DOI QR코드

DOI QR Code

형개 추출물의 시스템 약리학적 분석과 비소세포폐암세포에 대한 증식 억제효과

Systems Pharmacological Approach to Identification of Schizonepeta teunifolia Extract via Active Ingredients Analysis and Cytotoxicity Effect on A549 Cell Lines

  • 양가람 (부산대학교 한의학전문대학원 약물의학부) ;
  • 추지은 ((주)비체담 기업부설연구소) ;
  • 김윤숙 (부산대학교 장수웰빙연구소) ;
  • 안원근 (부산대학교 한의학전문대학원 약물의학부)
  • Ga Ram Yang (Department of Pharmacology, College of Korean Medicine, Pusan National University) ;
  • Ji Eun Choo (Research and Development Institute, Bichedam Co., Ltd.) ;
  • Youn Sook Kim (Research Institute for Longevity and Well-Being, Pusan National University) ;
  • Won Gun Ahn (Department of Pharmacology, College of Korean Medicine, Pusan National University)
  • 투고 : 2024.02.16
  • 심사 : 2024.03.17
  • 발행 : 2024.03.27

초록

Objectives : This study aimed to predict the effectiveness and potential of Schizonepeta tenuifolia as an anticancer treatment for non-small cell lung cancer through network-based pharmacology and cellular experiment. Methods : To identify the major bioactive compounds in Schizonepeta tenuifolia, we used the Traditional Chinese Medicine Systems. The target genes for the cancer treatment were selected using the UniProt database and the networked using Cytoscape. We performed functional enrichment analysis based on the Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes Pathways to predict the mechanisms. To investigate the effect of Schizonepeta tenuifolia on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with different concentrations of the drug and used the MTT assay for cell viability. Results : Research has shown that the most effective mechanism of active compounds from Schizonepeta tenuifolia is through the pathway of cancer. The results of the network pharmacology analysis indicate that Schizonepeta tenuifolia has potential medicinal value as an adjuvant in anticancer treatment. The concentration-dependent inhibition of cell viability was observed on A549 cells. Furthermore, synergistic anticancer activity with Doxorubicin was also observed. Conclusions : Through a network pharmacological approach, Schizonepeta tenuifolia was predicted to have potential as an anticancer agent, and its efficacy was experimentally demonstrated using A549 cells. These findings suggest that Schizonepeta tenuifolia is a promising candidate for future research.

키워드

과제정보

This research was supported by (Basic Science Research Program) through the (National Research Foundation of Korea [NRF]) funded by the (Ministry of Education) under grant (NRF-2021R1I1A 1A01058697).

참고문헌

  1. Kapp FG, Sommer A, Kiefer T, Dolken G, Haendler B. 5-alpha-reductase type I (SRD5A1) is up-regulated in non-small cell lung cancer but does not impact proliferation, cell cycle distribution or apoptosis. Cancer Cell Int. 2012 ; 12(1) : 1. https://doi.org/10.1186/1475-2867-12-1
  2. Addeo A, Passaro A, Malapelle U, Banna GL, Subbiah V, Friedlaender A. Immunotherapy in non-small cell lung cancer harbouring driver mutations. Cancer Treat Rev. 2021 ; 96 : 102179. https://doi.org/10.1016/j.ctrv.2021.102179
  3. Suda M, Katsuumi G, Tchkonia T, Kirkland JL, Minamino T. Potential clinical implications of senotherapies for cardiovascular disease. Circ J. 2024 ; 88(3) : 277-284. https://doi.org/10.1253/circj.CJ-23-0657
  4. Kim HJ, Park SR, Ha HJ, Kim YS, Lee BK, Ahn WK. Systemic analysis of antibacterial and pharmacological functions of scutellariae radix. JPPKM. 2020 ; 34(4) : 184-90. https://doi.org/10.15188/kjopp.2020.08.34.4.184
  5. Kim HK, Lee AY, Lee HW, Cheon JM, Choi JH, Shin JW, et al. Quantitative analysis of pulegone in Schizonepeta tenuifolia Briq. Applied Biological Chemistry. 2006 ; 49(2) : 125-8.
  6. Fung D, Lau CB. Schizonepeta tenuifolia: chemistry, pharmacology, and clinical applications. J Clin Pharmacol. 2002 ; 42(1) :30-6. https://doi.org/10.1177/0091270002042001003
  7. Ru J, Li P, Wang J, Zhou W, Li B, Huang C, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014 ; 6 : 13. https://doi.org/10.1186/1758-2946-6-13
  8. Hubatsch I, Ragnarsson EG, Artursson P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat Protoc. 2007 ; 2(9) : 2111-9. https://doi.org/10.1038/nprot.2007.303
  9. Han JA, Choo JE., Shon JW, Kim YS, Suh SY, An WG. Systemic analysis of antibacterial and pharmacological functions of anisi stellati fructus. Journal of Life Science, 2019 ; 29(2) : 181-90. https://doi.org/10.5352/JLS.2019.29.2.181
  10. Lee DK, Choi MS, Shim K, Kwon OW, Son SH. The stability and mutagenecity of β-sitosterol glycoside, antimicrobial compound from schima wallichii sp. liukiuensis. The Journal of Applied Pharmacology. 1999 ; 7(3) : 204-9.
  11. Li K, Yuan D, Yan R, Meng L, Zhang Y, Zhu K. Stigmasterol exhibits potent antitumor effects in human gastric cancer cells mediated via inhibition of cell migration, cell cycle arrest, mitochondrial mediated apoptosis and inhibition of JAK/STAT signalling pathway. J BUON. 2018 ; 23(5) : 1420-5.
  12. Lin Y, Shi R, Wang X, Shen HM. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets. 2008 ; 8(7) : 634-46. https://doi.org/10.2174/156800908786241050
  13. Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Lett. 2008 ; 269(2) : 315-25. https://doi.org/10.1016/j.canlet.2008.03.046
  14. Torres K, Horwitz SB. Mechanisms of Taxol-induced cell death are concentration dependent. Cancers Res. 1998 ; 58(16) : 3620-6. https://doi.org/10.1016/j.canlet.2008.03.046
  15. Poornima P, Kumar VB, Weng CF, Padma VV. Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells. Food Chem Toxicol. 2014 ; 68 : 87-98. https://10.1016/j.fct.2014.03.008
  16. Yang HY, Baek SM, Lim YT, Park SH, Lee JH, Lee SC. Effects of far-infrared irradiation on the antioxidant and tyrosinase inhibitory activities of extracts from Schizonepeta tenuifolia. Journal of the Korean Society of Food Science and Nutrition. 2013 ; 42(9) :1357-62. https://doi.org/10.3746/jkfn.2013.42.9.1357
  17. Choi YY, Kim MH, Lee H, Jo SY, Yang WM. (R)-(+)-pulegone suppresses allergic and inflammation responses on 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice model. J Dermatol Sci. 2018 ; 91(3) : 292-300. https://doi.org/10.1016/j.jdermsci.2018.06.002
  18. Sun J. D-Limonene: safety and clinical applications. Altern Med Rev. 2007 ; 12(3) : 259-64.
  19. Park JH, Hong SU. The effect of hyunggaeyyungyo-tang of suppression of inos production on mice with allergic rhinitis. The Journal of Korean Oriental Medical Ophthalmology&Otolaryngology&Dermatology. 2012 ; 25(1) : 12-21. https://doi.org/10.6114/JKOOD.2012.25.1.012
  20. Park GH, Lim TH, Park HS. Effects of hyeongbangpaedok-san (HBPDS) on allergic contact dermatitis (ACD) induced by DNFB in mice. Journal of Sasang Constitutional Medicine. 2014 ; 26(2) : 180-93. https://doi.org/10.7730/JSCM.2014.26.2
  21. Kang YH. Effects of putative anticancer herb drugs on rat natural killer (NK) cell activity. JKM. 1987 ; 8(1) : 53-74.
  22. Cho SI. Regulatory mechanism of Schizonepeta tenuifolia Briquet on HMC-1 mast cells: microarray analysis. Kyung Hee University, Seoul, 2009. Available from: https://www.riss.kr/search/detail/DetailView.do?p_mat_type=be54d9b8bc7cdb09&control_no=93df5c95c0800b77ffe0bdc3ef48d419&outLink=N
  23. Choi YY, Kim MH, Kim JH, Jung HS, Sohn Y, Choi YJ, et al. Schizonepeta tenuifolia inhibits the development of atopic dermatitis in mice. Phytother Res. 2013 ; 27(8) : 1131-5. https://doi.org/10.1002/ptr.4833
  24. Shin TY, Jeong HJ, Jun SM, Chae HJ, Kim HR, Baek SH, et al. Effect of Schizonepeta tenuifolia extract on mast cell-mediated immediate-type hypersensitivity in rats. Immunopharmacol Immunotoxicol. 1999 ; 21(4) : 705-15. https://doi.org/10.3109/08923979909007136
  25. Song DU, Heo J, Lee S, Kim JH, Lee B, Min JH, et al. Effects of Schizonepeta Spica water extrect on the OVA-induced BALB/c mice model of allergic rhinitis. Kor. J. Herbology. 2015 ; 30(6) : 39-46. https://doi.org/10.6116/kjh.2015.30.6.39
  26. Ng YC, Kim YW, Lee JS, Lee SJ, Song MJ. Antiviral activity of Schizonepeta tenuifolia Briquet against noroviruses via induction of antiviral interferons. J Microbiol. 2018 ; 56(9) : 683-9. https://doi.org/10.1007/s12275-018-8228-7
  27. Fan JX, Wang S, Meng XS, Bao YR, Li TJ. Study of cancer cell apoptosis induced by Schizonepeta tenuifolia with microfluidic chip technology. Yao Xue Xue Bao. 2017 ; 52(1) : 126-31.