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Zhuifeng tougu capsules (追风透骨胶囊) improve rheumatoid arthritis symptoms in rats by regulating the toll-like receptor 2/4-nuclear factor kappa-B signaling pathway

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Journal of Traditional chinese medicine 2021年第3期41卷 447-454页

作者： GONG Hui KUANG Gaoyan WU Yongrong LU Fangguo DENG Yihui HE Yanlin WANG Hengxin Department of oncology Hunan university of Chinese medicine integrated Chinese and Western Affiliated HospitalChangsha 410007China Department of orthopedics the First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410007China postdoctoral research station Hunan University of Chinese MedicineChangsha 410208China postdoctoral research Worksta-tion Hinye Pharmaceutical Co.Ltd.Hinye Pharmaceutical Co.Ltd.Changsha 410331China

OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules(追风透骨胶囊, ZFTG) in the treatment of rheumatoid arthritis(RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B(TLR2/4-NF-κB) signaling pathway.METHODS: TypeⅡ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-,and low-dose ZFTG groups. The methotrexate(MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index(AI) score were measured. The production of C-reactive protein(CRP), erythrocyte sedimentation rate(ESR), and rheumatoid factors(RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by western blotting, and the m RNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction.RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased(P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident(P < 0.01).CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway.

关键词： arthritis rheumatoid wind-cold-dampness syndrome toll-like receptors NF-kappa B Zhuifeng tougu capsule

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The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1288-1304页

作者： Geni Ye Maohua Huang Yong Li Jie Ouyang Minfeng Chen Qing Wen Xiaobo Li Huhu Zeng Pei Long Zepei Fan Junqiang Yin Wencai Ye Dongmei Zhang College of Pharmacy Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional chinese medicine and New Drugs research Jinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Department of Musculoskeletal Oncology the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently,there are no molecular targeted drugs approved for osteosarcoma treatment,particularly effective drugs for osteosarcoma with pulmonary metastases.It has been reported that fibroblast activation protein alpha(FAPa)is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis,demonstrating that FAPa-targeted agents might be a promising therapeutic strategy for osteosarcoma.In the present study,we reported that the FAPa-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPa-positive osteosarcoma cells in vitro and in vivo.Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells.Importantly,it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition(EMT)of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo.Mechanistically,Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway,leading to inhibition of the growth and metastatic spread of osteosarcoma cells.These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPa-positive osteosarcoma,particularly osteosarcoma with pulmonary metastases.

关键词： Osteosarcoma Fibroblast activation protein alpha Growth Pulmonary metastasis Vinblastine prodrug AXL β-Catenin

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Interim Analysis Report of Kuanxiong Aerosol in Improving Angina and Quality of Life after Percutaneous Coronary Intervention

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World Journal of Traditional chinese medicine 2022年第1期8卷 87-91页

作者： Luo-Qi Lin Bing-Xin Wu Miao-Yang Lin Qiu-Xiong Chen Dan-Ping Xu The Second Clinical Medical College Guangzhou University of Chinese Medicine Department of Cardiology The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou postdoctoral research station Institute of Integrative Chinese and Western MedicineFujian University of Traditional Chinese MedicineFuzhouChina

Objective: The objective is to observe the effect of Kuanxiong aerosol(KXA) on angina and the quality of life of patients after percutaneous coronary intervention(PCI). Materials and Methods: Six hundred patients with angina after PCI(AAP) were randomly assigned to an experimental group and a control group(n = 300 in each group) and received basic treatment with KXA or basic treatment(respectively) for 8 weeks. The Seattle Angina Questionnaire(SAQ) and visual analog scale(VAS) scores of the two groups during the screening period and five follow-up periods were compared. Results: A total of 179 patients were included in this interim report, including 85 in the experimental group and 94 in the control group. Among the five-dimensional scores of the SAQ, the improvement in the angina frequency and quality of life scores in the experimental group was better than those in the control group after treatment(P 0.01). The difference in VAS scores between the two groups was not statistically significant(P > 0.01). No obvious adverse reactions were observed between the two groups. Conclusions: KXA can reduce the frequency of AAP and improve patients’ quality of life.

关键词： Angina Kuanxiong aerosol percutaneous coronary intervention quality of life

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The disbalance of LRP1 and SIRPα by psychological stress dampens the clearance of tumor cells by macrophages

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Acta Pharmaceutica Sinica B 2022年第1期12卷 197-209页

作者： Yanping Wu Xiang Luo Qingqing Zhou Haibiao Gong Huaying Gao Tongzheng Liu Jiaxu Chen Lei Liang Hiroshi Kurihara Yi-Fang Li Rong-Rong He Guangdong Engineering research Center of chinese medicine&Disease Susceptibility Jinan UniversityGuangzhou 510632China International Cooperative Laboratory of Traditional chinese medicine Modernization and Innovative Drug Development of chinese Ministry of Education College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional chinese medicine and New Drugs research College of PharmacyJinan UniversityGuangzhou 510632China Formula-pattern research Center School of Traditional Chinese MedicineJinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Institute of Tumor Pharmacology College of PharmacyJinan UniversityGuangzhou 510632China

The relationship between chronic psychological stress and tumorigenesis has been well defined in epidemiological studies;however, the underlying mechanism remains underexplored. In this study, we discovered that impaired macrophage phagocytosis contributed to the psychological stressevoked tumor susceptibility, and the stress hormone glucocorticoid(GC) was identified as a principal detrimental factor. Mechanistically, GC disturbed the balance of the "eat me" signal receptor(low-density lipoprotein receptor-related protein-1, LRP1) and the "don’t eat me" signal receptor(signal regulatory protein alpha, SIRPa). Further analysis revealed that GC led to a direct, glucocorticoid receptor(GR)-dependent trans-repression of LRP1 expression, and the repressed LRP1, in turn, resulted in the elevatedgene level of SIRPa by down-regulating mi RNA-4695-3 p. These data collectively demonstrate that stress induces the imbalance of the LRP1/SIRPa axis and entails the disturbance of tumor cell clearance by macrophages. Our findings provide the mechanistic insight into psychological stress-evoked tumor susceptibility and indicate that the balance of LRP1/SIRPa axis may serve as a potential therapeutic strategy for tumor treatment.

关键词： Psychological stress Tumorigenesis Macrophages Phagocytosis LRP1 SIRPa Therapeutic target

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Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875

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chinese Journal of Natural medicines 2021年第9期19卷 700-705页

作者： ZOU Jian ZHANG Shuai ZHAO Huan WANG Yong-Heng ZHOU Zheng-Qun CHEN Guo-Dong HU Dan LI Ning YAO Xin-Sheng GAO Hao Institute of Traditional chinese medicine&Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents ofTCM and New Drugs ResearchJinan UniversityGuangzhou 510632China College of Traditional chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China College of Traditional chinese medicine Jinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China

Biotransformation ofα-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans,(+)(7 S,8 S,7’S,8’R)iso-magnosalicin(1 a)/(-)(7 R,8 R,7’R,8’S)iso-magnosalicin(1 b)and(+)(7 R,8 R,7’S,8’R)magnosalicin(2 a)/(-)(7 S,8 S,7’R,8’S)magnosalicin(2 b),and four known metabolites,(±)acoraminol A(3),(±)acoraminol B(4),asaraldehyde(5),and 2,4,5-trimethoxybenzoic acid(6).Their structures,including absolute configurations,were determined by extensive analysis of NMR spectra,X-ray crystallography,and quantum chemical ECD calculations.The cytotoxic activity and Aβ_(42)aggregation inhibitory activity of all the compounds were evaluated.Compound 2 displayed significant anti-Aβ_(42)aggregation activity with an inhibitory rate of 60.81%(the positive control EGCG:69.17%).In addition the biotransformation pathway ofα-asarone by Alternaria longipes CGMCC 3.2875 was proposed.

关键词： Biotransformation α-Asarone Alternaria longipes CGMCC 3.2875 Anti-Aβ_(42)aggregation activity

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Author correction to“The FAPα-activated prodrug Z-GP-DAVLBH inhibits the growth and pulmonary metastasis of osteosarcoma cells by suppressing the AXL pathway”[Acta Pharm Sin B 12(2022)1288–1304]

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1337-1339页

作者： Geni Ye Maohua Huang Yong Li Jie Ouyang Minfeng Chen Qing Weng Xiaobo Li Huhu Zeng Pei Long Zepei Fan Junqiang Yin Wencai Ye Dongmei Zhang College of Pharmacy Jinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional chinese medicine and New Drugs research Jinan UniversityGuangzhou 510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Department of Musculoskeletal Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

We deeply regret that the representative image of invaded 143B cells treated with Z-GP-DAVLBH + AXL-KD in the lower panel of Fig. 6C was incorrect due to inadvertent mistake of copying and pasting in the process of assembling figures with Adobe Illustrator software. The image has now been corrected, and the quantification of cell invasion in Fig. 6C remains correct. The corrected version of Fig. 6C has been provided below, and the change did not affect the results and conclusions of this study. We have provided the original data of this figure to Editorial Office, and the Editorial Office or the corresponding authors can be contacted for original data access.

关键词： Illustrator correction image

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New ent-kaurane diterpenes with chiral epoxyangelate moieties from Wedelia prostrata

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chinese Chemical Letters 2019年第2期30卷 451-453页

作者： Zhongnan Wu Yubo Zhang Wen Li Nenghua Chen Qianwen Niu Yingying Li Qingguo Li Dan Yang Yaolan Li Guocai Wang Institute of Traditional chinese medicine ξ Natural Products College of Pharmacy and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchJinan University Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan University School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine Department of Specific Diagnosis The 324th Military Hospital

Four new ent-kaurane diterpenes with chiral epoxyangelate moieties, (2′R,3′R)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (1), (2′S,3′S)-3 a- (2′,3′-epoxyangeloyloxy)-kaur-16-en-19-oic acid (2), (2′S,3′R)-3 a- (2',3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (3) and (2′R,3′S)-3α- (2′,3'-epoxyangeloyloxy)-kaur-16-en-19-oic acid (4), along with eight known diterpenes (5-12), were isolated from Wedelia prostrata. The absolute configurations of the new structures were determined by X-ray crystallography,ECD calculations and chemical methods. All compounds were evaluated for their cytotoxicity activities on human HepG-2 cells,with IC_(50) values of 11.72 ±0.22 μmol/L to 54.75±1.12 μmol/L.

关键词： Wedelia prostrata Chiral epoxyangelate moieties Ent-kaurane diterpenes Absolute configuration Cytotoxicity activities

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Ganoderma lucidum spore oil(GLSO),a novel antioxidant,extends the average life span in Drosophila melanogaster

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Food Science and Human Wellness 2021年第1期10卷 38-44页

作者： Yi Zhang Hongfei Cai Zhu Tao Cheng Yuan Zhaojian Jiang Juyan Liu Hiroshi Kurihara Wendong Xu Institute of Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China postdoctoral research station of Guangzhou Pharmaceutical Holdings Limited Guangdong 510130China Institute of National Engineering research Center for Modernization of Extraction and Separation Process of Traditional chinese medicine Hanfang Pharmaceutical Co.LtdGuangdong 510240China Guangzhou Pharmaceutical Holdings Ltd Guangdong 510130China Institute of Traditional chinese medicine and Natural Products Jinan University601Huangpu Avenue WestGuangzhou510632China

In ancient China,Ganoderma lucidum was believed to be a medical fungus that could increase lifespan.Recently,pharmacologic studies have found that polysaccharide peptides and triterpenoids extracted from Ganoderma lucidum have various physiological effects as active compounds.However,the effects of spore oil isolated from Ganoderma lucidum remains unknown.In this study,the biological effects of Ganoderma lucidum spore oil(GLSO)were evaluated using a Drosophila melanogaster model.Compared with untreated groups,groups treated with GLSO had significantly longer average and maximum lifespan in both normal conditions and under oxidative stress.The activities of various antioxidant enzymes were measured to determine the antioxidant effect of GLSO.GLSO treatment markedly enhanced total superoxide dismutase(SOD)and catalase(CAT)activity and decreased levels of malondialdehyde(MDA).Further,we found dose-dependent increases in the mRNA expression of Cu,Zn-SOD,Mn-SOD,and CAT in GLSO-treated groups.These results suggest that GLSO may effectively eliminate free radicals and extend lifespan in Drosophila.Future work should investigate the value of GLSO as a functional food for the prevention of aging in larger animal models.

关键词： Ganoderma lucidum spore oil Antioxidant activity Drosophila melanogaster Anti-aging

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Crosstalk between nano/micro particulate technologies and chinese medicine: a bibliometric analysis

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Traditional medicine research 2023年第6期8卷 9-23页

作者： Zheng-Wei Huang Meng-Qin Guo Wen-Hao Wang Jian-Bo He Chuan-Bin Wu Xin Pan Xue-Juan Zhang Ying Huang Ping Hu College of Pharmacy Jinan UniversityGuangzhou 511436China School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Guangdong Engineering research Center of chinese medicine&Disease Susceptibility Integrated Chinese and Western Medicine Postdoctoral Research StationJinan UniversityGuangzhou 510632China

Background:chinese medicine is widely applied in Asian and western countries for its outstanding therapeutic effect,but there are still unsolved problems such as unclear active ingredients and pharmacological effects.The application of nano/microparticle technology in chinese medicine may become a promising strategy to solve this problem in the near future(provided that more efforts are made to in-depth exploration).In this work,a comprehensive analysis of the field was carried out from a bibliometrics perspective,and further the publishing trends and research hotspots were figured out.Methods:The articles or reviews from 2000 to 2020 were retrieved in the database of Web of Science Core Collection.The documents were processed by Clarivate Analytic,Visualization of Similarities viewer,Statistical Analysis Toolkit for Informetrics and bibliometric online platform,and the data were visualized.Finally,a bibliometric summary,citation analysis results and research trends were described.Results:A bibliometric analysis of 773 articles of interest showed that research in this field had continued to grow in recent years,with a high degree of interdisciplinary integration.Secondly,this field attached great importance to the quantitative analysis of chinese medicine combined with nano/micro particle technology.chinese medicine,nanoparticles and liposomes were the most accessed keywords.China was the main contributing country,and the top-10 contributing organizations were all located in China.Co-authorship was a common phenomenon in this field.Conclusion:The published literature on the application of nano/micro particle technology in chinese medicine was summarized.The results suggested that bibliometric analysis could predict possible directions for future research in this field.

关键词： chinese medicine nanotechnology bibliometric analysis Web of Science

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Electrochemical detection of methyl-paraoxon based on bifunctional cerium oxide nanozyme with catalytic activity and signal amplification effect

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Journal of Pharmaceutical Analysis 2021年第5期11卷 653-660页

作者： Yuzhou Sun Jinchao Wei Jian Zou Zehua Cheng Zhongming Huang Liqiang Gu Zhangfeng Zhong Shengliang Li Yitao Wang Peng Li State Key Laboratory of Quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Institute of Traditional chinese medicine&Natural Products College of PharmacyJinan UniversityGuangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchGuangzhou510632China Integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou510632China Center of Super-Diamond and Advanced Films(COSDAF)and Department of Chemistry City University of Hong KongHong Kong999077China

A new electrochemical sensor for organophosphate pesticide(methyl-paraoxon)detection based on bifunctional cerium oxide(CeO_(2))nanozyme is here reported for the first time.Methyl-paraoxon was degraded into p-nitrophenol by using CeO_(2) with phosphatase mimicking activity.The CeO_(2) nanozymemodified electrode was then synthesized to detect p-nitrophenol.Cyclic voltammetry was applied to investigate the electrochemical behavior of the modified electrode,which indicates that the signal enhancement effect may attribute to the coating of CeO_(2) nanozyme.The current research also studied and discussed the main parameters affecting the analytical signal,including accumulation potential,accumulation time,and pH.Under the optimum conditions,the present method provided a wider linear range from 0.1 to 100 mmol/L for methyl-paraoxon with a detection limit of 0.06 mmol/L.To validate the proof of concept,the electrochemical sensor was then successfully applied for the determination of methyl-paraoxon in three herb samples,i.e.,Coix lacryma-jobi,Adenophora stricta and Semen nelumbinis.Our findings may provide new insights into the application of bifunctional nanozyme in electrochemical detection of organophosphorus pesticide.

关键词： chinese medicine Nanozyme Organophosphorus Pesticide Methyl-paraoxon Electroanalysis

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