NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2024, Vol. 36 ›› Issue (5): 868-880.doi: 10.16333/j.1001-6880.2024.5.016

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Intervention mechanism of Jianpi Chutan Jiedu Decoction on lung cancer based on integrated pharmacology and experimental validation

ZHAN Xue1,FENG Shi-han1,YANG Qi1,TAN Qi1,XIA Lin-tao1,ZHANG Jia-yan1,FAN Yu-xiang2,WANG Shu-mei1*   

  1. 1Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases,College of Traditional Chinese Medicine,Chongqing Medical University,Chongqing 400010,China;2First Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210023,China
  • Online:2024-05-28 Published:2024-05-29

Abstract:

To explore the mechanism of Jianpi Chutan Jiedu Decoction (JCJD) on lung cancer based on integrated pharmacology and experimental verification.The integrated pharmacology based research platform of traditional Chinese medicine (TCMIP) v2.0 was used to retrieve and obtain the target and function information of JCJD and lung cancer disease target and function information.The "disease prescription" association network was constructed with the help of the Chinese Medicine Association Network mining platform,and the network topology characteristics were calculated The user-defined multidimensional correlation network visualization (prescription-Chinese herbal medicine-core target-pathway-disease),gene ontology (GO) function and the path information based on the reactome database were enriched and analyzed,and the key network targets and mechanism of action of JCJD for lung cancer were found.Finally,the results of integrated pharmacology were further verified by animal experiments.A total of 53 core targets of JCJD for lung cancer were obtained;GO enrichment analysis revealed the presence of 20 items in biological processes,11 items in cellular components,and 20 items in molecular functions;11 items were obtained from the enrichment analysis of react pathway,mainly involving respiratory electron transport,TP53 regulates metabolic genes,SUMOylation of intracellular receptors,interleukin-4 and interleukin-13 pathways and other signaling pathways.The results of animal experiments showed that compared with the model group,the content of lactic acid in tumor tissue in the combined group was significantly decreased (P<0.05).The combined group could significantly increase the average optical density of phosphatase and tensin homolog (PTEN) protein in tumor tissue (P<0.05),and reduce the average optical density of pyruvate kinase M2 (PKM2) and hexokinase 2 (HK2) protein (P<0.05);Compared with the model group,the combined group could significantly increase the expression of tumor suppressor protein (P53),PTEN mRNA and protein in tumor tissues (P<0.01,P<0.05),and reduce the expression of TP53 induced glycolysis and apoptosis regulator (TIGAR),glucose transporter 1 (GLUT1),PKM2,HK2 mRNA and protein in tumor tissues (P<0.01).In conclusion,JCJD can down regulate glucose metabolism by regulating metabolic genes through TP53,thereby inhibiting the proliferation of lung cancer.

Key words: integrated pharmacology, experimental validation, Jianpi Chutan Jiedu Decoction, lung cancer, TP53, metabolism

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