangzhou Academy of Agricultural SciencesHangzhou 310024China yunnan tasly notoginseng pharmaceutical co. LtdWenshan 663000China

Objective:The moisture co.tent in the soil directly affects the yield and quality of Panax notoginseng,especially at the age of three years ***,the suitable moisture for the growth of *** is *** this study,the effects of different soil moisture on the growth of *** were ***:Four different water treatments(0.45 field capacity(FC),0.60 FC, 0.70 FC, and 0.85 FC) were set up in Shilin co.nty,yunnan Province,*** water co.sumption and daily dynamic of water co.sumption were determined daily(from April 21 to October 18,2012),and the daily dynamic of water co.sumption under different weather co.ditions(sunny and rainy) was *** transpiration co.fficient and water use efficiency were calculated through dry matter accumulation and total water *** of saponins of roots of *** were analyzed by HPLC after treated,and the soil moisture co.tent suitable for the growth of *** was estimated by regression fitting of the active ingredient accumulation and the soil moisture ***:The water co.sumption of 0.85 FC,0.70 FC,0.60 FC and 0.45 FC were 2.89,3.68,3.37 and 2.73 kg/plant per day,*** water co.sumption of *** from June to August was greater than other *** daily dynamic of water co.sumption on sunny days and sunny days after rain showed a "double peak" feature,and it showed a "single peak" feature on rainy *** water uses efficiency(WUE) of 0.85 FC,0.70 FC,0.60 FC and 0.45 FC were 2.51,3.32,4.59,3.39 gDW/kg H_(2)O,*** increase of soil moistu re co.tent would reduce the WUE of *** *** the increase of soil water co.tent,the co.tent of notoginsenoside R_(1) and ginsenoside Rg_(1) did not change significantly,while the co.tent of ginsenoside Rb_(1) and Rd showed a decreasing ***:Soil moisture co.tent significantly affected the water co.sumption of ***,and when it was 56.4% of the maximum water h

关键词： Panax notoginseng(Burk.)F.H.Chen saponins transpiration co.fficient water co.sumption dynamics water use efficiency

Identification of metabolites of Radix Paeoniae Alba extract in rat bile, plasma and urine by ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry

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Journal of pharmaceutical Analysis 2014年第1期4卷 14-25页

作者： Zheng-Wei Chen Ling Tong Shu-Ming Li Dong-Xiang Li Ying Zhang Shui-Ping Zhou Yong-Hong Zhu He Sun Department of pharmaceutical Analysis China Pharmaceutical University tasly R&D Institute Tianjin Tasly Group Co. Ltd. Center of Drug Metabolism and Pharmaco.inetics China Pharmaceutical University

Ultra-performance liquid chromatography co.pled with quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF/MS） was developed to identify the absorbed parent co.ponents and metabolites in rat bile, plasma and urine after oral administration of Radix Paeoniae Alba extract （RPAE）. A total of 65 co.pounds were detected in rat bile, plasma and urine samples, including 11 parent co.pounds and 54 metabolites. The results indicated that glucuronidation, hydroxylation and methylation were the major metabolic pathways of the co.ponents of RPAE. Furthermore, the results of this work demonstrated that UPLC-Q-TOF/MS co.bined with MetaboLynx？ software and mass defect filtering （MDF） co.ld provide unique high throughput capabilities for drug metabolism study, with excellent MS mass accuracy and enhanced MSE data acquisition. With the MSE technique, both precursor and fragment mass spectra can be simultaneously acquired by alternating between high and low co.lision energy during a single chromatographic run.

关键词： Radix Paeoniae Alba Metabolite profiling UPLC-Q-TOF/MS Monoterpene glyco.ides

Stellate porous silica based surface-enhanced Raman scattering system for traceable gene delivery

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Chinese Chemical Letters 2021年第6期32卷 1942-1946页

作者： Lei Liu Xin Du Chemical pharmaceutical Research Center Tasly AcademyTasly Holding Group Co.Ltd.Tianjin 300410China Jiangsu tasly Diyi pharmaceutical co. Ltd.Huaian 223003China School of Chemical Engineering The University of AdelaideAdelaideSA 5005Australia Beijing Key Laboratory for Bioengineering and Sensing Technology Department of Chemistry&Biological EngineeringUniversity of Science&Technology BeijingBeijing 100083China Suzhou Nachuangjia Environmental Technology Engineering co. Ltd.Suzhou 215133China

Numerous nanocarriers have been currently developed for intracellular *** potential cytotoxicity of these very small inorganic nanocarriers has raised great ***,it beco.es of utmost importance to co.duct the intracellular trace of *** many analytical techniques,surface enhanced Raman scattering(SERS)method is one of the current state-of-the-art techniques for cell visualization and *** this work,a novel stellate porous silica based gene delivery system has been designed for SERS trace purpose.A stellate porous silica nanoparticle modified with many small Au nanoparticles is designed to replace co.mon metallic SERS *** results show that the designed system not only co.ld deliver si RNA into cells for therapy,but also co.ld realize SERS trace with high sensitivity and non-invasive *** co.structed delivery system has co.siderable potential to trace the dynamic gene delivery in living cells.

关键词： Stellate porous silica Au nanoparticles Surface-enhanced Raman scattering SERS trace Gene delivery

Protective effect of the extract of Yi-Qi-Fu-Mai preparation on hypoxia-induced heart injury in mice

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Chinese Journal of Natural Medicines 2016年第6期14卷 401-406页

作者： FENG Ya-Qian JU Ai-Chun LIU Chun-Hua WANG Ting YU Bo-Yang QI Jin State Key Laboratory of Natural Medicines China Pharmaceutical University Jiangsu Key Laboratory of TCM Evaluation and Translational Research China Pharmaceutical University Department of Technology Development Tian Jin Tasly Pride Pharmaceutical Co. Ltd.

Yi-Qi-Fu-Mai(YQFM) is extensively used clinically to treat cardiovascular diseases in China. To explore the anti-hypoxia effect of the extract of YQFM preparation(EYQFM), the EYQFM(1.4, 2.8, and 5.5 g·kg-1·d-1) was assessed for its heart-protective effect in a chronic intermittent hypoxia(CIH) animal model(oxygen pressure 7%-8%, 20 min per day) for 28 days of treatment. Betaloc(0.151 6 g·kg^(-1)·d^(-1)) was used as a positive co.trol. The histopathological analyses of heart in CIH mice were co.ducted. Several cardiac state parameters, such as left ventricular ejection fractions(EF), stroke volume(SV), expression of creatine kinase(CK), lactate dehydrogenase(LDH), superoxide dismutase(SOD), and malondialdehyde(MDA) were measured. The results showed that treatment with EYQFM markedly reversed swelling of the endothelial cells and vacuolization in the heart when co.pared with the model group. Further study demonstrated that EYQFM significantly improved ventricular myocardial co.tractility by increasing EF and SV. In addition, EYQFM inhibited the activity of CK, LDH, decreased the level of MDA and improved SOD activity. The results demonstrated that EYQFM significantly improved the tolerability of myocardium to hypoxia and ameliorated the cardiac damage in the CIH model.

关键词： Extract of YQFM preparation Chronic intermittent hypoxia Cardiac damage

Sulfite as the substrate of C-sulfonate metabolism ofα,β-unsaturated carbonyl co.taining andrographolide:analysis of sulfite in rats'intestinal tract and the reaction kinetics of andrographolide with sulfite

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Chinese Journal of Natural Medicines 2021年第9期19卷 706-712页

作者： HUO Zhi-Peng FENG Xin-Chi WANG Yu TIAN Yu-Ting QIU Feng School of Chinese Materia Medica and State Key Laboratory of Component-based Chinese MedicineTianjin University of Traditional Chinese MedicineTianjin 301617China ~TCM Research Center Tasly AcademyTasly Holding Group Co.Ltd.Tianjin 300402China State Key Laboratory of Critical Technology in Innovative Chinese Medicine Tasly Pharmaceutical Co.Ltd.Tianjin 300402China Institute of Pharmacy China Pharmaceutical UniversityNanjing 210009China Institute of pharmaceutical Science and Technology Tianjin UniversityTianjin 300072China

One-sixth of the currently known natural products co.tainα,β-unsaturated carbonyl *** previous studies reported a rare C-sulfonate metabolic *** groups were linked to theβ-carbon ofα,β-unsaturated carbonyl-based natural co.pounds through this ***,the mechanism of this type of metabolism is still not fully understood,especially whether it is formed through enzyme-mediated biotransformation or direct sulfite *** this work,the enzyme-mediated and non-enzymatic pathways were ***,the sulfite co.tent in rat intestine was determined by LC-MS/*** results showed that the amount of sulfite in rat intestinal co.tents was from 41.5 to 383μg·g^(-1),whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation(20μg·g^(-1)).Seco.d,the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions(pH 6-8)was *** half-lives of andrographolide ranged from minutes to *** was suggested that the C-sulfonate reaction of andrographolide was very ***,the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-co.jugate andrographolide were incubated with the rat small intestine co.tents or sulfite,indicating that the sulfite amount in rat intestine co.tents was high enough to react with andrographolide,which assisted a significant portion of andrographolide ***,the co.parison of andrographolide metabolite profiles among liver homogenate(with NADPH),liver S9(with NADPH),small intestine co.tents homogenate(with no NADPH),and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic *** summary,sulfite can serve as a substrate for C-sulfonate metabolism,and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of co.pounds co.tainingα,β-unsaturated carbonyl moie

关键词： Sulfite C-Sulfonate metabolites α,β-Unsaturated carbonyl Reaction kinetics Andrographolide Non-enzymatic

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active co.ponents identification

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Chinese Journal of Natural Medicines 2023年第6期21卷 459-480页

作者： YANG Fengge ZHANG Sihao TIAN Danmei ZHOU Guirong TANG Xiyang MIAO Xinglong HE Yi YAO Xinsheng TANG Jinshan Institute of Traditional Chinese Medicine and Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of ChinaJinan UniversityGuangzhou 510632China State Key Laboratory of co.e Technology in Innovative Chinese Medicine Tasly Pharmaceutical Group Co.Ltd.Tianjin 300410China tasly pharmaceutical Group co. Ltd.Tianjin 300410China

Chang-Kang-Fang(CKF)formula,a Traditional Chinese Medicine(TCM)prescription,has been widely used for the treatment of irritable bowel syndrome(IBS).However,its potential material basis and underlying mechanism remain ***,this study employed an integrated approach that co.bined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS)with network pharmaco.ogy to systematically characterize the phytochemical co.ponents and metabolites of CKF,as well as elucidating its underlying *** this co.prehensive analysis,a total of 150 co.ponents were identified or tentatively characterized within the CKF ***,six N-acetyldopamine oligomers from Cicadae Periostracum and eight resin glyco.ides from Cuscutae Semen were characterized in this formula for the first ***,149 xenobiotics(58 prototypes and 91 metabolites)were detected in plasma,urine,feces,brain,and intestinal co.tents,and the in vivo metabolic pathways of resin glyco.ides were elaborated for the first ***,network pharmaco.ogy and molecular docking analyses revealed that alkaloids,flavonoids,chromones,monoterpenes,N-acetyldopamine dimers,p-hydroxycinnamic acid,and Cus-3/isomer might be responsible for the beneficial effects of CKF in treating IBS,and CASP8,MARK14,PIK3C,PIK3R1,TLR4,and TNF may be its potential *** disco.eries offer a co.prehensive understanding of the potential material basis and clarify the underlying mechanism of the CKF formula in treating IBS,facilitating the broader application of CKF in the field of medicine.

关键词： Chang-Kang-Fang Chemical profile Metabolites profile UPLC-Q-TOF/MS Network pharmaco.ogy Molecular docking

ITS2 barco.ing DNA region co.bined with high resolution melting(HRM) analysis of Hyoscyami Semen, the mature seed of Hyoscyamus niger

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Chinese Journal of Natural Medicines 2016年第12期14卷 898-903页

作者： XIONG Chao HU Zhi-Gang TU Yuan LIU He-Gang WANG Ping ZHAO Ming-Ming SHIi Yu-Hua WU Lan SUN Wei CHEN Shi-Lin co.lege of Pharmacy Hubei University of Chinese Medicine Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Traditional Chinese Medicine Resources Research Center Tianjin Tasly Pharmaceutical Co. Ltd.

Hyoscyami Semen, the mature dried seed of Hyoscyamus niger L., has long been used as a traditional Chinese medicine to treat human diseases. Hyoscyami Semen is found in local markets in China. In markets, sellers and buyers co.monly inadvertently mix the seeds of H. niger with the seeds of related species such as Hygrophila salicifolia(Vahl) Nees, Astragalus co.planatus R. Br., Cuscuta australis R. Br., Cuscuta chinensis Lam., and Impatiens balsamina L. because of their similar morphologies or similar names. Thus, developing a reliable method for discriminating H. niger seeds from its adulterants is necessary to reduce co.fusion and ensure the safe use of Hyoscyami Semen. The present study was designed to evaluate the efficiency of high-resolution melting analysis co.bined with DNA barco.ing(Bar-HRM) with internal transcribed spacer 2 to discriminate H. niger. Our results show that Bar-HRM successfully identified the adulterants and detected the proportion of H. niger DNA extract within an admixture. In particular, HRM detected H. niger DNA extract in A. co.planatus DNA extract at co.centrations as low as 1%. In co.clusion, the Bar-HRM method developed in the present study for authenticating H. niger is rapid and co.t-effective. It can be used in the future to guarantee the purity of Hyoscyami Semen for the clinical use.

关键词： Hyoscyami Semen Bar-HRM Identification Clinical safe medication