1.Establishment of different pneumonia mouse models suitable for traditional Chinese medicine screening.
Xing-Nan YUE ; Jia-Yin HAN ; Chen PAN ; Yu-Shi ZHANG ; Su-Yan LIU ; Yong ZHAO ; Xiao-Meng ZHANG ; Jing-Wen WU ; Xuan TANG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(15):4089-4099
In this study, lipopolysaccharide(LPS), ovalbumin(OVA), and compound 48/80(C48/80) were administered to establish non-infectious pneumonia models under simulated clinical conditions, and the correlation between their pathological characteristics and traditional Chinese medicine(TCM) syndromes was compared, providing the basis for the selection of appropriate animal models for TCM efficacy evaluation. An acute pneumonia model was established by nasal instillation of LPS combined with intraperitoneal injection for intensive stimulation. Three doses of OVA mixed with aluminum hydroxide adjuvant were injected intraperitoneally on days one, three, and five and OVA was administered via endotracheal drip for excitation on days 14-18 to establish an OVA-induced allergic pneumonia model. A single intravenous injection of three doses of C48/80 was adopted to establish a C48/80-induced pneumonia model. By detecting the changes in peripheral blood leukocyte classification, lung tissue and plasma cytokines, immunoglobulins(Ig), histamine levels, and arachidonic acid metabolites, the multi-dimensional analysis was carried out based on pathological evaluation. The results showed that the three models could cause pulmonary edema, increased wet weight in the lung, and obvious exudative inflammation in lung tissue pathology, especially for LPS. A number of pyrogenic cytokines, inclading interleukin(IL)-6, interferon(IFN)-γ, IL-1β, and IL-4 were significantly elevated in the LPS pneumonia model. Significantly increased levels of prostacyclin analogs such as prostaglandin E2(PGE2) and PGD2, which cause increased vascular permeability, and neutrophils in peripheral blood were significantly elevated. The model could partly reflect the clinical characteristics of phlegm heat accumulating in the lung or dampness toxin obstructing the lung. The OVA model showed that the sensitization mediators IgE and leukotriene E4(LTE4) were increased, and the anti-inflammatory prostacyclin 6-keto-PGF2α was decreased. Immune cells(lymphocytes and monocytes) were decreased, and inflammatory cells(neutrophils and basophils) were increased, reflecting the characteristics of "deficiency", "phlegm", or "dampness". Lymphocytes, monocytes, and basophils were significantly increased in the C48/80 model. The phenotype of the model was that the content of histamine, a large number of prostacyclins(6-keto-PGE1, PGF2α, 15-keto-PGF2α, 6-keto-PGF1α, 13,14-D-15-keto-PGE2, PGD2, PGE2, and PGH2), LTE4, and 5-hydroxyeicosatetraenoic acid(5S-HETE) was significantly increased, and these indicators were associated with vascular expansion and increased vascular permeability. The pyrogenic inflammatory cytokines were not increased. The C48/80 model reflected the characteristics of cold and damp accumulation. In the study, three non-infectious pneumonia models were constructed. The LPS model exhibited neutrophil infiltration and elevated inflammatory factors, which was suitable for the efficacy study of TCM for clearing heat, detoxifying, removing dampness, and eliminating phlegm. The OVA model, which took allergic inflammation as an index, was suitable for the efficacy study of Yiqi Gubiao formulas. The C48/80 model exhibited increased vasoactive substances(histamine, PGs, and LTE4), which was suitable for the efficacy study and evaluation of TCM for warming the lung, dispersing cold, drying dampness, and resolving phlegm. The study provides a theoretical basis for model selection for the efficacy evaluation of TCM in the treatment of pneumonia.
Animals
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Disease Models, Animal
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Mice
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Pneumonia/genetics*
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Medicine, Chinese Traditional
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Male
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Humans
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Cytokines/immunology*
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Female
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Lipopolysaccharides/adverse effects*
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Lung/drug effects*
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Drugs, Chinese Herbal
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Ovalbumin
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Mice, Inbred BALB C
2.Anti-fibrosis Action of Therapy of Tonifying Kidney and Removing Stasis on Moderate-to-Severe Intrauterine Adhesions and Its Influence on Extracellular Matrix Degradation Related Factors in Menstrual Blood
Ping-Ting XING ; Ai-Li WANG ; Yan-Xin CHEN
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(1):96-104
Objective To investigate the anti-fibrosis action of the therapy of tonifying kidney and removing stasis(shortened to Bushen Quyu method)on moderate-to-severe intrauterine adhesion and its influence on extracellular matrix degradation related factors in menstrual blood.Methods A total of 124 patients with moderate-to-severe intrauterine adhesions of kidney deficiency and blood stasis syndrome who were to undergo transcervical resection of adhesion(TCRA)were randomly divided into a study group and a control group,with 62 patients in each group.Both groups were given TCRA treatment.After the operation,the control group was treated with Progesterone + Estradiol Valerate Tablets,and the study group was treated with the combination of the Bushen Quyu method by using modified Guishen Decoction based on the treatment of the control group.The treatment covered 3 menstrual cycles.The changes in menstrual status,transvaginal color Doppler sonography parameters,scores of kidney deficiency and blood stasis syndrome,and scores of uterine adhesion in the two groups were observed before and after the treatment.Moreover,the two groups were observed before and after treatment in the changes of vascular endothelial growth factor(VEGF),transforming growth factor β1(TGF-β1),platelet-derived growth factor(PDGF),and connective tissue growth factor(CTGF)as well as the mRNA expression levels of matrix metalloproteinase 9(MMP-9),matrix metalloproteinase inhibitory factor 1(TIMP-1),phosphatidylinositol-3-hydroxykinase(PI3K)and collagen type I A1 protein(COL1A1).After treatment,the clinical efficacy and safety of the two groups were assessed.Results(1)After 3 menstrual cycles of treatment,the total effective rate in the study group was 93.55%(58/62),and that in the control group was 80.65%(50/62).The intergroup comparison showed that the therapeutic effect of the study group was significantly superior to that of the control group(P<0.05).(2)After treatment,the menstrual flow,menstrual cycle and menstrual period of the two groups were significantly improved compared with those before treatment(P<0.05),and the recovery of menstrual flow,menstrual cycle and menstrual period in the study group was significantly superior to that in the control group after treatment(P<0.05).(3)After treatment,the transvaginal color Doppler sonography parameters of uterine blood flow index(FI),pulsatility index(PI),resistance index(RI),uterine cavity volume,and endometrial thickness in the two groups were significantly improved compared with those before treatment(P<0.05).And the study group had significantly higher FI,uterine cavity volume,and endometrial thickness and had lower PI and RI than the control group(P<0.05 or P<0.01).(4)After treatment,the scores of uterine adhesion and the scores of kidney deficiency and blood stasis syndrome in the two groups were significantly decreased compared with those before treatment(P<0.05),and the above scores in the study group were significantly lower than those of the control group after treatment(P<0.01).(5)After treatment,the levels of VEGF,TGF-β1,PDGF,and CTGF in the two groups were significantly decreased compared with those before treatment(P<0.05),and the levels of the above cytokines in the study group were significantly lower than those in the control group after treatment(P<0.01).(6)After treatment,the relative mRNA expression levels of MMP-9 and PI3K in the menstrual blood of the two groups were significantly higher and the mRNA expression level of COL1A1 was significantly lower than that before treatment(P<0.05).And the study group had higher mRNA expression levels of MMP-9 and PI3K in the menstrual blood than the control group after treatment(P<0.05 or P<0.01).(7)The total incidence of adverse reactions in the control group was 25.81%(16/62)and that in the study group was 16.13%(10/62).The intergroup comparison showed that the difference between the two groups was not statistically significant(P>0.05).The symptoms of adverse reactions in the two groups disappeared after symptomatic treatment,and there were no adverse reactions related to the medication of Chinese medicine during the study.Conclusion The combination of Bushen Quyu formula combined with western medicine is more effective than western medicine alone for the treatment of patients with uterine adhesions after TCRA.The application of Bushen Quyu formula can further promote the recovery of menstruation in the patients,improve the circulation of blood flow in the endometrium,increase the endometrial thickness,regulate the expression of fibrosis factors,up-regulate the mRNA expressions of PI3K and MMP-9,restore the balance of the extracellular matrix(ECM),and prevent the reoccurrence of intrauterine adhesions.And its clinical medication is safe.
3.Expert consensus on ethical requirements for artificial intelligence (AI) processing medical data.
Cong LI ; Xiao-Yan ZHANG ; Yun-Hong WU ; Xiao-Lei YANG ; Hua-Rong YU ; Hong-Bo JIN ; Ying-Bo LI ; Zhao-Hui ZHU ; Rui LIU ; Na LIU ; Yi XIE ; Lin-Li LYU ; Xin-Hong ZHU ; Hong TANG ; Hong-Fang LI ; Hong-Li LI ; Xiang-Jun ZENG ; Zai-Xing CHEN ; Xiao-Fang FAN ; Yan WANG ; Zhi-Juan WU ; Zun-Qiu WU ; Ya-Qun GUAN ; Ming-Ming XUE ; Bin LUO ; Ai-Mei WANG ; Xin-Wang YANG ; Ying YING ; Xiu-Hong YANG ; Xin-Zhong HUANG ; Ming-Fei LANG ; Shi-Min CHEN ; Huan-Huan ZHANG ; Zhong ZHANG ; Wu HUANG ; Guo-Biao XU ; Jia-Qi LIU ; Tao SONG ; Jing XIAO ; Yun-Long XIA ; You-Fei GUAN ; Liang ZHU
Acta Physiologica Sinica 2024;76(6):937-942
As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence*
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Humans
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Consensus
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Computer Security/standards*
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Confidentiality/ethics*
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Informed Consent/ethics*
4.miR-193a-5p Inhibits Macrophage Lipid Accumulation via the HDAC9-ABCA1/G1 Pathway
Yan WANG ; Zhi-Yong SONG ; Wei-Min AI ; Jin-Xing CAI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(12):1751-1760
Previous studies have shown that microRNA-193a-5p (miR-193a-5p) was related to fatty acid metabolism in epithelial cells,whereas its role in macrophage lipid accumulation is unclear.Histone deacetylase 9 (HDAC9) could deacetylate ATP-binding cassette transporter A1/G1 (ABCA1/G1) and decrease their expression,inhibiting macrophage cholesterol efflux and promoting foam cell formation.This study explores the effects of miR-193a-5p on lipid accumulation in THP-1 macrophages and its rela-tionship with HDAC9.RT-PCR showed that miR-193a-5p levels were significantly decreased in THP-1-derived foam cells.RT-PCR and Western blotting results suggested that miR-193a-5p overexpression sig-nificantly up-regulated the mRNA and protein levels of ABCA1 and ABCG1,while it did not affect the expression of SR-A,SR-BI or CD36.Oil Red O staining and liquid scintillation counting indicated that miR-193a-5p mimic transfection markedly promoted cholesterol efflux and decreased lipid droplet num-bers without altering the uptake of DiL-ox-LDL.High-performance liquid chromatography (HPLC) assay showed that miR-193a-5p overexpression decreased intracellular contents of total cholesterol (TC),cho-lesterol ester (CE),and free cholesterol (FC) in THP-1-derived foam cells.These inhibitory effects of miR-193a-5p on foam cell formation became more evident after HDAC9 siRNA treatment and were mainly reversed by HDAC9 overexpression (P<0.05) .Furthermore,luciferase reporter assay and Western blot-ting showed that miR-193a-5p directly targeted HDAC93'UTR,thereby down-regulating its protein ex-pression (P<0.05) .Altogether,miR-193a-5p inhibits lipid accumulation in THP-1 macrophages via the HDAC9-ABCA1/G1 pathway.
5.miR-193a-5p Inhibits Macrophage Lipid Accumulation via the HDAC9-ABCA1/G1 Pathway
Yan WANG ; Zhi-Yong SONG ; Wei-Min AI ; Jin-Xing CAI
Chinese Journal of Biochemistry and Molecular Biology 2024;40(12):1751-1760
Previous studies have shown that microRNA-193a-5p (miR-193a-5p) was related to fatty acid metabolism in epithelial cells,whereas its role in macrophage lipid accumulation is unclear.Histone deacetylase 9 (HDAC9) could deacetylate ATP-binding cassette transporter A1/G1 (ABCA1/G1) and decrease their expression,inhibiting macrophage cholesterol efflux and promoting foam cell formation.This study explores the effects of miR-193a-5p on lipid accumulation in THP-1 macrophages and its rela-tionship with HDAC9.RT-PCR showed that miR-193a-5p levels were significantly decreased in THP-1-derived foam cells.RT-PCR and Western blotting results suggested that miR-193a-5p overexpression sig-nificantly up-regulated the mRNA and protein levels of ABCA1 and ABCG1,while it did not affect the expression of SR-A,SR-BI or CD36.Oil Red O staining and liquid scintillation counting indicated that miR-193a-5p mimic transfection markedly promoted cholesterol efflux and decreased lipid droplet num-bers without altering the uptake of DiL-ox-LDL.High-performance liquid chromatography (HPLC) assay showed that miR-193a-5p overexpression decreased intracellular contents of total cholesterol (TC),cho-lesterol ester (CE),and free cholesterol (FC) in THP-1-derived foam cells.These inhibitory effects of miR-193a-5p on foam cell formation became more evident after HDAC9 siRNA treatment and were mainly reversed by HDAC9 overexpression (P<0.05) .Furthermore,luciferase reporter assay and Western blot-ting showed that miR-193a-5p directly targeted HDAC93'UTR,thereby down-regulating its protein ex-pression (P<0.05) .Altogether,miR-193a-5p inhibits lipid accumulation in THP-1 macrophages via the HDAC9-ABCA1/G1 pathway.
6.Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version).
Wei-An YUAN ; Jun-Hua ZHANG ; Jian-Ping LIU ; Zhong-Qi YANG ; Jun-Ling CAO ; Xing LIAO ; Xiao-Yu XI ; Mei HAN ; Wen-Yuan LI ; Zhen-Wen QIU ; Shi-Yin FENG ; Yuan-Yuan GUO ; Lu-Jia CAO ; Xiao-Hong LIAO ; Yan-Ling AI ; Ju HUANG ; Lu-Lu JIA ; Xiang-Fei SU ; Xue WU ; Ze-Qi DAI ; Ji-Hua GUO ; Bing-Qing LU ; Xiao-Xiao ZHANG ; Jian-Yuan TANG
China Journal of Chinese Materia Medica 2023;48(1):256-264
Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional
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Nonprescription Drugs
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Consensus
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China
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Reference Standards
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Drugs, Chinese Herbal
7.miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer
Bin WANG ; Kun WANG ; Jian YU ; Xiao-meng HAO ; Yu-lu LIU ; Ai-Yan XING
Journal of Breast Cancer 2022;25(3):193-206
Purpose:
Neoadjuvant chemotherapy (NAC) is widely used to treat breast cancer (BC). The prediction and evaluation of chemotherapy responses remains a significant challenge.
Methods:
MicroRNAs (miRNAs) play a crucial role in cancer drug resistance. We used a miRNA microarray and identified that miR-638 is downregulated in chemoresistant cases.However, the exact role of miR-638 and the underlying mechanisms of chemoresistance remain unclear. Using real-time quantitative reverse transcription polymerase chain reaction, we found significant downregulation of miR-638 in chemoresistant patients compared with chemosensitive patients. To explore the function of miR-638, we overexpressed and inhibited miR-638 expression in MDA-MB-231 and MCF-7 cells by transfecting them with miR-638 mimics and miR-638 inhibitor, respectively. Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. A minimal patient-derived xenograft (MiniPDX™) model was established to evaluate the chemosensitivity to different drugs.
Results:
The results showed that cell proliferation decreased and cell apoptosis increased in cells transfected with the miR-638 mimic, and cell proliferation and apoptosis were reversed with transfection of miR-638 inhibitor compared with the control group. Among patients who received 5-fluorouracil (5-FU), miR-638 expression levels were lower in the chemoresistant group than in the chemosensitive group. The MiniPDX™ model showed that MDA-MB-231 cells overexpressing miR-638 were more susceptible to 5-FU treatment in vivo.
Conclusion
We provided evidence of acquired resistance to 5-FU caused by miR-638 deficiency. Alterations in miR-638 may be used with 5-FU chemotherapy during NAC for BC.
8.Minimal clinically important difference of the frequency of bowel movement for patients with chronic severe functional constipation treated with acupuncture.
Yan-Ke AI ; Zhi-Shun LIU ; Bao-Yan LIU ; Yan-Hong ZHANG ; Yang LI ; Hai-Shu SUN ; Xue CAO ; Jia LIU ; Zhuo-Xin YANG ; Hai-Bo YU ; Xing-Xian HUANG ; Li-Yun HE
Chinese Acupuncture & Moxibustion 2022;42(11):1247-1250
OBJECTIVE:
To estimate the minimal clinically important difference (MCID) of the frequency of bowel movement for the patients with chronic severe functional constipation treated with acupuncture so as to provide the evidence for the clinical decision.
METHODS:
In this study, 813 patients with chronic severe functional constipation treated with acupuncture in two previous randomized controlled trials were included. Through the anchor-based method (anchored by the item 28 "satisfaction with previous treatment" of the patient assessment of constipation-quality of life [PAC-QOL]) and the distribution-based method, the MCID of the weekly frequency of complete spontaneous bowel movement (CSBM) and spontaneous bowel movement (SBM) was analyzed statistically in the patients.
RESULTS:
The MCID of the mean weekly frequency of CSBM and SBM was 1.3 times and 1.6 times in patients with chronic severe functional constipation treated with acupuncture, respectively.
CONCLUSION
The mean increase of the weekly CSMB is ≥ 1.3 times and that of SBM is ≥ 1.6 times after treatment when compared with the baseline respectively, suggesting the clinical significance.
Humans
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Quality of Life
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Minimal Clinically Important Difference
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Treatment Outcome
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Constipation/therapy*
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Acupuncture Therapy
9.Comparison between macroscopic identification and DNA barcoding identification of Amomi Fructus.
En-Ai ZHAI ; Wen-Juan MI ; Yang CUI ; Wei-Feng HONG ; Ya-Shun WANG ; Xing-Yu GUO ; Hui-Qin ZOU ; Yong-Hong YAN
China Journal of Chinese Materia Medica 2022;47(17):4600-4608
This study aims to explore the consistency between macroscopic identification and DNA barcoding identification of Amomi Fructus. With the DNA barcoding identification results, we evaluated the reliability of identifying Amomi Fructus quality by combining macroscopic traits with main volatile chemical components. Thirteen batches of Amomi Fructus samples were collected for identification. Firstly, the morphological and sensory characteristics of each sample were observed and recorded according to the standard in Chinese Pharmacopoeia(2020 edition). The 100-fruit weight, longitudinal diameter, transverse diameter, and longitudinal diameter-to-transverse diameter ratio were measured, which correspond to large, solid, and full kernel representing good quality in the sensory evaluation. The odor value detected by electronic nose and major volatile components(borneol, camphor, limonene, and borneol acetate) correspond to the sensory evaluation of strong odor representing good quality. Secondly, DNA barcoding was employed to identify the 13 batches of samples. Finally, clustering analysis was performed for the main volatile components and macroscopic traits, and the identification results were compared with those of DNA barcoding. Except two batches of samples(No.6 and No.10), the macroscopic identification showed the results consistent with those of DNA barcoding, with an identification rate of 84.62%. The clustering results of the content of four volatile chemical components and macroscopic traits were also consistent with the DNA barcoding identification results. DNA barcoding can verify the results of macroscopic identification and provide a scientific basis for the inheritance and development of macroscopic identification. Moreover, the combination of macroscopic traits and chemical components demonstrates higher accuracy in the quality evaluation of Chinese medicinal materials.
Camphanes
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Camphor/analysis*
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DNA Barcoding, Taxonomic
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Drugs, Chinese Herbal/chemistry*
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Fruit/genetics*
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Limonene/analysis*
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Reproducibility of Results
10.Molecular Mechanism of Nardostachyos Radix et Rhizoma-Agrimoniae Herba in Treatment of Arrhythmia Based on Network Pharmacology
Yu-zhen AI ; Xiao-juan MA ; Ya-xuan XING ; Long-mei YAN ; An-ran GAO ; Qi-wu XU ; Zhi-jie XU ; Xian-yu WU ; Hui-rong GAO ; Jing-chun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(3):204-211
ObjectiveTo explore the material basis and mechanism of Nardostachyos Radix et Rhizoma (NRER)-Agrimoniae Herba (AH), the herbal pair effective in regulating the liver, invigorating Qi, and calming palpitations, in the treatment of premature ventricular contractions (PVCs) by network pharmacology and molecular docking. MethodThe chemical components and targets of NRER and AH were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) combined with relevant literature. GeneCards,Online Mendelian Inheritance in Man(OMIM),and DrugBank were used to predict the potential targets against PVCs. STRING platform was used for protein-protein interaction (PPI) analysis. Metascape platform was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Cytoscape 3.8.0 was used to construct the NRER-AH component-potential target-signaling pathway network. The main target proteins underwent molecular docking to the active components of NRER-AH by AutoDock 4.2.6. ResultThe targets of nine active components in NRER-AH (such as quercetin,kaempferol,and acacetin) against PVCs mainly involved tumor necrosis factor (TNF),mitogen-activated protein kinase 1(MAPK1),and protein kinase B1(Akt1). The potential targets were mainly enriched in 26 signaling pathways,such as pathways in cancer and the advanced glycosylation end product (AGE)-receptor of advanced glycosylation end product(RAGE) signaling pathway. The results of molecular docking showed that the majority of the active components (92.59%) of NRER-AH had good binding activities with the main target proteins TNF,MAPK1,and Akt1. ConclusionThe active components of NRER-AH can regulate cardiac ion channels,resist inflammation, and combat oxidative stress to treat PVCs through multi-target and multi-pathway interventions. They can also improve symptoms related to depression and anxiety by inhibiting monoamine oxidase activity and protecting nerves from damage. This study is expected to provide research ideas and the theoretical basis for further exploring the material basis and mechanism of NRER-AH in the treatment of PVCs.

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