Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Pomace of Schizandra chinensis, Schizandrin, and Gomisin A on LPS-induced Inflammatory Responses in RAW264.7 Cells

오미자 박, schizandrin 및 gomisin A에 의한 RAW264.7 세포주에서 lipopolysaccharide로 유도된 염증 반응의 억제

  • Seo, Yu-Mi (Department of Biological Sciences, Andong National University) ;
  • Kim, Hyun-Ji (Department of Biological Sciences, Andong National University) ;
  • Lee, Eun-Joo (Department of Biological Sciences, Andong National University) ;
  • Chung, Chungwook (Department of Biological Sciences, Andong National University) ;
  • Sung, Hwa-Jung (Department of Food and Nutrition, Andong National University) ;
  • Sohn, Ho-Yong (Department of Food and Nutrition, Andong National University) ;
  • Park, Jong-Yi (Gyeongbuk Institute for Bio Industry) ;
  • Kim, Jong-Sik (Department of Biological Sciences, Andong National University)
  • 서유미 (국립안동대학교 생명과학과) ;
  • 김현지 (국립안동대학교 생명과학과) ;
  • 이은주 (국립안동대학교 생명과학과) ;
  • 정정욱 (국립안동대학교 생명과학과) ;
  • 성화정 (국립안동대학교 식품영양학과) ;
  • 손호용 (국립안동대학교 식품영양학과) ;
  • 박종이 (경북바이오산업 연구원) ;
  • 김종식 (국립안동대학교 생명과학과)
  • Received : 2017.10.16
  • Accepted : 2017.12.04
  • Published : 2018.03.30
Download PDF
⟨ Previous Next ⟩

Abstract

Schizandra chinensis has been used as a traditional Chinese medicine and is known to have various bioactive components, including schizandrin and gomisin A. In the current study, we investigated the anti-inflammatory activities and their working mechanisms of ethanol extracts of pomace of Schizandra chinensis (PSC), schizandrin (SZ), and gomisin A (GA). First, we analyzed the effects of PSC on nitric oxide (NO) production and cell viabilities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results indicated that PSC dramatically reduced NO production in LPS-activated RAW264.7 cells in a dose-dependent manner without affecting cell viabilities. PSC also decreased the expression of pro-inflammatory genes iNOS and COX-2, whereas the expression of TNF-${\alpha}$ was not affected by PSC. In addition, PSC inhibited phosphorylation of p38, ERK1/2, and JNK but did not change the expression of their total protein. The results indicate that PSC can regulate LPS-induced inflammatory responses by suppressing MAPK (mitogen-activated protein kinase) signaling. We also analyzed the effects of SZ and GA on NO production and cell viabilities in RAW264.7 cells. The results showed that SZ and GA also decreased NO production in a dose-dependent manner in LPS-activated RAW 264.7 cells without affecting cell viabilities. SZ reduced the expression of iNOS, whereas GA downregulated iNOS and COX-2. Overall, these findings clarify the molecular mechanisms of the anti-inflammatory effects mediated by PSC, SZ, and GA.

오미자는 전통적인 한약재로서 schizandrin과 gomisin A와 같은 다양한 생리활성물질을 함유하고 있는 것으로 알려져 있다. 본 연구에서는 오미자 박의 에탄올 추출물(PSC)과 schizandrin (SZ) 및 gomisin A (GA)에 의한 항염증 활성 및 그들의 작용기전 연구를 수행하였다. 먼저, PSC는 LPS에 의해 염증이 유도된 RAW264.7 세포에서 세포생존율에는 영향을 미치지 않고 농도의존적으로 nitric oxide (NO) 생성을 감소시켰다. PSC는 염증유발유전자인 iNOS와 COX-2의 발현을 감소시켰으나, $TNF-{\alpha}$의 발현에는 영향을 주지 않았다. 또한 오미자 박의 에탄올 추출물은 p38, ERK1/2 및 JNK의 총 단백질의 발현에는 영향을 주지 않으면서, 그들의 인산화를 감소시켰다. 이러한 결과는 PSC가 MAPK 신호를 저해함으로써 염증 반응을 조절할 수 있음을 시사한다. 또한 SZ와 GA도 LPS에 의해 염증이 유도된 RAW264.7 세포에서 세포 생존율에 영향을 미치지 않으면서 NO 생성을 감소시켰다. SZ은 iNOS 유전자의 발현만을 감소시킨 반면, GA는 iNOS와 COX-2 두 유전자의 발현을 모두 감소시켰다. 종합적으로 이러한 연구결과는 오미자 박 추출물, schizandrin 및 gomisin A에 의해 중재되는 항염증 활성 및 작용기전을 이해하는데 도움을 줄 것이다

Keywords

References

  1. Choo, B. K., Chung, K. H., Seo, Y. B. and Roh, S. S. 2013. Antioxidant, antiinflammation and hepatoprotective activity of Schizandrae Fructus processed with differensiated steaming number. Kor. J. Herbology 28, 83-92.
  2. Ci, X., Ren, R., Xu, K., Li, H., Yu, Q., Song, Y., Wang, D., Li, R. and Deng, X. 2010. Schisantherin A exhibits anti-inflammatory properties by down-regulating NF-kappaB and MAPK signaling pathways in lipopolysaccharide-treated RAW 264.7 cells. Inflammation 33, 126-136. https://doi.org/10.1007/s10753-009-9166-7
  3. Guo, L. Y., Hung, T. M., Bae, K. H., Shin, E. M., Zhou, H. Y., Hong, Y. N., Kang, S. S., Kim, H. P. and Kim, Y. S. 2008. Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. Eur. J. Pharmacol. 591, 293-299. https://doi.org/10.1016/j.ejphar.2008.06.074
  4. Jang, J. Y. and Park, G. H. 2015. Anti-inflammatory effect of seed oil of Schisandra chinensis in the LPS-treated RAW264.7 macrophages. Kor. J. Herbology 30, 77-82.
  5. Jeong, E. J., Lee, W. J. and Kim, K. Y. 2009. Effects of Schizandra chinensis extract on the growth of intestinal bacteria related with obesity. Kor. J. Food Sci. Technol. 41, 673-680.
  6. Kim, M. S., Sung, H. J., Park, J. Y and Sohn, H. Y. 2017. Evaluation of anti-oxidant, anti-microbial and anti-thrombosis activities of fruit, seed and pomace of Schizandra chinensis Baillon. J. Life Sci. 27, 131-138. https://doi.org/10.5352/JLS.2017.27.2.131
  7. Korhonen, R., Lahti, A., Kankaanranta, H. and Moilanen, E. 2005. Nitric oxide production and signaling in inflammation. Curr. Drug Targets Inflamm. Allergy 4, 471-479. https://doi.org/10.2174/1568010054526359
  8. Lee, J. H. 2011. Quality of Sikhe incorporated with hot water extract of Omija (Schisandra chinensis Baillon) fruit. Food Eng. Prog. 15, 80-84.
  9. Maeng, O., Kim, Y. C., Kim, Y. S., Paik, S. G. and Lee, H. Y. 2002. The function and regulation of NO; Identification of a gene that is up-regulated in RAW264.7 macrophage cells by nitric oxide. Bulletin of Biotechnology Chungnam National University 8, 1-9.
  10. Morita, I. 2002. Distinct functions of COX-1 and COX-2. Prostaglandins Other Lipid Mediat. 68-69, 165-175. https://doi.org/10.1016/S0090-6980(02)00029-1
  11. Park, C., Hwang, H. J., Choi, B. T., Choi, T. H., Kim, B. W., Choi, Y. W. and Choi, Y. H. 2010. G1 arrest of the cell cycle by gomisin N, a dibenzocyclooctadiene lignan, isolated from Schizandra chinensis Baill in human leukemia U937 cells. J. Life Sci. 20, 977-982. https://doi.org/10.5352/JLS.2010.20.7.977
  12. Park, S., Shin, H. J., Shah, M., Cho, H. Y., Anwar, M. A., Achek, A., Kwon, H. K., Lee, B., Yoo, T. H. and Choi, S. 2017. TLR4/MD2 specific peptides stalled in vivo LPS-induced immune exacerbation. Biomaterials 126, 49-60. https://doi.org/10.1016/j.biomaterials.2017.02.023
  13. Park, S. Y., Park, D. J., Kim, Y. H., Kim, Y., Kim, S. G., Shon, K. J., Choi, Y. W. and Lee, S. J. 2011. Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages. Immunol. Lett. 139, 93-101. https://doi.org/10.1016/j.imlet.2011.05.007
  14. Shin, Y. R., Kim, Y. K. and Kim, K. M. The Effects of Schizandrae Fructus chloroform fraction on gene expression in liver tissue of dyslipidemic mice. J. Kor. Med. Obes. Res. 15, 111-122.
  15. Song, Y. R., Lim, B. U., Song, G. S. and Baik, S. H. Quality characteristics and antioxidant activity of Makgeolli supplemented with Omija berries (Schizandra chinensis Baillon). Kor. J. Food Sci. Technol. 47, 328-335.
  16. Szopa, A., Ekiert, R. and Ekiert, H. 2017. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem. Rev. 16, 195-218. https://doi.org/10.1007/s11101-016-9470-4
  17. Tursun, X., Zhao, Y., Alat, Z., Xin, X., Tursun, A., Abdulla, R. and AkberAisa, H. 2016. Anti-inflammatory effect of Rosa rugosa flower extract in lipopolysaccharide-stimulated RAW 264.7 macrophages. Biomole. Ther. (Seoul) 24, 184-191. https://doi.org/10.4062/biomolther.2015.090
  18. Vezza, T., Rodriguez-Nogales, A., Algieri, F., Utrilla, M. P., Rodriguez-Cabezas, M. E. and Galvez, J. 2016. Flavonoids in inflammatory bowel disease: a review. Nutrients 8, 211. https://doi.org/10.3390/nu8040211
  19. Wang, X., Hu, D., Zhang, L., Lian, G., Zhao, S., Wang, C., Yin, J., Wu, C. and Yang, J. 2014. Gomisin A inhibits lipopolysaccharide- induced inflammatory responses in N9 microglia via blocking the NF-kappaB/MAPKs pathway. Food Chem. Toxicol. 63, 119-127. https://doi.org/10.1016/j.fct.2013.10.048
  20. World Health Organization. 2007. WHO monographs on selected medicinal plants, vol 3. Fructus Schisandrae. Geneva, 296-313.
  21. Yeo, M., Suhr, Y. J. and Ham, K. B. 2006. Crossroad between inflammation and carcinogenesis in colon. Kor. J. Med. 70, 130-137.