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Effect of Chinese Patent Medicine Naodesheng against Repeated Transient Global Cerebral Ischemia in Mice

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Chinese Herbal Medicines 2015年第4期7卷 339-343页

作者： Chun-hua Hao Wen-gong Xi Hai-juan Zheng Wei-ting Wang Zhuan-you Zhao State Key Laboratory of Pharmacokinetics and pharmacodynamics Tianjin Institute of Pharmaceutical Research Tianjin Medical University

Objective To investigate the therapeutic effect and possible mechanisms of Chinese ptent medicine Naodesheng（NDS） on repeated transient global cerebral ischemia（GCI） in mice. Methods The repeated transient GCI mice were induced by bilateral carotid arteries ligation, and were randomly divided into model group, Sham group without arteries ligation, NDS groups（1.25 and 2.5 g/kg） and positive control（vinpocetine 3.1 mg/kg, VP） group. After oral administration once daily for successive 7 d, the transient GCI was induced. The degree of neurological deficit, histological changes, and neurons loss in the hippocampus were evaluated. In order to investigate the possible mechanisms, the oxidative stress and inflammatory factor were measured after 24 h of GCI. Comparison among multiple groups was performed with one-way analysis of variance（ANOVA）. Results NDS could significantly alleviate the neurological function impairment, histological injury, and neurons loss, increase the superoxide dismutase（SOD） activity, decrease the content of malondialdehyde（MDA）, and reduce inflammatory factor in the ischemic brain tissue. Conclusion NDS could significantly reduce brain injury induced by global ischemia, and its mechanism is closely associated with anti-oxidation and anti-inflammation.

关键词： Naodesheng repeated transient global cerebral ischemia vascular dementia

Broussonin E suppresses LPS-induced inflammatory response in macrophages via inhibiting MAPK pathway and enhancing JAK2-STAT3 pathway

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Chinese Journal of Natural Medicines 2019年第5期17卷 372-380页

作者： HUANG Shao-Peng GUAN Xin KAI Guo-Yin XU Ya-Zhou XU Yuan WANG Hao-Jie PANG Tao ZHANG Lu-Yong LIU Ying School of Basic Medicine Center for Drug Screening and Pharmacodynamics Evaluation School of Pharmacy Guangdong Pharmaceutical University College of Pharmaceutical Science Zhejiang Chinese Medical University Jiangsu Key Laboratory of Drug Screening State Key Laboratory of Natural Medicines China Pharmaceutical University School of Medicine and Life Sciences Nanjing University of Chinese Medicine

Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks of Broussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1(Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase(JAK) 2, signal transducer and activator of transcription(STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.

关键词： Broussonin E Macrophage polarization Inflammation Janus kinase 2 Signal transducer and activator of transcription 3

Altered integrity of hepatocyte tight junctions in rats with triptolide-induced cholestasis

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Chinese Journal of Natural Medicines 2021年第3期19卷 188-194页

作者： HUANG Shan LIU Li MEI Hui-Fang ZHANG Qian-Wen ZHANG Xi XU Xiao-Ting WANG Xin-Zhi HUANG Xin WANG Tao JIANG Zhen-Zhou ZHANG Lu-Yong SUN Li-Xin Jiangsu Key Laboratory of Drug Screening China Pharmaceutical UniversityNanjing 210009China Center for Drug Research and Development Guangdong Pharmaceutical UniversityGuangzhou 510006China Jiangsu Center for pharmacodynamics Research and Evaluation China Pharmaceutical UniversityNanjing 210009China Changde Vocational Technology College Changde 415000China

Triptolide(TP),an active component of Tripterygium wilfordii Hook.f.(TWHF),has been widely used for centuries as a traditional Chinese ***,the clinical application of TP has been restricted due to multitarget toxicity,such as *** this study,28 days of oral TP administration(100,200,or 400μg·kg^(-1)·d^(-1))induced the occurrence of cholestasis in female Wistar rats,as evidenced by increased serum levels ofγ-glutamyl transpeptidase(γ-GGT),alkaline phosphatase(ALP)and hepatic total bile acids(TBAs).In addition,the heptocyte polarity associated with the strcture of tight junctions(TJs)was disrupted in both rats and sandwich-cultured primary *** revealed decreased expression of the TJ-associated proteins occludin,claudin^(-1),and zonula occludens protein(ZO^(-1)),and downregulated m RNA levels of these TJs was also detected by real-time *** immunofluorescence analysis showed abnormal subcellular localization of occludin,claudin^(-1) and ZO^(-1),which was also confirmed by transmission electron ***,the concentration of FITC-dextran,a marker of paracellular penetration,was found to increase rapidly in bile increased rapidly(within 6 minutes)after treatment with TP,which indicated the functional impairment of *** together,these results suggest that the administration of TP for 28 consecutive days to rats could induce cholestatic injury in the liver,and the increased paracellular permeability might play an important role in these pathological changes.

关键词： Triptolide Cholestatic injury Tight junction Sandwich-cultured primary hepatocytes

In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells

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Neural Regeneration Research 2015年第12期10卷 2011-2017页

作者： Yan Wang Ning Wang Biao Cai Guang-yun Wang Jing Li Xing-xing Piao Key Laboratory of Xin’an Medicine Ministry of Education Institute for pharmacodynamics and Safety Evaluation of Chinese Medicine Anhui Academy of Chinese College of Pharmacy Anhui University of Chinese Medicine

Drugs for the treatment and prevention of nervous system diseases must permeate the bloodbrain barrier to take *** vitro models of the blood-brain barrier are therefore important in the investigation of drug permeation ***,to date,no unified method has been described for establishing a blood-brain barrier ***,we modified an in vitro model of the blood-brain barrier by seeding brain microvascular endothelial cells and astrocytes from newborn rats on a polyester Transwell cell culture membrane with 0.4-μm pores,and conducted transepithelial electrical resistance measurements,leakage tests and assays for specific bloodbrain barrier *** show that the permeability of our model is as low as that of the bloodbrain barrier in *** model will be a valuable tool in the study of the mechanisms of action of neuroprotective drugs.

关键词： nerve regeneration blood-brain barrier astrocytes brain microvascular endothelial cells permeability co-culture Transwell chamber neural regeneration

Relationship of quantitative structure and pharmacokinetics in fluoroquinolone antibacterials

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World Journal of Gastroenterology 2007年第17期13卷 2496-2503页

作者： Die Cheng Wei-Ren Xu Chang-Xiao Liu Department of Pharmaceutical Engineering Schoolof Chemical Engineering and Technology Tianjin UniversityTianjin 300072 China National KeyLaboratory of Pharmacokinetics and pharmacodynamics TianjinInstitute of Pharmaceutical Research Tianjin 300193 China

AIM： To study the relationship between quantitative structure and pharmacokinetics （QSPkR） of fluorocluinolone antibacterials.METHODS： The pharmacokinetic （PK） parameters of oral fluoroquinolones were collected from the literature. These pharmacokinetic data were averaged, 19 compounds were used as the training set, and 3 served as the test set. Genetic function approximation （GFA） module of Cerius2 software was used in QSPkR analysis.RESULTS： A small volume and large polarizability and surface area of substituents at C-7 contribute to a large area under the curve （AUC） for fluoroquinolones. Large polarizability and small volume of substituents at N-1 contribute to a long half life elimination.CONCLUSION： QSPkR models can contribute to some fluoroquinolones antibacterials with excellent pharmacokinetic properties.

关键词： Quantitative structure pharmacokinetic relationship Genetic function approximation Fluoro-quinolones Elimination half life

Sensitization Properties of Propolis and Balsam of Peru in Guinea Pig Maximization Test(GPMT)

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Food and Nutrition Sciences 2017年第7期8卷 714-724页

作者： Katarzyna Basista-Soltys Barbara Filipek Monika Zadrozna Barbara Nowak Agata Pietrzycka Grzegorz Kazek Department of pharmacodynamics Medical College of Jagiellonian UniversityKrakowPoland Department of Pharmacobiology Medical College of Jagiellonian UniversityKrakowPoland

Introduction: Propolis is used in Poland as an active ingredient of some drugs administered externally, dietary supplements and cosmetics. According to the literature, propolis is a non-toxic and safe substance, although it may cause allergic contact dermatitis. Aim: The aim of this study was to assess the allergenic properties of propolis and Balsam of Peru. Material and methods: The study was conducted according to the OECD Guideline for testing of chemicals-Skin sensitization with use of Guinea pig maximization test (GPMT). Guinea pigs have similar sensitivity to allergens as human body. Sensitization properties of propolis were tested in comparison with sensitization properties of Balsam of Peru because of the possibility of cross-reaction between those two substances. Results: The skin of guinea pigs in the propolis group showed no visible change compared to the control group during the first (48 h) and second observation (72 h). The skin of guinea pigs from Balsam of Peru group showed discrete erythema in only one case at the first observation (8.33% of the animals). During the second observation, no visible changes were observed compared to the control group. Conclusions: Guinea pig maximization test showed no sensitizing properties of propolis and weak sensitizing properties of Balsam of Peru in concentration of 5%.

关键词： Propolis Balsam of Peru Guinea Pig Maximization Test Sensitization Properties Allergic Contact Dermatitis

Neuroprotective effect of Sanqi Tongshuan Tablets on sequelae post-stroke in rats

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Chinese Herbal Medicines 2019年第1期11卷 45-51页

作者： Wei-ting Wang Chun-hua Hao Shao-xiang Zhang Xiang-hua Zhang Feng Guo Shuang-yong Sun Rui Zhang Zhuan-you Zhao Li-da Tang State Key Laboratory of Pharmacokinetics and pharmacodynamics Tianjin Institute of Pharmaceutical Research Kunming Hospital of Traditional Chinese Medicine Kunming Institute of Nephrology

Objective: To identify the therapeutic effect and possible mechanisms of Chinese medicine Sanqi Tongshuan Tablets(SQTS) on sequelae post-stroke in ***: The rat cerebral ischemia sequelae post-stroke models were successfully induced by blocking the middle cerebral artery with electric coagulator after the seventh week and balance beam test ≤ 4. The rats were then received with SQTS(0.5, 1, and 2 g/kg) and Naodesheng(NDS, 1.24 g/kg), Vinpocetine(VP,1.55 mg/kg) for 30 d. The beam-walking test and shuttle test were performed before and after 10, 20, and 30 d of administration. In addition, histopathology changes and GAP-43, GFAP were measured by H&E staining and ***: The model displayed signs of brain damage on motor function, learning and memory function and histopathology. After 30 d of treatment, SQTS at different doses(0.5, 1.0, and 2.0 g/kg) restored the beam-walking scores by 21.7%(P > 0.05), 30.4%(P > 0.05), and 39.1%(P 0.05), 50.0%(P > 0.05), and 75.0%(P < 0.05), respectively. On the other hand, the histological changes were less severe and the GAP-43 expression increased in hippocampal CA1 and cortical ***: SQTS showed therapeutic benefits on sequelae post-stroke in rats, which might be through the pathway of regeneration or neuroplasticity.

关键词： learning and memory motor function rats Sanqi Tongshuan Tablets Sequelae post-strokes

3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C, Nanopore, and RNA sequencing

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3150-3164页

作者： Lina Xu Lianhong Yin Yan Qi Xuemei Tan Meng Gao Jinyong Peng College of Pharmacy Dalian Medical UniversityDalian 116044China Key Laboratory for Basic and Applied Research on pharmacodynamics Substances of Traditional Chinese Medicine of Liaoning Province Dalian Medical UniversityDalian 116044China National-Local Joint Engineering Research Center for Drug Development(R&D)of Neurodegenerative Diseases Dalian Medical UniversityDalian 116044China

The three-dimensional(3D)conformation of chromatin is integral to the precise regulation of gene *** 3D genome and genomic variations in non-alcoholic fatty liver disease(NAFLD)are largely unknown,despite their key roles in cellular function and physiological *** chromosome conformation capture(Hi-C),Nanopore sequencing,and RNA-sequencing(RNA-seq)assays were performed on the liver of normal and NAFLD mice.A high-resolution 3D chromatin interaction map was generated to examine different 3D genome hierarchies including A/B compartments,topologically associated domains(TADs),and chromatin loops by Hi-C,and whole genome sequencing identifying structural variations(SVs)and copy number variations(CNVs)by Nanopore *** identified variations in thousands of regions across the genome with respect to 3D chromatin organization and genomic rearrangements,between normal and NAFLD mice,and revealed gene dysregulation frequently accompanied by these *** target genes were identified in NAFLD,impacted by genetic rearrangements and spatial organization *** data provide a high-resolution 3D genome interaction resource for NAFLD investigations,revealed the relationship among genetic rearrangements,spatial organization disruption,and gene regulation,and identified candidate genes associated with these variations implicated in the pathogenesis of *** newly findings offer insights into novel mechanisms of NAFLD pathogenesis and can provide a new conceptual framework for NAFLD therapy.

关键词： 3D genome Chromatin looping Topologically associated domain Transcriptome Whole-genome sequencing

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

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Chinese Herbal Medicines 2022年第4期14卷 479-493页

作者： Zeyu Li Erwei Hao Rui Cao Si Lin Linghui Zou Tianyan Huang Zhengcai Du Xiaotao Hou Jiagang Deng China ASEAN Joint Laboratory for International Cooperation in Traditional Medicine Research Nanning 530200China Guangxi Scientific Experiment Center of Traditional Chinese Medicine Nanning 530000China Guangxi Key Laboratory of pharmacodynamics of Traditional Chinese Medicine Nanning 530000China

Zedoary tumeric(Curcumae Rhizoma,Ezhu in Chinese)has a long history of application and has great potential in the treatment of liver *** antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic *** order to clarify the specific mechanism of zedoary tumeric against liver cancer,this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer,and then verifies the joint anti liver cancer mechanism of its“pharmacodynamic group”.By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years,we found that pharmacodynamic substances,including curcumol,zedoarondiol,curcumenol,curzerenone,curdione,curcumin,germacrone,β-elemene,can act on multi-target and multi-channel to play an antihepatoma *** example,curcumin can regulate miR,GLO1,CD133,VEGF,YAP,LIN28B,GPR81,HCAR-1,P53 and PI3K/Akt/mTOR,HSP70/TLR4 and NF-κ***/TGF/EMT,Nrf2/Keap1,JAK/STAT and other pathways play an antihepatoma *** pharmacological analysis showed that the core targets of the“pharmacodynamic group”for anti-life cancer are AKT1,EGFR,MAPK8,etc,and the core pathways are neuroactive live receiver interaction,nitrogen metabolism,HIF-1 signaling pathway,*** the same time,by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and“pharmacodynamic group”,it is found that they have great reference significance in target,pathway,biological function,determination of core pharmacodynamic components,formation of core target protein interaction,in-depth research of single pharmacodynamic substance,increasing curative effect and so *** analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and“pharmacodynamic group”in the treatment of liver cancer,this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between

关键词： action mechanism Curcumae Rhizoma liver cancer pharmacodynamic groups pharmacodynamic substances zedoary turmeric