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Differential metabolite analysis of the pharmacodynamic differences between different ratios of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae) herb pair

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Journal of traditional chinese medicine 2024年第3期44卷 515-523页

作者： WANG Xiang HUANG Jianping WANG Yupeng WANG Qilong JING Yajiang ZHANG Gang PENG Liang GAO Jing WANG Hongyan YAN Yonggang Department of Key Laboratory of "Qin Pharmaceutical" Research and Development Shaanxi University of Traditional Chinese Medicine Department of Yupeng shaanxi Haitian Pharmaceutical Co. Ltd. Department of Acupuncture and Tuina Shaanxi University of Traditional Chinese Medicine

OBJECTIVE: To explore the material basis of the difference of efficacy of Dahuang(Radix Et Rhizoma Rhei Palmati)-Taoren(Semen Persicae)(DT) drugs with different proportions. METHODS: Samples of different ratios of Dahuang(Radix et Rhizoma Rhei Palnati, DH) to Taoren(Semen Persicae, TR)(Group A 1∶1, B 2∶3, C 3∶2) were analyzed based on gas chromatography time-of-flight mass spectrometry untargeted metabolomics technique. RESULTS: A total of 240 primary metabolites were detected. Forty-one differential metabolites involved nine differential metabolic pathways, of which four were closely related to the efficacy of DT in the treatment of heat and blood stasis syndrome. These pathways included the biosynthesis of amino acid(phenylalanine tyrosine and tryptophan), flavonoids, unsaturated fatty acids, and the glycolysis/glycogenesis pathway. CONCLUSION: There are significant differences in the efficacy of different ratios of DT drugs, and their optimal ratio for the treatment of heat and blood stasis syndrome should be 1∶1.

关键词： Dahuang () Taoren () differential metabolites kernel drug pairs metabolic networks and pathways metabolomics

Material basis and pharmacodynamic mechanism of YangshenDingzhi granules in the intervention of viral pneumonia:Based on serum pharmacochemistry and network pharmacology

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Animal Models and Experimental medicine 2024年第3期7卷 259-274页

作者： Huirong Xu Meiyue Dong Ruikun Du Chengcheng Zhang Zinuo Chen Guangyu Tian Qinghua Cui Kejian Li College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinanChina Innovative Institute of chinese medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina Qingdao academy of chinese Medical Sciences Shandong University of Traditional Chinese MedicineQingdaoChina College of Pharmacy Shandong University of Traditional Chinese MedicineJinanChina

Background:YangshenDingzhi granules(YSDZ)are clinically effective in preventing and treating COVID-19.The present study elucidates the underlying mechanism of YSDZ intervention in viral pneumonia by employing serum pharmacochemistry and network pharmacology.Methods:The chemical constituents of YSDZ in the blood were examined using ultraperformance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Potential protein targets were obtained from the SwissTargetPrediction database,and the target genes associated with viral pneumonia were identified using GeneCards,DisGeNET,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection of blood component-related targets and disease-related targets was determined using Venny 2.1.Protein-protein interaction networks were constructed using the STRING database.The Metascape database was employed to perform enrichment analyses of Gene Ontology(GO)functions and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways for the targets,while the Cytoscape 3.9.1 software was utilized to construct drug-component-disease-target-pathway networks.Further,in vitro and in vivo experiments were performed to establish the therapeutic effectiveness of YSDZ against viral pneumonia.Results:Fifteen compounds and 124 targets linked to viral pneumonia were detected in serum.Among these,MAPK1,MAPK3,AKT1,EGFR,and TNF play significant roles.In vitro tests revealed that the medicated serum suppressed the replication of H1N1,RSV,and SARS-CoV-2 replicon.Further,in vivo testing analysis shows that YSDZ decreases the viral load in the lungs of mice infected with RSV and H1N1.Conclusion:The chemical constituents of YSDZ in the blood may elicit therapeutic effects against viral pneumonia by targeting multiple proteins and pathways.

关键词： network pharmacology pharmacodynamical material basis serum pharmacochemistry viral pneumonia YangshenDingzhi granules

Molecular Mechanism of Polysaccharides Extracted from chinese medicine Targeting Gut Microbiota for Promoting Health

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chinese Journal of Integrative medicine 2024年第2期30卷 171-180页

作者： ZHAO Wen-xiao WANG Tong ZHANG Ya-nan CHEN Qian WANG Yuan XING Yan-qing ZHENG Jun DUAN Chen-chen CHEN Lijun ZHAO Hai-jun WANG Shijun School of Nursing Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineJi'nan(250355)China Shandong Co-innovation Center of Classic traditional chinese medicine Formula Shandong University of Traditional Chinese MedicineJi'nan(250355)China College of traditional chinese medicine Shandong University of Traditional Chinese MedicineJinan(250355)China

The accumulating evidence revealed that gut microbiota plays an important role in pathological process of disease including obesity,type 2 diabetes mellitus,heart failure,and non-alcoholic fatty liver disease.Polysaccharides extracted from chinese medicine(CM)can not only alleviate pathological status but also promote health by anti-inflammatory,regulating immunity,lowering blood glucose and lipids,anti-cancer,and anti-oxidation.The alterations of gut microbiota composition and metabolism pathways are the potential mechanisms of CM polysaccharides treatment.In addition,they exert functions through gut-organ axis or play an indirect role by synergistic actions with other drugs or components mediated by gut microbiota.This review summarizes the molecular mechanisms of CM polysaccharides interacted with intestinal microbial inhabitants as potential prebiotics forpromoting health.

关键词： chinese medicine polysaccharides gut microbiota short-chain fatty acids lipopolysaccharides gut-organaxis synergistic actions

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

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chinese Journal of Integrative medicine 2024年第3期30卷 222-229页

作者： ZHANG Shuo LI Hong-jin YANG Chun-mei LIU Liu SUN Xiao-ying WANG Jiao CHEN Si-ting LU Yi HU Man-qi YAN Ge ZHOU Ya-qiong MIAO Xiao LI Xin LI Bin Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China Institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai201203China Department of Integrated traditional chinese and Western medicine Shanghai Skin Disease HospitalTongji University School of MedicineShanghai200443China

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.Methods:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number table.Histopathological changes in vivo were assessed by hematoxylin and eosin staining.Ratios of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow cytometry.Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.Results:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P<0.01).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23,tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P<0.01 or P<0.05).Furthermore,it reduced the number of γδ T17 cells in skin lesion of mice and draining lymph nodes(P<0.01).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine expression.It inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

关键词： psoriasis Tripterygium wilfordii multiglycoside γδT cells inflammation chinese medicine

Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern chinese medicine Resources Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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 Chinese Medicine

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

Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

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chinese Journal of Natural medicines 2024年第1期22卷 62-74页

作者： GUO Qiru LI Jiali WANG Zheng WU Xiao JIN Zhong ZHU Song LI Hongfei ZHANG Delai HU Wangming XU Huan YANG Lan SHI Liangqin WANG Yong College of Basic medicine Chengdu University of Traditional Chinese MedicineChengdu 610000China Chengdu University of traditional chinese medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610000China

Pathological vascular remodeling is a hallmark of various vascular diseases.Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular remodeling.Potassium dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections.This study investigates the potential of PDA in regulating pathological vascular remodeling.The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice.Experimental approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions.The results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima formation.PDA treatment significantly increased the proliferation and migration of SMCs.Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular remodeling.Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

关键词： Potassium dehydroandrographolide succinate Smooth muscle cell Myeloid differentiation factor 88 T-cadherin Pathological vascular remodeling

Effectiveness and safety of acupuncture in treatment of pregnancyrelated symptoms:a systematic review and Meta-analysis

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Journal of traditional chinese medicine 2024年第1期44卷 16-26页

作者： LIU Tingting LIU Tongou LIU Mingfu School of traditional chinese medicine Clinical medicine Hubei University of Traditional Chinese MedicineWuhan 430000China First Clinical College of Hubei University of traditional chinese medicine Wuhan 430000China Department of Acupuncture and Tuina Affiliated Hospital of Hubei University of Traditional Chinese MedicineHubei Provincial Hospital of Traditional Chinese MedicineWuhan 430000China

OBJECTIVE:To systematically evaluate the efficacy and safety of acupuncture(AM)in the treatment of pregnancyrelated symptoms such as acute vomiting during pregnancy.METHODS:We comprehensively searched the available literature up to November 2021,including Pub Med,Embase,Cochrane Library,chinese Biomedical Literature Database,and China National Knowledge Infrastructure Database,for randomized controlled trials(RCTs)on AM for the treatment of severe vomiting,insomnia,pharyngeal and pelvic pain,mood abnormalities,and dyspepsia during pregnancy.RESULTS:Sixteen RCTs with a cumulative sample size of 1178 cases were included.Of these,964 patients were included in the Meta-analysis.The Meta-analysis results showed that AM was more efficient than Western medicine in treating discomfort during pregnancy[odds ratio(OR)=1.19,95%confidence interval(CI)(1.11,1.28),P<0.01].AM was better than the control group in improving the visual analog scale scores[standard mean difference(SMD)=0.62,95%CI(0.53,0.71),P<0.01].AM was superior to the control group in improving Numerical Rating Scale(NRS)symptom scores[OR=7.31,95%CI(3.36,15.94),P<0.01].There was no significant difference in adverse effects between the AM and sham-AM groups and the analgesic drug group[OR=0.70,95%CI(0.39,1.28),P=0.25],but the treatment and control groups had mild adverse effects with a low incidence.CONCLUSIONS:AM is more effective than other treatments or pharmacotherapy alone in the treatment of pregnancy-related symptoms,and is relatively safe.However,the quality of the included trials was rather poor,and high-quality studies are required to confirm our findings.

关键词： acupuncture pregnancy nausea vomiting sleep initiation and maintenance disorders low back pain pelvic pain mood abnormalities Meta-analysis systematic review

Efficacyand Safetyof Huashi Baidu Granules in Treating Patients with SARS-CoV-2Omicron Variant: A Single-Center Retrospective Cohort Study

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chinese Journal of Integrative medicine 2024年第2期30卷 107-114页

作者： CHEN Cai-yu ZHANG Wen XU Xiang-ru PU Yu-ting TU Ya-dan PENG Wei YAO Xuan ZHOU Shuang FANG Bang-jiang Department of Emergency Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai(200032)China Department of Classical traditional chinese medicine Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Acupuncture and Massage College Shanghai University of Traditional Chinese MedicineShanghai(201203)China Institute of Emergency and Critical Care medicine Shanghai University of Traditional Chinese MedicineShanghai(200032)China

Objective:To evaluate the efficacy and safety of Huashi Baidu Granules(HSBD)in treating patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron variant.Methods:A single-center retrospective cohort study was conducted during COVID-19 Omicron epidemic in the Mobile Cabin Hospital of Shanghai New International Expo Center from April 1st to May 23rd,2022.All COVID-19 patients with asymptomatic or mild infection were assigned to the treatment group(HSBD users)and the control group(non-HSBD users).After propensity score matching in a 1:1 ratio,496 HSBD users of treatment group were matched by propensity score to 496 non-HSBD users.Patients in the treatment group were administrated HSBD(5 g/bag)orally for 1 bag twice a day for 7 consecutive days.Patients in the control group received standard care and routine treatment.The primary outcomes were the negative conversion time of nucleic acid and negative conversion rate at day 7.Secondary outcomes included the hospitalized days,the time of the first nucleic acid negative conversion,and new-onset symptoms in asymptomatic patients.Adverse events(AEs)that occurred during the study were recorded.Further subgroup analysis was conducted in vaccinated(378 HSBD users and 390 non-HSBD users)and unvaccinated patients(118 HSBD users and 106 non-HSBD users).Results:The median negative conversion time of nucleic acid in the treatment group was significantly shortened than the control group[3 days(IQR:2-5 days)vs.5 days(IQR:4-6 days);P<0.01].The negative conversion rate of nucleic acid in the treatment group were significantly higher than those in the control group at day 7(91.73%vs.86.90%,P=0.014).Compared with the control group,the hospitalized days in the treatment group were significantly reduced[10 days(IQR:8-11 days)vs.11 days(IQR:10.25-12 days);P<0.01].The time of the first nucleic acid negative conversion had significant differences between the treatment and control groups[3 days(IQR:2-4 days)vs.5 days(IQR:4-6 days);P<0.01].The incidence of new-onset sym

关键词： Huashi Baidu Granule severe acute respiratory syndrome coronavirus 2 Omicron variant retrospective cohort trial chinese medicine