DOI QR코드

DOI QR Code

Effect of Methanol Extract Concentration on the Anti-oxidative Activity and Toxicity of Evodiae Fructus to AGS Cells

오수유의 메탄올 추출 농도에 따른 항산화와 AGS세포에 대한 독성 효과

  • Yang, Ji Yeong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Byeon, Hwiyong (School of Oriental Medicine and Bio Convergence Sciences, Semyung University) ;
  • Kim, Jin Woo (School of Oriental Medicine and Bio Convergence Sciences, Semyung University) ;
  • Kim, Sa Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Lee, Pyeongjae (School of Industrial Bio-pharmaceutical Science, Semyung University)
  • 양지영 (연세대학교 보건과학대학 임상병리학과) ;
  • 변휘용 (세명대학교 한방바이오융합과학부) ;
  • 김진우 (세명대학교 한방바이오융합과학부) ;
  • 김사현 (세명대학교 임상병리학과) ;
  • 이평재 (세명대학교 바이오제약산업학부)
  • Received : 2020.08.03
  • Accepted : 2020.08.26
  • Published : 2020.08.31

Abstract

Evodiae Fructus is the dried unripe fruit of Evodia rutaecarpa, and has traditionally been used for treating stomachache and diarrhea. Evodiamine and rutaecarpine, the major biologically active compounds of Evodiae Fructus, are reported to have anti-oxidative and anti-inflammatory effects, as well as inhibit proliferation and metastasis of various cancer cells. The current study investigates the anti-oxidative and anti-cancer effects of the Evodiae Fructus extract, considering varying concentrations of methanol extraction (40, 80, and 95%). High contents of total phenolic compounds were determined in the order of extracts 80, 95, and 40%. Evaluating contents of the 95, 80, and 40% extracts revealed 36.77, 7.29, and 1.86 ㎍/mg evodiamine, respectively, and 53.02, 17.16, and 3.79 ㎍/mg rutaecarpine, respectively, with the highest content of both compounds obtained in the 95% extract. DPPH radical scavenging activity was observed to be inversely proportional to the contents of total phenolic compounds, with decreasing SC50 values obtained in the order 80, 95, and 40% extract. The 95 and 80% extracts exerted toxicity to AGS gastric cancer cells, but the 40% extract was non-toxic. Evodiamine is a known anti-cancer agent, and could be responsible for the observed toxicity. Cleavage of PARP, and Caspase-3, -7, -8 and -9 was observed in the 95% extract-treated AGS cells, indicating that cell toxicity exerted by the 95% extract could be attributed to apoptosis.

Keywords

References

  1. Bezek K, Kurincic M, Knauder E, Klancnik A, Raspor P, Bucar F, Mozina SS. 2016. Attenuation of adhesion, biofilm formation and quorum sensing of Campylobacter jejuni by Euodia ruticarpa. Phytother Res., 30:1527-1532 https://doi.org/10.1002/ptr.5658
  2. Cai QY, Li WR, Wei JJ, Mi SQ, Wang NS. 2014. Antinociceptive activity of aqueous and alcohol extract of Evodia rutaecarpa. Indian J Pharm Sci., 76:235-239
  3. Chien CC, Wu MS, Shen SC, Ko CH, Chen CH, Yang LL, Chen YC. 2014. Activation of JNK contributes to evodiamine-induced apoptosis and G2/M arrest in human colorectal carcinoma cells: a structure-activity study of evodiamine. PLoS One, 9:e99729 https://doi.org/10.1371/journal.pone.0099729
  4. Choi YH, Shin EM, Kim YS, Cai XF, Lee JJ, Kim HP. 2006. Anti-inflammatory principles from the fruits of Evodia rutaecarpa and their cellular action mechanisms. Arch Pharm Res., 29:293-297 https://doi.org/10.1007/BF02968573
  5. Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol Pathol., 35:495-516 https://doi.org/10.1080/01926230701320337
  6. Jin SW, Hwang YP, Choi CY, Kim HG, Kim SJ, Kim Y, Chung YC, Lee KJ, Jeong TC, Jeong HG. 2017. Protective effect of rutaecarpine against t-BHP-induced heptotoxicity by upregulating antioxidant enzymes via the CaMKII-Akt and Nrf2/ARE pathways. Food Chem Toxicol., 100:138-148 https://doi.org/10.1016/j.fct.2016.12.031
  7. Ko HC, Wang YH, Liou KT, Chen CM, Chen CH, Wang WY, Chang S, Hou YC, Chen KT, Chen CF, Shen YC. 2007. Anti-inflammatory effects and mechanims of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells. Eur J Pharmacol., 555:211-217 https://doi.org/10.1016/j.ejphar.2006.10.002
  8. Lee JW, Park JH, Kim JS, Choi EY, Han SN, Seong ES, Yu CY, Kwon YS, Kim MJ. 2011. Isolation of flavonol glycoside related to antioxidant activity from Hippophae rhamnoides leaves. Korean J Medicinal Crop Sci., 19:251-256 https://doi.org/10.7783/KJMCS.2011.19.4.251
  9. Li AN, Zhang YJ, Xu XR, Chen YM, Li HB. 2014. Resources and biological activities of natural polyphenols. Nutrients, 6:6020-6047 https://doi.org/10.3390/nu6126020
  10. Liao CH, Pan SL, Guh JH, Chang YL, Pai HC, Lin CH, Teng CM. 2005. Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae Fructus, in human multiple-drug resistant breast cancer NCI/ADRRES cells in vitro and in vivo. Carcinogenesis, 26:968-975 https://doi.org/10.1093/carcin/bgi041
  11. Liao Y, Liu Y, Xia X, Shao Z, Huang C, He J, Jiang L, Tang D, Liu J, Huang H. 2020. Targeting GRP78-dependent AR-V7 protein degradation overcomes castration-resistance in prostate cancer therapy. Theranostics, 10:3366-3381 https://doi.org/10.7150/thno.41849
  12. Lin L, Ren LI, Wen L, Wang Y, Qi J. 2016. Effect of evodiamine on the proliferation and apoptosis of A549 human lung cancer cells. Mol Med Rep., 14:2832-2838 https://doi.org/10.3892/mmr.2016.5575
  13. Park E, Lee MY, Seo CS, Jang JH, Kim YU, Shin HK. 2018. Ethanol extract of Evodia rutaecarpa attenuates cell growth through caspase-dependent apoptosis in benign prostatic hyperplasia-1 cells. Nutrients, 10:523 https://doi.org/10.3390/nu10040523
  14. Rasul A, Yu B, Zhong L, Khan M, Yang H, Ma T. 2012. Cytotoxic effect of evodiamine in SGC-7901 human gastric adenocarcinoma cells via simultaneous induction of apoptosis and autophagy. Oncol Rep., 27:1481-1487 https://doi.org/10.3892/or.2012.1694
  15. Ryu MJ. 2014. Functional Activities of Evodia officinalis extract as cosmetic materials. Kor J Aesthet Cosmetol., 12:797-804
  16. Scherer R, Godoy HT. 2009. Antioxidant activity index (AAI) by the 2,2-diphenyl-1-picrylhydrazyl method. Food Chem., 112:654-658 https://doi.org/10.1016/j.foodchem.2008.06.026
  17. Yang L, Liu X, Wu D, Zhang M, Ran G, Bi Y, Huang H. 2014. Growth inhibition and induction of apoptosis in SGC-7901 human gastric cancer cell by evodiamine. Mol Med Rep., 9:1147-1152 https://doi.org/10.3892/mmr.2014.1924
  18. Yun HJ, Heo SK, Lee YT, Park WH, Park SD. 2008. Antiinflammatory effect of Evodia officinalis DODE in mouse macrophage and human vascular endothelial cells. Kor J Herbology, 23:29-38
  19. Zhang PT, Pan BY, Liao QF, Yao MC, Xu XJ, Wan JZ, Liu D, Xie ZY. 2013. Simultaneous quantification of limonin, two indolequinazoline alkaloids, and four quinolone alkaloids in Evodia rutaecarpa (Juss.) Benth HPLCDAD Method. J Anal Methods Chem., 2013:Article ID 827361
  20. Zhang YN, Yang YF, Yang XW. 2018. Blood-brain barrier permeability and neuroprotective effects of three main alkaloids from the fruits of Euodia rutaecarpa with MDCK-pHaMDR cell monolayer and PC12 cell line. Biomed Pharmacother., 98:82-87 https://doi.org/10.1016/j.biopha.2017.12.017