생명과학회지 (Journal of Life Science)

  • 제29권2호
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  • Pages.181-190
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  • 2019
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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대회향의 시스템 약리학적 분석과 항균작용

Systemic Analysis of Antibacterial and Pharmacological Functions of Anisi Stellati Fructus

  • 한정아 (부산대학교 한의학전문대학원) ;
  • 추지은 (부산대학교 한의학전문대학원) ;
  • 손지원 (부산대학교 한의학전문대학원) ;
  • 김윤숙 (부산대학교 의학전문대학원 의과학과) ;
  • 서수연 (옥포한의원) ;
  • 안원근 (부산대학교 한의학전문대학원)
  • Han, Jeong A (School of Korean Medicine, Pusan National University) ;
  • Choo, Ji Eun (School of Korean Medicine, Pusan National University) ;
  • Shon, Jee Won (School of Korean Medicine, Pusan National University) ;
  • Kim, Youn Sook (School of Medicine, Pusan National University) ;
  • Suh, Su Yeon (Okpo Korean Medicine Clinic) ;
  • An, Won Gun (School of Korean Medicine, Pusan National University)
  • 투고 : 2019.01.15
  • 심사 : 2019.02.13
  • 발행 : 2019.02.28
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초록

시스템 약리학적 분석을 통해 대회향(Anisi Stellati Fructus)의 활성성분 스크리닝, 표적유전자 확보 및 관련 질병과의 네트워크를 구축한 후 대회향의 항균작용을 중점적으로 분석하였다. Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database 와 Analysis Platform을 통해 대회향의 잠재적 활성성분 49개를 확보하였으며, 그 중 설정한 조건에 부합하는 9개 활성성분을 스크리닝 하였다. TCMSP Database는 활성성분의 약물 동태학적 특성 및 약물-표적-질병 간의 관련성을 네트워크 수준에서 파악할 수 있는 획기적인 in silico적 접근을 가능하게 해준다. 활성성분과 반응하는 201개의 유전자 정보를 UniProt database를 통해 확인하고, 취합한 유전자들이 관여하는 348개의 생물학적 과정을 David 6.8 Gene Functional Classification Tool에서 확보하였다. Chemokine ligand 2, Interleukin-10, Interleukin-6, Tumor Necrosis Factor를 포함한 총 47개의 유전자가 항균작용에 관여하였고 이들을 표적으로 하는 luteolin, kaempferol, quercetin 등이 대표적 항균 관련 활성성분이었다. 이와 같이 확보된 데이터는 연구 재료 선정에 정확성과 시간, 노력, 비용 절감의 효과를 제공함과 더불어 추후 실험적 증명으로 이어져 감염병의 예방과 치료 전략에 과학적인 근거를 제시할 수 있을 것이다.

The purpose of this study was to acquire the active compounds of Anisi stellati fructus (ASF) and to analyze the genes and diseases it targets, focusing on its antibacterial effects using a system pharmacological analysis approach. Active compounds of ASF were obtained through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform. This contains the pharmacokinetic properties of active compounds and related drug-target-disease networks, which is a breakthrough in silico approach possible at the network level. Gene information of targets was gathered from the UnitProt Database, and gene ontology analysis was performed using the David 6.8 Gene Functional Classification Tool. A total of 201 target genes were collected, which corresponded to the nine screened active compounds, and 47 genes were found to act on biological processes related to antimicrobial activity. The representative active compounds involved in antibacterial action were luteolin, kaempferol, and quercetin. Among their targets, Chemokine ligand2, Interleukin-10, Interleukin-6, and Tumor Necrosis Factor were associated with more than three antimicrobial biological processes. This study has provided accurate evidence while saving time and effort to select future laboratory research materials. The data obtained has provided important data for infection prevention and treatment strategies.

키워드

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Fig. 1. Workflow: the performance of systems pharmacological network analysis of Anisi Stellati Fructus (ASF), active compounds screening, target fishing, gene ontology analysis, and network constructions.

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Fig. 2. Gene Ontology analysis shows 7 biological processes. The y-axis represents the terms of biological processes, and the x-axis represents counts of target genes ( P value <0.01).

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Fig. 3. The network of Anisi Stellati Fructus,. (A) compound-target network, blue nodes ; active compounds, grey nodes ; target genes. (B) pathway-target network, red nodes ; pathway, grey nodes ; target genes.

Table 1. 9 Active compounds of Anisi Stellati Fructus (OB≧35%, caco-2≧-0.4, DL≧0.10) including additionally added anethole and SKM

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Table 2. Related targets of Anisi Stellati Fructus

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Table 2. Continued

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Table 2. Continued

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Table 2. Continued

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참고문헌

  1. Abbas, A. K., Lichtman, A. H. and Pillai, S. 2018. Cellular and Molecular Immunology, pp. 43-44, 9th ed., Elsevier, Philadelphia, USA.
  2. Boots, A. W., Haenen, G. R. and Bast, A. 2008. Health effects of quercetin: from antioxidant to nutraceutical. Eur. J. Pharmacol. 585, 325-337. https://doi.org/10.1016/j.ejphar.2008.03.008
  3. Chun, B. C. 2001. Epidermiological characteristics and ecological perspectives of zoonoses. J. Agri. Med. Community Health 26, 123-144.
  4. Donadio, S., Maffioli, S., Monciardini, P., Sosio, M. and Jabes, D. 2010. Antibiotic discovery in the twenty-first century: current trends and future perspectives. J. Antibiotics 63, 423-430. https://doi.org/10.1038/ja.2010.62
  5. Ghosh, S., Chisti, Y. and Banerjee, U. C. 2012. Production of shikimic acid. Biotechnol. Adv. 30, 1425-1431. https://doi.org/10.1016/j.biotechadv.2012.03.001
  6. Goldbout, J. P. and Glaser, R. 2006. Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J. Neuroimmune. Pharm. 1, 421-427. https://doi.org/10.1007/s11481-006-9036-0
  7. Huang, D. W., Sherman, B. T. and Lempicki, R. A. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57. https://doi.org/10.1038/nprot.2008.211
  8. Huang, D. W., Sherman, B. T. and Lempicki, R. A. 2009. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37, 1-13. https://doi.org/10.1093/nar/gkn923
  9. Huang, Y., Zhao, J., Zhou, L., Wang, J., Gong, y., Chen, X., Guo, Z., Wang, Q. and Jiang, W. 2010. Antifungal activity of the essential oil of Illicium verum fruit and its main component trans-anethole. Molecules 15, 7558-7569. https://doi.org/10.3390/molecules15117558
  10. Kang, C. I. 2011. Therapeutic strategy for the management of multi-resistant gram-negative bacterial infections. J. Kor. Med. Assoc. 54, 325-331. https://doi.org/10.5124/jkma.2011.54.3.325
  11. Kataoka, M., Hirata, K., Kunikata, T., Ushio, S., Iwaki, K., Ohashi, K., Ikeda, M. and Kurimoto, M. 2001. Antibacterial action of tryptanthrin and kaempferol, isolated from the indigo plant (Polygonum tinctorium Lour.), against Helicobacter pylori-infected Mongolian gerbils. J. Gastroenterol. 36, 5-9. https://doi.org/10.1007/s005350170147
  12. Kim, A., Im, M. and Ma, J. Y. 2014. Anisi stellati fructus extract attenuates the in vitro and in vivo metastatic and angiogenic potential of malignant cancer cells by down regulating proteolytic activity and pro-angiogenic factors. Int. J. Oncol. 45, 1937-1948. https://doi.org/10.3892/ijo.2014.2606
  13. Kint, T. J., Goldsby, R. A., Osborne, B. A. and Kuby, J. 2006. Immunology, pp. 307, A-28, A-31, 6th ed., Macmillan, New York, USA.
  14. Lee, J. Y., Kim, Y. J., Kim, H. J., Lee, M. W. and Park, W. S. 2012. Effect of Anisi Stellati Fructus extract on hydrogen peroxide production in RAW 264.7 mouse macrophage. J. Physiol. Pathol. Kor. Med. 26, 301-305.
  15. Lee, S. H. 2008. Epidemics, Human Security, and National Security. Int. Area Studies 12, 229-246. https://doi.org/10.18327/jias.2008.10.12.3.229
  16. Lim, Y. H., Kim, I. H. and Seo, J. J. 2007. In vitro activity of kaempferol isolated from the impatiens balsamina alone and in combination with erythromycin or clindamycin against Propionibacterium acnes. J. Microbiol. 45, 473-477.
  17. Nabavi, S. F., Braidy, N., Gortzi, O., Sobarzo-Sanchez, E., Daglia, M., Skalicka-Woźniak, K. and Nabavi, S. M. 2015. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. Brain Res. Bull. 119, 1-11. https://doi.org/10.1016/j.brainresbull.2015.09.002
  18. Suh, S. Y. and An, W. G. 2017. Systems pharmacological approach of Pulsatillae Radix on treating Crohn's Disease. Evid. Based Complement Alternat. Med. 2017, 4198035.
  19. Wang, G. W., Hu, W. T., Huang, B. K. and Qin, L. P. 2011. Illicium verum: a review on its botany, traditional use, chemistry and pharmacology. J. Ethnopharmacol. 136, 10-20. https://doi.org/10.1016/j.jep.2011.04.051
  20. Wang, Q. and Xie, M. 2010. Antibacterial activity and mechanism of luteolin on Staphylococcus aureus. Wei Sheng Wu Xue Bao 50, 1180-1184.
  21. Yang, X., Zhang, W., Zhao, Z., Li, N., Mou, Z., Sun, D., Cai, Y., Wang, W. and Lin, Y. 2017. Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and anticancer materials. J. Inorg. Biochem. 167, 36-48. https://doi.org/10.1016/j.jinorgbio.2016.11.023