近年来,中药因其低毒高效的特性受到诸多学者的广泛关注。然而,成分复杂,作用靶点多,作用机制不明确使中药的发展极大受限。细胞代谢组学作为代谢组学一个新的研究方向,将研究系统从生物整体水平缩小到细胞整体水平,可直观反映药物刺激对某种细胞代谢的直接影响,从而更直接地体现中药作用及更有针对性地解释中药作用机制。本文对借助细胞代谢组学探索中药作用机制的概况进行综述,以期为中药作用机制探索提供参考。 In recent years, traditional Chinese medicine has been widely concerned by many scholars due to its low toxicity and high efficiency. However, the development of traditional Chinese medicine is greatly restricted owing to its complex composition, numerous targets, and unclear mechanism. As a new research direction of metabolomics, cell metabolomics narrows the research system from the overall level of biology to the overall level of cells, which can intuitively reflect the direct impact of drug stimulation on the metabolism of a certain cell, so as to more directly reflect the effects and explain the mechanism of Chinese medicines in a more targeted manner. This paper reviews the general situation of exploring the mechanism of traditional Chinese medicine by means of cell metabolomics, in order to provide reference for the exploration of the mechanism of traditional Chinese medicine.
细胞代谢组学,中药,作用机制, Cell Metabolomics Traditional Chinese Medicine Mechanism摘要
Research Overview of Cell Metabonomics in the Mechanism of Traditional Chinese Medicine
Jing Yuan, Yufeng Xia*
Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing Jiangsu
Received: Apr. 13th, 2022; accepted: May 10th, 2022; published: May 18th, 2022
ABSTRACT
In recent years, traditional Chinese medicine has been widely concerned by many scholars due to its low toxicity and high efficiency. However, the development of traditional Chinese medicine is greatly restricted owing to its complex composition, numerous targets, and unclear mechanism. As a new research direction of metabolomics, cell metabolomics narrows the research system from the overall level of biology to the overall level of cells, which can intuitively reflect the direct impact of drug stimulation on the metabolism of a certain cell, so as to more directly reflect the effects and explain the mechanism of Chinese medicines in a more targeted manner. This paper reviews the general situation of exploring the mechanism of traditional Chinese medicine by means of cell metabolomics, in order to provide reference for the exploration of the mechanism of traditional Chinese medicine.
Keywords:Cell Metabolomics, Traditional Chinese Medicine, Mechanism
袁 静,夏玉凤. 细胞代谢组学在中药作用机制中的研究概况Research Overview of Cell Metabonomics in the Mechanism of Traditional Chinese Medicine[J]. 药物资讯, 2022, 11(03): 216-223. https://doi.org/10.12677/PI.2022.113027
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<br>https://doi.org/10.1002/cam4.2108Liu, Y., Yang, S., Wang, K., Lu, J., Bao, X., Wang, R., Qiu, Y., Wang, T. and Yu, H. (2020) Cellular Senescence and Cancer: Focusing on Traditional Chinese Medicine and Natural Products. Cell Proliferation, 53, Article ID: e12894.
<br>https://doi.org/10.1111/cpr.12894Wang, K., Chen, Q., Shao, Y., Yin, S., Liu, C., Liu, Y., Wang, R., Wang, T., Qiu, Y. and Yu, H. (2021) Anticancer Activities of TCM and Their Active Components against Tumor meTastasis. Bio-medicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 133, Article ID: 111044. <br>https://doi.org/10.1016/j.biopha.2020.111044Chen, Y., Si, L., Zhang, J., Yu, H., Liu, X., Chen, Y. and Wu, Y. (2021) Uncovering the Antitumor Effects and Mechanisms of Shikonin against Colon Cancer on Comprehensive Analysis. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 82, Article ID: 153460. <br>https://doi.org/10.1016/j.phymed.2021.153460Wang, X.X., Yu, P.C. and Li, J. (2020) High-Throughput Metabolomics for Identification of Metabolic Pathways and Deciphering the Effect Mechanism of Dioscin on Rectal Cancer from Cell Metabolic Profiles Coupled with Chemometrics Analysis. Frontiers in Pharmacology, 11, Article No. 68. <br>https://doi.org/10.3389/fphar.2020.00068Zhang, Z., Zhang, S., Yang, J., Yi, P., Xu, P., Yi, M. and Peng, W. (2020) Integrated Transcriptomic and Metabolomic Analyses to Characterize the Anti-Cancer Effects of (−)-Epigallocatechin-3-Gallate in Human Colon Cancer Cells. Toxicology and Applied Pharmacology, 401, Article ID: 115100. <br>https://doi.org/10.1016/j.taap.2020.115100Liu, J., Luo, X., Guo, R., Jing, W. and Lu, H. (2020) Cell Metabolomics Reveals Berberine-Inhibited Pancreatic Cancer Cell Viability and Metastasis by Regulating Citrate Metabo-lism. Journal of Proteome Research, 19, 3825-3836.
<br>https://doi.org/10.1021/acs.jproteome.0c00394Wang, K.X., Chen, Y.P., Lu, A.P., Du, G.H., Qin, X.M., Guan, D.G. and Gao, L. (2021) A Metabolic Data-Driven Systems Pharmacology Strategy for Decoding and Validating the Mechanism of Compound Kushen Injection against HCC. Journal of Ethnopharmacology, 274, Article ID: 114043. <br>https://doi.org/10.1016/j.jep.2021.114043Wu, H., Cheng, H., Luo, S., Peng, C., Zhou, A., Chen, Z., Wu, H. and Li, Q. (2022) Use of cellular metabolomics and Lipidomics to Decipher the Mechanism of Huachansu Injec-tion-Based Intervention against Human Hepatocellular Carcinoma Cells. Journal of Pharmaceutical and Biomedical Analysis, 212, Article ID: 114654.
<br>https://doi.org/10.1016/j.jpba.2022.114654Sun, H., Zhang, A.H., Liu, S.B., Qiu, S., Li, X.N., Zhang, T.L., Liu, L. and Wang, X.J. (2018) Cell Metabolomics Identify Regulatory Pathways and Targets of Magnoline against Pros-tate Cancer. Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 1102-1103, 143-151.
<br>https://doi.org/10.1016/j.jchromb.2018.10.017王建雄. 中药神经保护作用的研究概述[J]. 世界最新医学信息文摘, 2015, 15(95): 53-55.Gao, L., Zhou, F., Wang, K.X., Zhou, Y.Z., Du, G.H. and Qin, X.M. (2020) Bai-calein Protects PC12 Cells from Aβ25–35-Induced Cytotoxicity via Inhibition of Apoptosis and Metabolic Disorders. Life Sciences, 248, Article ID: 117471.
<br>https://doi.org/10.1016/j.lfs.2020.117471Zhang, Y., Yao, Y., Shi, X., Fan, J., Huang, T., Wen, J. and Zhou, T. (2019) Combination of Cell Metabolomics and Pharmacology: A Novel Strategy to Investigate the Neuroprotective Effect of Zhi-zi-chi Decoction. Journal of Ethnopharmacology, 236, 302-315. <br>https://doi.org/10.1016/j.jep.2019.03.021Sun, J., He, F., Gao, Y., Zhou, Y., Zhang, H., Huang, M. and Bi, H. (2020) Lipidomics-Based Study on the Neuroprotective effEct of Geissoschizine Methyl Ether against Oxidative Stress-Induced Cytotoxicity. Journal of Ethnopharmacology, 253, Article ID: 112636. <br>https://doi.org/10.1016/j.jep.2020.112636Sun, L., Jia, H., Ma, L., Yu, M., Yang, Y., Liu, Y., Zhang, H. and Zou, Z. (2018) Metabolic Profiling of Hypoxia/Reoxygenation Injury in H9c2 Cells Reveals the Accumulation of Phyto-sphingosine and the Vital Role of Dan-Shen in Xin-Ke-Shu. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 49, 83-94.
<br>https://doi.org/10.1016/j.phymed.2018.06.026Lan, M., Weng, M., Lin, Z., Wang, J., Zhao, F. and Qiu, B. (2021) Metabolomic Analysis of Antimicrobial Mechanism of Polysaccharides from Sparassiscrispa Based on HPLC-Q-TOF/MS. Carbohydrate Research, 503, Article ID: 108299. <br>https://doi.org/10.1016/j.carres.2021.108299Hu, L., Liu, J., Zhang, W., Wang, T., Zhang, N., Lee, Y.H. and Lu, H. (2020) Functional Metabolomics Decipher Bio-chemical Functions and Associated Mechanisms Underlie Small-Molecule Metabolism. Mass Spectrometry Reviews, 39, 417-433. <br>https://doi.org/10.1002/mas.21611郭慧, 崔扬, 王秋红, 匡海学. 基于代谢组学技术的中药复方研究近况[J]. 中国实验方剂学杂志, 2017, 23(1): 213-219.Nicholson, J.K., Connelly, J., Lindon, J.C. and Holmes, E. (2002) Metabonomics: A Platform for Studying Drug Toxicity and Gene Function. Nature Reviews Drug discovery, 1, 153-161. <br>https://doi.org/10.1038/nrd728Fiehn, O., Kopka, J., Dörmann, P., Altmann, T., Trethewey, R.N. and Willmitzer, L. (2000) Metabolite Profiling for Plant Functional Genomics. Nature Biotechnology, 18, 1157-1161. <br>https://doi.org/10.1038/81137吴泽明, 江峥, 陈伟. 高分辨质谱技术视野下的细胞代谢组学研究策略[J]. 生命的化学, 2014, 34(2): 221-224.高山山. 基于UPLC Q-TOF/MS的丹参中单体化合物抗炎作用的代谢组学研究[D]: [硕士学位论文]. 北京: 北京中医药大学中药学院, 2017.Vuckovic, D. (2012) Cur-rent Trends and Challenges in Sample Preparation for Global Metabolomics Using Liquid Chromatography-Mass Spec-trometry. Analytical and Bioanalytical Chemistry, 403, 1523-1548.
<br>https://doi.org/10.1007/s00216-012-6039-y贾孟琪. 玉屏风复方活性物质基础及抗炎机制研究[D]: [硕士学位论文]. 上海: 上海交通大学药学院, 2016.王斯婷, 李晓娜, 王皎, 凌笑梅. 代谢组学及其分析技术[J]. 药物分析杂志, 2010, 30(9): 1792-1799.黄逸馨. 非靶向代谢组学研究LPS刺激的奶牛乳腺上皮细胞代谢变化[D]: [硕士学位论文]. 四川: 四川农业大学动物医学院, 2018.Wang, J., Guo, C., Wei, Z., He, X., Kou, J., Zhou, E., Yang, Z. and Fu, Y. (2016) Morin Suppresses Inflammatory Cytokine Expression by Downregulation of Nu-clear Factor-κB and Mitogen-Activated Protein Kinase (MAPK) Signaling Pathways in Lipopolysaccharide-Stimulated Primary Bovine Mammary Epithelial Cells. Journal of dairy science, 99, 3016-3022. <br>https://doi.org/10.3168/jds.2015-10330Abdul-Hamid, N.A., Abas, F., Ismail, I.S., Tham, C.L., Maulidiani, M., Mediani, A., Swarup, S., &Umashankar, S. (2019) 1H-NMR-Based Metabolomics to Investigate the Effects of Phoenix dactylifera Seed Extracts in LPS-IFN-γ-Induced RAW 264.7 Cells. Food Research International, 125, Article ID: 108565.
<br>https://doi.org/10.1016/j.foodres.2019.108565Li, T., Wei, Z., &Kuang, H. (2021) UPLC-orbitrap-MS-Based Metabolic Profiling of HaCaT Cells Exposed to Withanolides Extracted from Datura metel L.: Insights from an untar-geted Metabolomics. Journal of Pharmaceutical and Biomedical Analysis, 199, Article ID: 113979. <br>https://doi.org/10.1016/j.jpba.2021.113979Yan, J.J., Du, G.H., Qin, X.M. and Gao, L. (2020) Baicalein At-tenuates the Neuroinflammation in LPS-Activated BV-2 Microglial Cells through Suppression of Pro-Inflammatory Cy-tokines, COX2/NF-κB Expressions and Regulation of Metabolic Abnormality. International Immunopharmacology, 79, Article ID: 106092.
<br>https://doi.org/10.1016/j.intimp.2019.106092Cambeiro-Pérez, N., González-Gómez, X., González-Barreiro, C., Pérez-Gregorio, M.R., Fernandes, I., Mateus, N., de Freitas, V., Sánchez, B. and Martínez-Carballo, E. (2021) Metabolomics Insights of the Immunomodulatory Activities of Phlorizin and Phloretin on Human THP-1 Macrophages. Molecules, 26, Article No. 787.
<br>https://doi.org/10.3390/molecules26040787Chen, J., Tang, C., Zhou, Y., Zhang, R., Ye, S., Zhao, Z., Lin, L. and Yang, D. (2020) Anti-Inflammatory Property of the Essential Oil from Cinnamomum camphora (Linn.) Presl Leaves and the Evaluation of Its Underlying Mechanism by Using Metabolomics Analysis. Molecules, 25, Article No. 4796. <br>https://doi.org/10.3390/molecules25204796Wang, D., Zhou, L., Zhou, H. and Hou, G. (2021) Chemi-cal Composition and Anti-Inflammatory Activity of n-Butanol Extract of Piper sarmentosum Roxb. in the Intestinal Por-cine Epithelial Cells (IPEC-J2). Journal of Ethnopharmacology, 269, Article ID: 113723. <br>https://doi.org/10.1016/j.jep.2020.113723Lau, H., Ni, N., Dayal, H., Lim, S.Y., Ren, Y. and Li, S.F. (2021) Evaluation of Anti-Inflammatory Effects of Celery Leaf and Stem Extracts in LPS-Induced RAW 264.7 Cells Using Ni-tric Oxide Assay and LC-MS Based Metabolomics. Current Issues in Molecular Biology, 43, 1876-1888. <br>https://doi.org/10.3390/cimb43030131Zhang, K., Pace, S., Jordan, P.M., Peltner, L.K., Weber, A., Fischer, D., Hofstetter, R.K., Chen, X. and Werz, O. (2021) Beneficial Modulation of Lipid Mediator Biosynthesis in Innate Immune Cells by Antirheumatic Tripterygium wilfordii Glycosides. Biomolecules, 11, Article No. 746. <br>https://doi.org/10.3390/biom11050746Xiang, Y., Guo, Z., Zhu, P., Chen, J. and Huang, Y. (2019) Traditional Chinese Medicine as a Cancer Treatment: Modern Perspectives of Ancient but Advanced Science. Cancer medicine, 8, 1958-1975.
<br>https://doi.org/10.1002/cam4.2108Liu, Y., Yang, S., Wang, K., Lu, J., Bao, X., Wang, R., Qiu, Y., Wang, T. and Yu, H. (2020) Cellular Senescence and Cancer: Focusing on Traditional Chinese Medicine and Natural Products. Cell Proliferation, 53, Article ID: e12894.
<br>https://doi.org/10.1111/cpr.12894Wang, K., Chen, Q., Shao, Y., Yin, S., Liu, C., Liu, Y., Wang, R., Wang, T., Qiu, Y. and Yu, H. (2021) Anticancer Activities of TCM and Their Active Components against Tumor meTastasis. Bio-medicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 133, Article ID: 111044. <br>https://doi.org/10.1016/j.biopha.2020.111044Chen, Y., Si, L., Zhang, J., Yu, H., Liu, X., Chen, Y. and Wu, Y. (2021) Uncovering the Antitumor Effects and Mechanisms of Shikonin against Colon Cancer on Comprehensive Analysis. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 82, Article ID: 153460. <br>https://doi.org/10.1016/j.phymed.2021.153460Wang, X.X., Yu, P.C. and Li, J. (2020) High-Throughput Metabolomics for Identification of Metabolic Pathways and Deciphering the Effect Mechanism of Dioscin on Rectal Cancer from Cell Metabolic Profiles Coupled with Chemometrics Analysis. Frontiers in Pharmacology, 11, Article No. 68. <br>https://doi.org/10.3389/fphar.2020.00068Zhang, Z., Zhang, S., Yang, J., Yi, P., Xu, P., Yi, M. and Peng, W. (2020) Integrated Transcriptomic and Metabolomic Analyses to Characterize the Anti-Cancer Effects of (−)-Epigallocatechin-3-Gallate in Human Colon Cancer Cells. Toxicology and Applied Pharmacology, 401, Article ID: 115100. <br>https://doi.org/10.1016/j.taap.2020.115100Liu, J., Luo, X., Guo, R., Jing, W. and Lu, H. (2020) Cell Metabolomics Reveals Berberine-Inhibited Pancreatic Cancer Cell Viability and Metastasis by Regulating Citrate Metabo-lism. Journal of Proteome Research, 19, 3825-3836.
<br>https://doi.org/10.1021/acs.jproteome.0c00394Wang, K.X., Chen, Y.P., Lu, A.P., Du, G.H., Qin, X.M., Guan, D.G. and Gao, L. (2021) A Metabolic Data-Driven Systems Pharmacology Strategy for Decoding and Validating the Mechanism of Compound Kushen Injection against HCC. Journal of Ethnopharmacology, 274, Article ID: 114043. <br>https://doi.org/10.1016/j.jep.2021.114043Wu, H., Cheng, H., Luo, S., Peng, C., Zhou, A., Chen, Z., Wu, H. and Li, Q. (2022) Use of cellular metabolomics and Lipidomics to Decipher the Mechanism of Huachansu Injec-tion-Based Intervention against Human Hepatocellular Carcinoma Cells. Journal of Pharmaceutical and Biomedical Analysis, 212, Article ID: 114654.
<br>https://doi.org/10.1016/j.jpba.2022.114654Sun, H., Zhang, A.H., Liu, S.B., Qiu, S., Li, X.N., Zhang, T.L., Liu, L. and Wang, X.J. (2018) Cell Metabolomics Identify Regulatory Pathways and Targets of Magnoline against Pros-tate Cancer. Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences, 1102-1103, 143-151.
<br>https://doi.org/10.1016/j.jchromb.2018.10.017王建雄. 中药神经保护作用的研究概述[J]. 世界最新医学信息文摘, 2015, 15(95): 53-55.Gao, L., Zhou, F., Wang, K.X., Zhou, Y.Z., Du, G.H. and Qin, X.M. (2020) Bai-calein Protects PC12 Cells from Aβ25–35-Induced Cytotoxicity via Inhibition of Apoptosis and Metabolic Disorders. Life Sciences, 248, Article ID: 117471.
<br>https://doi.org/10.1016/j.lfs.2020.117471Zhang, Y., Yao, Y., Shi, X., Fan, J., Huang, T., Wen, J. and Zhou, T. (2019) Combination of Cell Metabolomics and Pharmacology: A Novel Strategy to Investigate the Neuroprotective Effect of Zhi-zi-chi Decoction. Journal of Ethnopharmacology, 236, 302-315. <br>https://doi.org/10.1016/j.jep.2019.03.021Sun, J., He, F., Gao, Y., Zhou, Y., Zhang, H., Huang, M. and Bi, H. (2020) Lipidomics-Based Study on the Neuroprotective effEct of Geissoschizine Methyl Ether against Oxidative Stress-Induced Cytotoxicity. Journal of Ethnopharmacology, 253, Article ID: 112636. <br>https://doi.org/10.1016/j.jep.2020.112636Sun, L., Jia, H., Ma, L., Yu, M., Yang, Y., Liu, Y., Zhang, H. and Zou, Z. (2018) Metabolic Profiling of Hypoxia/Reoxygenation Injury in H9c2 Cells Reveals the Accumulation of Phyto-sphingosine and the Vital Role of Dan-Shen in Xin-Ke-Shu. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 49, 83-94.
<br>https://doi.org/10.1016/j.phymed.2018.06.026Lan, M., Weng, M., Lin, Z., Wang, J., Zhao, F. and Qiu, B. (2021) Metabolomic Analysis of Antimicrobial Mechanism of Polysaccharides from Sparassiscrispa Based on HPLC-Q-TOF/MS. Carbohydrate Research, 503, Article ID: 108299. <br>https://doi.org/10.1016/j.carres.2021.108299