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Synthesis of the tetracyclic core of chlorospermines

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chinese Chemical Letters 2015年第3期26卷 272-276页

作者： Ming Wan Ming Yao Jun-Yu Gong Peng Yang Hua Liu Ang Li school of pharmacy Jiangxi University of Traditional Chinese Medicine State Key Laboratory of Bioorganic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of Sciences

Chlorospermines A and B are biologically interesting acridone natural products and recently isolated from Glycosmis *** report here a convergent approach to construct the tetracyclic core of the natural *** two fragments are assembled together through Sonogashira coupling,and a cis-triene intermediate was prepared by using hydrosilylation/desilylation.A 6p-electrocyclization/aromatization sequence served as the key step of the synthesis,which formed the tetrasubstituted arene motif in one pot.

关键词： convergent sequentially steps assembled biologically filtered arene motif equiv latter

Processing methods and mechanisms for alkaloid-rich chinese herbal medicines:A review

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Journal of Integrative medicine 2021年第2期19卷 89-103页

作者： Ruo-lan Li Qing Zhang Jia Liu Li-ying He Qin-wan Huang Wei Peng Chun-jie Wu school of pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina

The processing of chinese herbal medicine is a form of pharmaceutical technology developed over thousands of years,in order to increase efficiency and decrease toxicity of herbs in traditional chinese medicine(TCM).Herbal processing is essential for safe and effective application of TCM in clinical practice,as it alters the active chemical components and therefore the functions of herbal ***-rich herbal medicines in TCM are commonly processed by cleansing,cutting,processing by dry stir-frying,stir-frying with liquid adjuvants,and processing by water *** addition,commonly used adjuvants for processing alkaloid-rich herbal medicines are river sand,wine,vinegar,brine,honey and herbal *** alkaloid-rich herbal medicines,the main chemical reactions that occur during processing include hydrolysis,oxidation,replacement,decomposition and *** paper aimed to summarize the processing methods and mechanisms for alkaloid-rich chinese herbal medicines,and provide much-needed theoretical support and scientific evidence for understanding those mechanisms and *** on processing methods for alkaloid-rich herbal medicines was collected from classic books of herbal medicine,PhD and MSc dissertations,online scientific databases including PubMed,SciFinder,Scopus,Web of Science,Baidu Scholar and Google *** paper should help to advance our knowledge of the processing mechanisms and aid in the development of processing methods for alkaloid-rich chinese herbal medicines.

关键词： Alkaloids Alkaloid-rich herbal medicines chinese medicine processing

Fructus Zanthoxyli extract improves glycolipid metabolism disorder of type 2 diabetes mellitus via activation of AMPK/PI3K/Akt pathway:Network pharmacology and experimental validation

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Journal of Integrative medicine 2022年第6期20卷 543-560页

作者： Ting Zhang Qing Zhang Wei Zheng Ting Tao Ruo-lan Li Li-yu Wang Wei Peng Chun-jie Wu school of pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina

Objective:This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli(FZ)against type 2 diabetes mellitus(T2DM)based on network pharmacology and experimental ***:Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry,and gas chromatography-mass spectrometry were used to identify the constituents of ***,the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases(including Gene Expression Omnibus database and Swiss Target Prediction online database),and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes(KEGG).Finally,the pathway was verified by in vitro experiments,and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on ***:A total of 43 components were identified from FZ,and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in *** dug component-target network indicated that PPARA,PPARG,PIK3R3,JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of ***,the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase(AMPK)and phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)signaling *** vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in Hep G2 ***,FZ treatment was able to promote the AMPK and PI3K/Akt expressions in Hep G2 ***:Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.

关键词： Fructus Zanthoxyli Zanthoxylum bungeanum Maxim Type 2 diabetes mellitus Network pharmacology Glucose and lipid metabolism Phosphatidylinositol-3-kinase AMPK/PI3K/Akt

Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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chinese Journal of Integrative medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou school of traditional chinese medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

Succinylated whey protein isolate as a sustained-release excipient of puerarin derivative oral tablets:Preparation,optimization and pharmacokinetics

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Asian Journal of Pharmaceutical Sciences 2018年第4期13卷 383-394页

作者： Rui Zhang Yu Zhang Yue Wu Jun Liu Tiantian Ye Shujun Wang Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical University College of traditional chinese medicine Beijing University of Chinese Medicine chinese medicine(traditional chinese medicine Preparation Direction)College of traditional chinese pharmacy Shenyang Pharmaceutical University Department of pharmacy China Pharmaceutical University

This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by optimization of single factor study and Box–Beehnkendesign. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochem-ical properties of S-WPIs dried by different three methods on their flow ability, particle size,morphology and in vitro release behavior were studied. After preparing PR-5 sustained re-lease protein tablets with S-WPIs as the carrier by direct powder compression method, thedrug release were studied in vitro and the oral pharmacokinetics and bioavailability wasevaluated using in vivo dog model. It was observed that concentration of substrate has asignificant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism(protein loss). Comparedwith PR-5 conventional tablet with oral administration, T max value of PR-5 sustained-releaseprotein tablets was approximately 1.58 fold greater than those of the conventional tablets asfurther evidenced by the significantly prolonged MRT and T 1/2. The findings demonstratedthat spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability.

关键词： Whey protein isolate Succinylation Puerarin 5 Sustained drug delivery Pharmacokinetics

Microbial-host-isozyme:a new territory for understanding personalized responses towards drug therapy

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chinese Journal of Natural medicines 2023年第8期21卷 561-562页

作者： LI Mingxiao LI Houkai school of pharmacy Shanghai University of Traditional Chinese MedicineShanghaiChina

Inter-individual responses to medicinal drugs vary widely in clinic,which drives the urgent need of precision medicine for minimizing adverse reactions and maximalizing therapeutic effects among patients[1].In addition to genetic factors,increasing evidence suggests that gut microbiome plays a crucial role in affecting either pharmacodynamics or pharmacokinetics[2].In recent years,at least two ways have been demonstrated through which gut microbiome jointly affects drug metabolism or efficacy with *** is the microbial metabolism on *** et al.[3]systematically studied the direct interaction between microorganisms and *** found that 2/3 of the 271 selected orally administered drugs could be metabolized by at least one *** also verified that 30 enzymes encoded by microorganisms have the ability to transform 20 drugs into 59 candidate *** direct interaction between gut microbiota and drugs,including chemical modification(such as sulfasalazine[4]),inactivation(such as digoxin[5])or changes in toxicity(such as irinotecan[6]).Another way is the bioaccumulation of drugs in gut bacteria that alters drug availability and ***ünemann et al.[7]investigated the depletion of 15 drugs with different structures by 25 representative *** study reveals 70 interactions between bacteria and drugs,of which 29 have not been reported in previous studies,and more than half of the new interactions can be attributed to bioaccumulation.

关键词： Inter-individual responses Drug metabolism Microbial-host-isozyme

Tumor cell membrane-coated continuous electrochemical sensor for GLUT1 inhibitor screening

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Journal of Pharmaceutical Analysis 2023年第6期13卷 673-682页

作者： Jiaqian Zhao Yuqiao Liu Ling Zhu Junmin Li Yanhui Liu Jiarui Luo Tian Xie Dajing Chen school of pharmacy Hangzhou Normal UniversityHangzhou310000China Innovation Research Institute of traditional chinese medicine Shanghai University of Traditional Chinese MedicineShanghai201203China

Glucose transporter 1(GLUT1)overexpression in tumor cells is a potential target for drug therapy,but few studies have reported screening GLUT1 inhibitors from natural or synthetic *** current analysis techniques,it is difficult to accurately monitor the GLUT1 inhibitory effect of drug molecules in *** developed a cell membrane-based glucose sensor(CMGS)that integrated a hydrogel electrode with tumor cell membranes to monitor GLUT1 transmembrane transport and screen for GLUT1 inhibitors in traditional chinese medicines(TCMs).CMGS is compatible with cell membranes of various origins,including different types of tumors and cell lines with GLUT1 expression knocked down by small interfering RNA or small *** on CMGS continuous monitoring technique,we investigated the glucose transport kinetics of cell membranes with varying levels of GLUT1 *** used CMGS to determine the GLUT1-inhibitory effects of drug monomers with similar structures from Scutellaria baicalensis and catechins *** were consistent with those of the cellular glucose uptake test and molecular-docking *** could accurately screen drug molecules in TCMs that inhibit GLUT1,providing a new strategy for studying transmembrane protein-receptor interactions.

关键词： Glucose transporter 1 inhibitor Electrochemical sensor Drug screen traditional chinese medicine

The potential of herbal drugs to treat heart failure:The roles of Sirt1/AMPK

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Journal of Pharmaceutical Analysis 2024年第2期14卷 157-176页

作者： Tao Zhang Lei Xu Xiaowei Guo Honglin Tao Yue Liu Xianfeng Liu Yi Zhang Xianli Meng State Key Laboratory of Southwestern chinese medicine Resources Innovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China College of pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China school of Ethnic medicine Chengdu University of Traditional Chinese MedicineChengdu611137China Meishan Hospital of Chengdu university of traditional chinese medicine MeishanSichuan620032China

Heart failure(HF)is a highly morbid syndrome that seriously affects the physical and mental health of patients and generates an enormous socio-economic *** addition to cardiac myocyte oxidative stress and apoptosis,which are considered mechanisms for the development of HF,alterations in cardiac energy metabolism and pathological autophagy also contribute to cardiac abnormalities and ultimately *** information regulator 1(Sirt1)and adenosine monophosphate-activated protein kinase(AMPK)are nicotinamide adenine dinucleotide(NAD+)-dependent deacetylases and phosphorylated kinases,*** play similar roles in regulating some pathological processes of the heart through regulating targets such as peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α),protein 38 mitogen-activated protein kinase(p38 MAPK),peroxisome proliferator-activated receptors(PPARs),and mammalian target of rapamycin(mTOR).We summarized the synergistic effects of Sirt1 and AMPK in the heart,and listed the traditional chinese medicine(TCM)that exhibit cardioprotective properties by modulating the Sirt1/AMPK pathway,to provide a basis for the development of Sirt1/AMPK activators or inhibitors for the treatment of HF and other cardiovascular diseases(CVDs).

关键词： Heart failure Silent information regulator 1 Adenosine monophosphate-activated protein kinase traditional chinese medicine

Making polymer fibers strong and tough simultaneously

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Science China Materials 2020年第3期63卷 481-482页

作者： Wenhui Xu Yichun Ding school of pharmacy Jiangxi University of Traditional Chinese MedicineNanchang 330004China Fujian Institute of Research on the Structure of Matter Chinese Academy of SciencesFuzhou 350002China

It has long been a great challenge to prepare materials with integrated merits of high strength,high modulus,high toughness,and light weight for structural material applications(e.g.,aircrafts,automobiles).High strength representing a good resistance to deformation usually requires the material have a rigid/hard molecular structure,whereas high toughness representing a good resistance to fracture typically originates from a soft/flexible molecular ***,the trade-off between the rigid and flexible components in a molecule usually leads to an intrinsic conflict between high strength and high toughness[1].It is more intuitively in the typical stressstrain curves,where the integrated area of a tensile curve can be calculated for the ***,the attainment of high toughness needs not only high strength but also high tensile strain.

关键词： toughness strength representing