DOI QR코드

DOI QR Code

Anti-Inflammatory Effects of Annona muricata Leaf Ethanol Extracts

그라비올라(Annona muricata) 잎 에탄올 추출물의 항염증 효과

  • Cho, Eun-Ji (Department of Food Science and Technology, Kongju National University) ;
  • Lee, Joeng Hee (Department of Food Science and Technology, Kongju National University) ;
  • Sung, Nak-Yun (Department of Food Science and Technology, Kongju National University) ;
  • Byun, Eui-Hong (Department of Food Science and Technology, Kongju National University)
  • Received : 2017.03.21
  • Accepted : 2017.05.16
  • Published : 2017.06.30

Abstract

This study was focused on the anti-inflammatory activities of Annona muricata leaf ethanol extracts (AME). Inflammation of macrophages was induced by lipopolysaccharide (LPS) treatment, and various inflammation-mediated factors [cytokines and nitric oxide (NO)] were measured. AME treatment significantly reduced LPS-induced NO, cytokine levels [interleukin (IL)-6, tumor necrosis $factor-{\alpha}$ and $IL-1{\beta}$], and expression of inducible NO synthase and cyclooxygenase-2 in a dose-dependent manner. Mechanical studies showed that AME treatment inhibited activation of mitogen-activated protein kinase and nuclear factor $(NF)-{\kappa}B$ in macrophages treated with LPS. From these results, AME treatment strongly inhibits LPS-induced inflammation through inhibition of $NF-{\kappa}B$ activation, suggesting AME could be a potential candidate for treatment of inflammatory disease as a nutraceutical drug.

본 연구는 그라비올라 잎 에탄올 추출물(AME)의 항염증 효과에 관하여 알아보기 위하여 LPS에 의해 유도되는 대식세포 염증모델에 AME를 병용 처리하여 다양한 염증매개인자들의 분비능 및 염증억제 기전에 관하여 알아보았다. LPS의 처리에 따라 염증반응이 유도된 RAW 264.7 대식세포에 AME를 병용 처리하였을 때, NO 및 염증성 cytokine(IL-6, $TNF-{\alpha}$$IL-1{\beta}$)의 분비능이 유의적으로(P<0.05) 감소하는 것을 확인하였다. 또한, AME의 처리에 따라 염증반응의 매개인자인 iNOS 및 COX-2 발현이 유의적으로(P<0.05) 감소하는 것으로 나타났으며, 이러한 항염증 활성의 기전에 관하여 분석한 결과 염증성 단백질 발현의 전사인자인 $NF-{\kappa}B$와 MAPKs 신호전달 경로 억제를 통하여 추출물의 항염증 활성이 나타난다는 사실을 관찰할 수 있었다. 따라서 이러한 결과를 통하여 AME의 처리는 염증반응의 전사인자인 $NF-{\kappa}B$의 발현을 조절함으로써 iNOS 및 COX-2의 발현을 억제하고, 염증성 매개인자인 NO 및 cytokine(IL-6, $TNF-{\alpha}$$IL-1{\beta}$)의 분비를 억제한다고 판단된다.

Keywords

References

  1. Jeong DH, Kang BK, Kim KBWR, Kim MJ, Ahn DH. 2014. Anti-inflammatory activity of Sargassum micracanthum water extract. J Appl Biol Chem 57: 227-234. https://doi.org/10.3839/jabc.2014.036
  2. Yoon YI, Chung MY, Hwang JS, Goo TW, Ahn MY, Lee YB, Han MS, Yun EY. 2014. Anti-inflammatory effect of Oxya chinensis sinuosa ethanol extract in LPS-induced RAW 264.7 cells. J Life Sci 24: 370-376. https://doi.org/10.5352/JLS.2014.24.4.370
  3. Choi SB, Bae GS, Jo IJ, Park KC, Seo SH, Kim DG, Shin JY, Gwak TS, Lee JH, Lee GS, Park SJ, Song HJ. 2013. The anti-inflammatory effect of Lithospermum Erythrorhizon on lipopolysaccharide-induced inflammatory response in RAW 264.7 cells. Kor J Herbology 28: 67-73. https://doi.org/10.6116/kjh.2013.28.2.67
  4. Choi MW, Kim JI. 2013. Anti-inflammatory effect of ethyl acetate fraction isolated from Undaria pinnatifida on lipopolysaccharides-stimulated RAW 264.7 cells. Kor J Fish Aquat Sci 46: 384-392.
  5. Alassane W, Yanjun Z, Caux C, Brouard JP, Pousset JL, Bodo B. 2004. Annomuricatin C, a novel cyclohexapeptide from the seeds of Annona muricata. Comptes Rendus Chimie 7: 981-988. https://doi.org/10.1016/j.crci.2003.12.022
  6. Liu N, Yang HL, Wang P, Lu YC, Yang YJ, Wang L, Lee SC. 2016. Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway. J Ethnopharmacol 2: 210-217.
  7. Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. 2015. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis 16: 656-665
  8. Liu HX, Huang GR, Zhang HM, Wu JR, Yao ZJ. 2007. Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity against cancer cells. Bioorg Med Chem Lett 17: 3426-3430. https://doi.org/10.1016/j.bmcl.2007.03.084
  9. Florence NT, Benoit MZ, Jonas K, Alexandra T, Desire DD, Pierre K, Theophile D. 2014. Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous extract on streptozotocin-induced diabetic rats. J Ethnopharmacol 151: 784-790. https://doi.org/10.1016/j.jep.2013.09.021
  10. Mahibalan S, Sharma R, Vyas A, Besha SA, Begum S. 2013. Assessment of extraction techniques for total phenolics and flavonoids from Annona muricata seeds. J Indian Chem Soc 90: 2199-2205.
  11. Jeong H, Sung M, Kim Y, Ham H, Choi Y, Lee J. 2012. Anti-inflammatory activity of Salvia plebeia R. Br. leaf through heme oxygenase-1 induction in LPS-stimulated RAW264.7 macrophages. J Korean Soc Food Sci Nutr 41: 888-894. https://doi.org/10.3746/jkfn.2012.41.7.888
  12. Byun EB, Sung NY, Park JN, Yang MS, Park SH, Byun EH. 2015. Gamma-irradiated resveratrol negatively regulates LPS-induced MAPK and $NF-{\kappa}B$ signaling through TLR4 in macrophages. Int Immunopharmacol 25: 249-259. https://doi.org/10.1016/j.intimp.2015.02.015
  13. Choe SI, Park SJ, Byun SH, Lee JB, Park MK, Kim SC. 2009. Effects of Spatholobi Caulis MeOH extract on the production of NO and pro-inflammatory cytokines in LPS-activated Raw264.7 cells. Kor J Herbology 24: 21-27.
  14. Han HS. 2013. Anti-inflammatory effect of Angelicae Gigantis Radix water extract on LPS-stimulated mouse macrophages. Kor J Herbology 28: 113-119. https://doi.org/10.6116/kjh.2013.28.5.113
  15. Kim SY, Jo MJ, Hwangbo M, Back YD, Jeong TY, Cho IJ, Jee SY. 2013. Anti-inflammatory effect of Stevia rebaudiana as a results of $NF-{\kappa}B$ and MAPK inhibition. J Korean Med Ophthalmol Otolaryngol Dermatol 26: 54-64. https://doi.org/10.6114/jkood.2013.26.3.054
  16. Yoo YC, Lee GW, Cho YH. 2016. Antioxidant and anti-inflammatory effects of extracts from the flowers of Weigela subsessilis on RAW 264.7 macrophages. J Life Sci 26: 338-345. https://doi.org/10.5352/JLS.2016.26.3.338
  17. Kim DH, Lee JR, Byun SH, Shin SW, Kwon YK, Kim SC. 2006. Inhibitory effect of Stephanniae tetrandrae Radix extract on $TNF-{\alpha}$, $IL-1{\beta}$, IL-6 and nitric oxide production in lipopolysaccharide action RAW 264.7 cells. Korean J Oriental Physiol Pathol 20: 902-908.
  18. Tezuka Y, Irikawa S, Kaneko T, Banskota AH, Nagaoka T, Xiong Q, Hase K, Kadota S. 2001. Screening of Chinese herbal drug extracts for inhibitory activity on nitric oxide production and identification of an active compound of Zanthoxylum bungeanum. J Ethnopharmacol 77: 209-217. https://doi.org/10.1016/S0378-8741(01)00300-2
  19. Masferrer JL, Zweifel BS, Manning PT, Hauser SD, Leahy KM, Smith WG, Isakson PC, Seibert K. 1994. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci U S A 91: 3228-3232. https://doi.org/10.1073/pnas.91.8.3228
  20. Cobb MH, Goldsmith EJ. 2000. Dimerization in MAP-kinase signaling. Trends Biochem Sci 25: 7-9. https://doi.org/10.1016/S0968-0004(99)01508-X
  21. Caivano M. 1999. Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW264 macrophages. FEBS Lett 429: 249-253.
  22. Robinson MJ, Cobb MH. 1997. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9: 180-186. https://doi.org/10.1016/S0955-0674(97)80061-0

Cited by

  1. Anti-Inflammatory and Antioxidant Properties of Ethanol Extracts of Raw, Blanched, Steamed, and Sous-Vide Cooked Okra (Abelmoschus esculentus L.) in LPS or H2O2-Treated RAW264.7 Cells vol.11, pp.5, 2017, https://doi.org/10.3390/app11052432
  2. 섬기린초(Sedum takesimense)에서 분리된 화합물들의 RAW 264.7 Cell에 대한 항염증 효과와 여드름 원인균에 대한 항균 효과 vol.54, pp.4, 2021, https://doi.org/10.5657/kfas.2021.0552