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Asian Pacific Journal of Tropical Medicine 2017年第1期10卷 47-51页

作者： Zhong Han Xia-Ling Lei Hong Zhang Lu Liu Zhi-Sen Chen Wei Yang Zhao-Rong Lun School of Life Sciences Sun Yat-sen UniversityGuangzhou 510275China Guangdong Key Laboratory of Animal Conservation and Resource Utilization Guangdong Public Laboratory of Wild Animal Conservation and UtilizationGuangdong Institute of Applied Biological Resources Guangdong Lewwin pharmaceutical Research Institute Co. Ltd.Guangzhou 510990China

Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD ***: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.

关键词： Forsythin Acute toxicity Sub-chronic toxicity Safety

Establishment of organoid models based on a nested array chip for fast and reproducible drug testing in colorectal cancer therapy

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Bio-Design and Manufacturing 2022年第4期5卷 674-686页

作者： Yancheng Cui Rongrong Xiao Yushi Zhou Jianchuang Liu Yi Wang Xiaodong Yang Zhanlong Shen Bin Liang Kai Shen Yi Li Geng Xiong Yingjiang Ye Xiaoni Ai State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Gastrointestinal Surgery Peking University People’s HospitalBeijing 100044China Beijing Daxiang Biotech Co. Ltd.Beijing 100195China Merck Innovation Hub(Guangdong)Co. Ltd.Guangzhou 510005China

The conventional microwell-based platform for construction of organoid models exhibits limitations in precision oncology applications because of low-speed growth and high variability. Here, we established organoid models on a nested array chip for fast and reproducible drug testing using 50% matrigel. First, we constructed mouse small intestinal and colonic organoid models. Compared with the conventional microwell-based platform, the mouse organoids on the chip showed accelerated growth and improved reproducibility due to the nested design of the chip. The design of the chip provides miniaturized and uniform shaping of the matrigel that allows the organoid to grow in a concentrated and controlled manner. Next, a patient-derived organoid(PDO) model from colorectal cancer tissues was successfully generated and characterized on the chip. Finally, the PDO models on the chip, from three patients, were implemented for high-throughput drug screening using nine treatment regimens. The drug sensitivity testing on the PDO models showed good quality control with a coefficient of variation under 10% and a Z’ factor of more than 0.7. More importantly, the drug responses on the chip recapitulate the heterogeneous response of individual patients, as well as showing a potential correlation with clinical outcomes. Therefore,the organoid model coupled with the nested array chip platform provides a fast and reproducible means for predicting drug responses to accelerate precise oncology.

关键词： Organoid on chip Patient-derived organoids Precise oncology Colorectal neoplasm Drug screening

Evaluation of a granulated formula for the nerve root type and vertebral artery type of cervical spondylosis：a multicenter,single-blind,randomized,controlled,phase Ⅲ clinical trial

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Journal of Traditional Chinese Medicine 2017年第2期37卷 193-200页

作者： Luo Xiaodong Wang Peng Li Zhe Liang De Huang Feng Liu Jinwen Chen Xinyu Hu Guoheng Fang Suting Zhang Huajian Department of Encephalopathy TheSecond Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510370 China Faculty of Chinese Medicine Macao Universityof Science and Technology Macao 999078 China Department of Orthopaedics TheFirst Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou 510405 China Department of Orthopaedics The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120 China Department of Cardiology The First AffiliatedHospital of Hunan University of Chinese Medicine Changsha 410007 China Department of Encephalopathy The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410007 China Department of Orthopaedics Hubei Provincial Academy of Chinese Medicine Wuhan 430074 China Research Institution Shineway Pharmaceutical Group Ltd. Shijiazhuang 051430 China

OBJECTIVE:To evaluate the effectiveness and safety of cervical spondylosis formula granules in reducing the symptoms of patients with the nerve root type and the vertebral artery type of cervical ***:This was a multicenter, single-blind,randomized, controlled *** April 2002 to November 2003, 499 patients were randomly assigned to either the treatment or the control *** treatment group was orally administered granules prepared with a formula for cervical spondylosis, while the control group was given Jingfukang *** treatment course was 1 month for both ***:In patients with the nerve root type of cervical spondylosis, the total effect rate in the treatment group(87.21%) was significantly higher than that in the control group(80.70%, P 0.05).After the treatment period in both groups,the treatment group had a significantly greater rate of resolution of weakness of the waist and knees than the control group(P < 0.05).CONCLUSION:The cervical spondylosis formula granules significantly improve numbness, muscle strength, and fatigue, and reduce pain in patients with the nerve root type of cervical spondylosis,and improve the weakness of the waist and knees in patients with the vertebral artery type of cervical spondylosis.

关键词： Spondylosis Deficiency of liver and kidney Qi-deficiency blood stasis Jingfukang granules Randomized controlled trial

Two cardenolide glycosides from the seed fairs of Asclepias curassavica and their cytotoxic activities

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Chinese Journal of Natural Medicines 2022年第03期 202-209页

作者： JI Ai-Jia MA Qing KONG Mu-Yan LI Le-Yan CHEN Xin-Lian LIU Zhong-Qiu WU Jin-Jun ZHANG Rong-Rong Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine China Resources Sanjiu Medical & pharmaceutical Co. Ltd. School of pharmaceutical Sciences Sun Yat-Sen University

Two cardenolide glycosides, corotoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside](1) and coroglaucigenin 3-O-[β-D-glucopyranosyl-(1→4)-6-deoxy-β-D-glucopyranoside](2), were isolated from the seed fairs of Asclepias curassavica. The structures of 1-2 were determined based on the combination of the analysis of their MS, NMR spectroscopic data and acid hydrolysis. The inhibitory effects of compounds 1 and 2 on human colorectal carcinoma cells(HCT116), non-small cell lung carcinoma cells(A549) and hepatic cancer cells(SMMC-7721) were evaluated. The results showed that both compounds 1 and 2 significantly inhibited the viability, proliferation, and migration of A549, HCT116 and SMMC-7721 cells, suggesting that compounds 1 and 2 can be applied in the treatment of lung, colon and liver cancers in clinical practice. This study may not only provide a scientific basis for clarifying the active ingredients in A. curassavica, but also help to understand its antitumor activity, which can promote the application of A. curassavica in clinical treatment of various cancers.

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Systematic screening procedure and innovative energy-saving design for ionic liquid-based extractive distillation process

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Frontiers of Chemical Science and Engineering 2023年第1期17卷 34-45页

作者： Tuanjie Shen Liumei Teng Yanjie Hu Weifeng Shen Anhui XinShiJi pharmaceutical Co. Ltd.Hefei 230000China School of Materials Science and Engineering Chongqing University of Arts and SciencesChongqing 402160China School of Materials and Energy Guangdong University of TechnologyGuangzhou 510006China School of Chemistry and Chemical Engineering Chongqing UniversityChongqing 400044China

In the traditional extractive distillation process,organic solvents are often used as ***,environmental influence and high energy-consumption are significant problems in industrial *** this study,a systematic screening strategy and innovative energy-saving design for ionic liquid-based extractive distillation process was *** innovative energy-saving design focused on the binary minimum azeotrope mixtures isopropanol and ***,environmental impact and physical properties(e.g.,melting point and viscosity)of 30 ionic liquids were investigated.1-Ethyl-3-methyl-imidazolium dicyanamide and 1-butyl-3-methyl-imidazolium dicyanamide were selected as candidate *** analysis of these two ionic liquids was further performed via residue curve maps,isovolatility line and temperature *** innovative ionic liquid-based extractive distillation process combining distillation column and stripping column was designed and optimized with the objective function of minimizing the total annualized *** results demonstrate that the total annualized cost was reduced by 19.9%with 1-ethyl-3-methyl-imidazolium dicyanamide as the entrainer and by 24.3%with 1-butyl-3-methyl-imidazolium dicyanamide,compared with that of dimethyl *** method proposed in this study is conducive to the green and sustainable development of extractive distillation process.

关键词： ionic liquid entrainer screening feasibility analysis extractive distillation

Yang xin shi tablet enhances adaptability to exercise training by relieving statin-induced skeletal muscle injury

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Chinese Medical Journal 2020年第18期133卷 2266-2268页

作者： Ruo-Ming Wu Bing Jiang Hui Li Wen-Zhen Dang Cong Zhang Xiao-Zheng Zhong Yi Hong Guan Ye Xiao-Yan Shen Central Research Institute Shanghai Pharmaceuticals Holding Co.Ltd.Shanghai 200120China Department of Pharmacology School of PharmacyFudan UniversityShanghai 200120China Department of Pharmacology of Chinese Materia Medica School of Traditional Chinese MedicineGuangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China SPH Qingdao Growful pharmaceutical Co. Ltd.QingdaoShandong 266510China

To the Editor:Widely used statins lower the risk of death from cardiovascular ***,statin-associated skeletal muscle complaints hinder their clinical application to some *** xin shi tablet(YXST),a traditional Chinese medicine formula,can effectively improve the clinical symptoms of patients with cardiovascular diseases when combined with conventional ***,the synergistic effects of YXST combined with a statin and the potential mechanisms remain ***,exploring the effects and mechanisms of YXST in improving statin-induced muscle injury can be beneficial for the exercise rehabilitation and prognosis of patients with cardiovascular disease.

关键词： cardiovascular skeletal drugs

Two new phenolic amides from Allium chinense

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Chinese Herbal Medicines 2023年第4期15卷 603-606页

作者： Xiaoqing Li Shikai Yan Jihong Lu Rui Wang Xianpeng Ma Xue Xiao Yan Zhang Huizi Jin Department of Natural Product Chemistry School of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Institute of Chinese Medicinal Sciences Guangdong Pharmaceutical UniversityGuangzhou 510006China Guizhou Jingcheng pharmaceutical Co. Ltd.Guiyang 550200China

Objective: To isolate the phenolic amides from the dried bulbs of Allium chinense and investigate their myocardium protective ***: The chemical constituents were isolated and purified by combining with silica gel column,Sephadex LH-20 column, HPLC and other chromatography techniques. Their structures were elucidated by NMR techniques and mass spectrometry. The isolated compounds were evaluated to determine their protective effect for myocardium cells in ***: Two new phenolic amides, namely, alichinemide Ⅰ(1) and alichinemide Ⅱ(2), and six konwn amides were isolated from the dried bulbs of A. chinense. The structures of compounds 3–8 were identified as 3-indolcarbaldehyde(3), 1-(2-aminophenyl)urea(4), 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), N-trans-feruloyltyramine(6), N-trans-p-coumaroyltyramine(7), and N-(3,4-dimethoxyphenethyl) acetamide(8). Compound 3(50 μmol/L) showed significant inhibitory effect on the damage of H9c2 myocardial cells induced by H2O2in ***: Compounds 1 and 2 were new phenolic amides. Compound 3 could be one of the potential myocardium protective constituents of A. chinense.

关键词： alichinemideⅠ alichinemideⅡ Allium chinense 3-indolcarbaldehyde myocardium protective activities phenolic amides

Separation of Five Quinolone Alkaloids from Fruits of Evodia rutaecarpa by High-speed Counter-current Chromatography

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Chinese Herbal Medicines 2014年第1期6卷 47-52页

作者： Pei-ting Zhang Bi-yan Pan Qiong-feng Liao Mei-cun Yao Xin-jun Xu Jin-zhi Wan Dan Liu Zhi-yong Xie School of pharmaceutical Sciences Sun Yat-sen University guangzhou Baiyun Shan Ming Xing pharmaceutical Co. Ltd. College of Chinese Traditional Medicine Guangzhou University of Chinese Medicine

Objective To develop a suitable method for the large-scale separation of quinolone alkaloids from the fruits of Evodia rutaecarpa by high-speed counter-current chromatography （HSCCC）. Methods Two solvent systems were developed for the separation method. The upper phase was used as the stationary phase, and the lower phase was used as the mobile phase at 35 oCwith the flow rate of 2 mL/min and rotation speed of 855 r/min. Results Using the described method, 1-methyl-2-undecyl- 4（1H）-quinoione （1）, evocarpine （2）, 1-methy-2-[（6Z,9Z}]-6,9-pentade-cadienyl-4- （1H）-quinolone （3）, dihydroevocarpine （4）, and the mixture （5） of 1-methyl-2-[（z^- 10-pentadecenyl]-4（1H）-quinolone （Va） and 1 -methyl-2-[（Z^-6-pentadecenyl]- 4（1H）-quinolone （Vb） could be isolated from a petroleum ether extract. They were identified by 1H-NMR, ~3C-NMR, and MS/MS, and the purities were 94.3%, 95.2%, 96.8%, 98.3%, and 96.8%, respectively. Conclusion Five quinolone alkaloids from the fruits of E. rutaecarpa could be systematically isolated and purified using HSCCC. The presented method is simple and efficient with good potentials on the preparation of reference substances, especially on the quality control of Chinese materia medica.

关键词： dihydroevocarpin evocarpine Evodia rutaecarpa high-speed counter-currentchromatography quinolone alkaloids

The mechanisms of melanogenesis inhibition by glabridin:molecular docking,PKA/MITF and MAPK/MITF pathways

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Food Science and Human Wellness 2023年第1期12卷 212-222页

作者： Chunxing Pan Xiaoying Liu Yating Zheng Zejun Zhang Yongliang Li Biao Che Guangrong Liu Lanyue Zhang Changzhi Dong Haji Akber Aisa Zhiyun Du Zhengqiang Yuan School of Biomedical and pharmaceutical Sciences Guangdong University of TechnologyGuangzhou 510006China Infinitus(China)Company ltd. Guangzhou 510663China Foshan Allen Conney Biological Technology Co. Ltd.Foshan 528225China UniversitéParis Diderot Sorbonne Paris CitéITODYSUMR 7086 CNRSFrance The Key Laboratory of Plant Resources and Chemistry of Arid Zone Xinjiang Technical Institute of Physics and ChemistryChinese Academy of SciencesÜrümqi 830011China

Glabridin is the main ingredient of hydrophobic fraction in licorice extract and has been shown to have anti-melanogenesis activity in ***,the underlying mechanism(s)remain not completely *** aim of this study is thus to elucidate the possible mechanisms related to the melanogenesis suppression by glabridin in cultured B16 murine melanoma cells and in UVA radiation induced hyperpigmentation model of BALB/c mice as *** docking simulations revealed that between catalytic core residues and the *** treatment by glabridin significantly downregulated both transcriptional and/or protein expression of melanogenesis-related factors including melanocyte stimulating hormone receptor(MC1R),microphthalmia-associated transcription factor(MITF),tyrosinase(TYR),TYR-related protein-1(TRP-1)and TRP-2 in B16 *** PKA/MITF and MAPK/MITF signaling pathways were found to be involved in the suppression of melanogenesis by glabridin in B16 *** in vivo glabridin therapy significantly reduced hyperpigmentation,epidermal thickening,roughness and inflammation induced by frequent UVA exposure in mice skins,thus beneficial for skin *** data further look insights into the molecular mechanisms of melanogenesis suppression by glabridin,rationalizing the application of the natural compound for skin healthcare.

关键词： Glabridin Melanogenesis Molecular docking PKA/MITF pathway MAPK/MITF pathway

Yixin Ningshen Tablet Alleviates Comorbidity of Myocardial Infarction and Depression by Enhancing Myocardial Energy Metabolism and Increasing Availability of Monoamine Neurotransmitter

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Chinese Journal of Integrative Medicine 2022年第7期28卷 586-593页

作者： JIANG Bing WU Ruo-ming LI Hai-dong LI Kun LI Hui DANG Wen-zhen FENG Gui-ze BAO Wei-lian YE Guan SHEN Xiao-yan Department of Pharmacology School of PharmacyFudan UniversityShanghai 200120China Department of Pharmacology of Chinese Materia Medica School of Traditional Chinese MedicineGuangdong Pharmaceutical UniversityGuangzhou 510006China Central Research Institute Shanghai Pharmaceuticals Holding Co.Ltd.Shanghai 200120China

Objective: To investigate the therapeutic effect of Yixin Ningshen Tablet(YXNS) on comorbidity of myocardial infarction(MI) and depression in rats and explore the underlying mechanism. Methods: The Sprague-Dawley rats were randomly divided into 5 groups with 7 rats in each group according to their weights,including control, model, fluoxetine(FLXT, 10 mg/kg), low-dose YXNS(LYXNS, 100 mg/kg), and high-dose YXNS(HYXNS, 300 mg/kg) groups. All rats were pretreated with corresponding drugs for 12 weeks. The rat model of MI and depression was constructed by ligation of left anterior descending coronary artery and chronic mild stress stimulation. The echocardiography, sucrose preference test, open field test, and forced swim test were performed. Myocardial infarction(MI) area and myocardial apoptosis was also detected. Serum levels of interleukin(IL)-6, IL-1β, tumor necrosis factor-α(TNF-α), 5-hydroxytryptamine(5-HT), adrenocorticotrophic hormone(ACTH), corticosterone(CORT), and norepinephrine(NE) were determined by enzyme linked immunosorbent assay. The proteins of adenosine 5’-monophosphate-activated protein kinase(AMPK), p-AMPK,peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and nuclear respiratory factor 1(NRF1) in heart were detected by Western blot analysis. The expression levels of TNF-α, IL-6, indoleamine 2,3-dioxygenase(IDO1), kynurenine 3-monooxygenase(KMO), and kynureninase(KYNU) in hippocampus were detected by real-time quantitative polymerase chain reaction. Results: Compared with the model group,the cardiac function of rats treated with YXNS significantly improved(P<0.01). Meanwhile, YXNS effectively reduced MI size and cardiomyocytes apoptosis of rats(P<0.01 or P<0.05), promoted AMPK phosphorylation,and increased PGC-1α protein expression(P<0.01 or P<0.05). HYXNS significantly increased locomotor activity of rats, decreased the levels of TNF-α, IL-6 and IL-1β, and increased the serum levels of 5-HT, NE, ACTH,and CORT(all P<0.05). More

关键词： Yixin Ningshen Tablet depression cardiovascular disorders inflammatory factor monoamine neurotransmitter kynurenine pathway Chinese medicine