DOI QR코드

DOI QR Code

Anti-inflammatory effect of beluga lentil extract in RAW 264.7 macrophages

RAW 264.7 대식세포에서 벨루가 렌틸 추출물의 항염증 효과

  • Hyeon-Ji Song (Department of Food Science and Technology, Keimyung University) ;
  • Syng-Ook Lee (Department of Food Science and Technology, Keimyung University)
  • 송현지 (계명대학교 식품가공학과) ;
  • 이승욱 (계명대학교 식품가공학과)
  • Received : 2024.04.18
  • Accepted : 2024.05.13
  • Published : 2024.06.30

Abstract

The anti-inflammatory effect of beluga lentil extract (BLE) and its underlying mechanisms were investigated in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Treatment with BLE significantly decreased nitric oxide (NO) production and protein and mRNA expressions of inducible NO synthase (iNOS) in LPS-treated RAW 264.7 cells. Down-regulation of this inflammatory gene expression was not associated with NF-κB/MAPK signaling pathways, and further mechanistic studies demonstrated that BLE decreased LPS-induced iNOS expression through upregulation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated heme oxygenase-1 (HO-1) expression. These results suggest that beluga lentil represent a potential source of natural anti-inflammatory agents, and further studies will be necessary to determine its anti-inflammatory effects in vivo.

본 연구에서는 벨루가 렌틸 추출물(BLE)의 항염증 효능을 NO 생성 측면에서 검토하고 이와 관련된 분자 기전을 규명하고자 하였다. LPS, LTA 및 지방세포 공동배양에 의해 활성화된 RAW 264.7 대식세포에서 BLE는 독성이 없는 농도 범위에서 유의적인 NO 생성 저해 효과를 보였다. 이와 함께 BLE 처리에 따라 iNOS mRNA 및 단백질의 발현이 유의적으로 저해됨을 확인하였으며, 이는 BLE에 의한 NO 생성 억제 효과가 전사 수준에서의 iNOS 발현을 억제함으로부터 기인하는 것임을 시사한다. 추가적으로 BLE는 NO 외에도 활성화된 대식세포에서 증가하는 다양한 염증성 사이토카인 유전자(COX-2, IL-1β 및 IL-6)의 mRNA 발현 또한 유의적으로 억제하는 것으로 나타났다. BLE의 항염증 효과와 관련된 분자 기전에 관한 추가적인 연구를 수행한 결과, 항염증 관련 대표 기전인 NF-κB/MAP kinases 신호 경로와는 연관성이 없는 것으로 나타났다. 반면, BLE 처리에 따라 Nrf2 단백질 발현의 증가 및 활성화가 유도되고 HO-1의 발현이 유의적으로 증가하는 것을 확인함으로써 Nrf2가 HO-1의 발현을 증가시키기 위한 전사 인자로서 작용할 가능성이 높음을 확인하였다. 따라서, 본 연구를 통해 식용원료 유래의 잠재적인 항염증 소재로서 BLE의 활용 가능성을 확인할 수 있었으며, 향후 동물모델을 대상으로 항염증 효과를 입증하기 위한 추가적인 연구가 필요할 것으로 생각된다.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea [NRF-2023R1A2C1003582].

References

  1. Agil R, Gaget A, Gliwa J, Avis TJ, Willmore WG, Hosseinian F. Lentils enhance probiotic growth in yogurt and provide added benefit of antioxidant protection. Food Sci Technol, 50, 45-49 (2013)
  2. Cerella C, Sobolewski C, Dicato M, Diederich M. Targeting COX-2 expression by natural compounds: A promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy. Biochem Pharmacol, 80, 1801-1815 (2010)
  3. Chawla A, Nguyen KD, Goh YPS. Macrophage-mediated inflammation in metabolic disease. Nat Rev Immunol, 11, 738-749 (2011)
  4. Gramlich T, Petras RE. Pathology of inflammatory bowel disease. Semin Pediatr Surg, 16, 154-163 (2007)
  5. Guo LY, Hung TM, Bae KH, Shin EM, Zhou HY, Hong YN, et al. Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. Eur J Pharmacol, 591, 293-299 (2008)
  6. Hink U, Munzel T. COX-2, another important player in the nitric oxide-endothelin cross-talk: Good news for COX-2 inhibitors?. Circ Res, 98, 1344-1346 (2006)
  7. Jang HY, Lee SO. Heme oxygenase 1-mediated anti-inflammatory effect of extract from the aerial part of Heracleum moellendorffii Hance. Foods, 12, 3309 (2023)
  8. Johnson CR, Thavarajah D, Combs Jr GF, Thavarajah P. Lentil (Lens culinaris L.): A prebiotic-rich whole food legume. Food Res Int, 51, 107-113 (2013)
  9. Johnson G, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 298, 1911-1912 (2002)
  10. Jung YS, Lee SH, Chun SY, Kim DH, Jang BI, Han MH, Lee SO. In vitro and in vivo protective effects of lentil (Lens culinaris) extract against oxidative stress-induced hepatotoxicity. Molecules, 27, 59 (2022)
  11. Kim SY, Kim BH. The anti-oxidative and anti-inflammatory effects of acai berry ethanol extracts using RAW 264.7 cells and TPA-induced mouse edema model. MS Thesis, Keimyung University, Korea, P 152 (2016)
  12. Kim YH, Park YH, Namkoon SG, Lee JS. Esculetin inhibits the inflammatory response by inducing heme oxygenase-1 in co-cultured macrophages and adipocytes. Food Funct, 5, 2371-2377 (2014)
  13. Kim YJ, Son DY. Inflammatory mediator regulation of the Zizyphus jujube leaf fractions in the LPS-stimulated RAW 264.7 mouse macrophage. Korean J Food Preserv, 21, 114-120 (2014)
  14. Kim YS, Lee SJ, Hwang JW, Kim EH, Park PJ, Jeong JH. Anti-inflammatory effects of extracts from Ligustrum ovalifolium H. leaves on RAW 264.7 macrophages. J Korean Soc Food Sci Nutr, 41, 1205-1210 (2012)
  15. Lee JH. Anti-inflammatory effects of ethanolic extracts from native Chinese plants. MS Thesis, Keimyung University, Korea, P 8-14 (2017)
  16. Lee JY, Joo DH, Yoo DH, Chae JW. Anti-inflammatory activities verification of Vaccinum oldhamifruit ethanol extracts on RAW 264.7. J Life Sci, 27, 417-422 (2017)
  17. Lee SH, Lee SO. Polyphenol contents and antioxidant activities of lentil extracts from different cultivars. J Korean Soc Food Sci Nutr, 45, 973-979 (2016)
  18. Lee TH, Kwak HB, Kim HH, Lee ZH, Chung DK, Baek NI, Kim J. Methanol extracts of Stewartia koreana inhibit cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) gene expression by blocking NF-κB transactivation in LPS-activated RAW 264.7 cells. Mol Cells, 23, 398-404 (2007)
  19. Ryter SW. Heme oxygenase-1: An anti-Inflammatory effector in cardiovascular, lung, and related metabolic disorders. Antioxidants, 11, 555 (2022)
  20. Seo MK, Chu HN, Lee DB, Kim HR, Hwang IS, Jeong YJ, Yoon SR, Kang SS, Jang KA, Kang MS. Ethanol extract of Aster glehni exhibits anti- inflammatory and anti-oxidant effects in RAW 264.7 cells and Caenorhabditis elegans. Korean J Food Preserv, 30, 1095-1106 (2023)
  21. Sung JM. Research trend and characteristic of imported functional grains. Korean J Food Sci Technol, 48, 35-41 (2015)
  22. Thavarajah D, Thavarajah P, Sarker A, Vandenberg A. Lentils (Lens culinaris Medikus subspecies culinaris): A whole food for increased iron and zinc intake. J Agric Food Chem, 57, 5413-5419 (2009)
  23. Van Q, Nayak BN, Reimer M, Jones PJ, Fulcher RG, Rempel CB. Anti-inflammatory effect of Inonotus obliquus, Polygala senega L. and Viburnum trilobum in a cell screening assay. J Ethnopharmacol, 125, 487-493 (2009)
  24. Woo HS, Lee SM, Heo JD, Lee MS, Kim YS, Kim DW. Anti-inflammatory activity of extracts of Hovenia dulcis on lipopolysaccharides-stimulated RAW 264.7 cells. Korean J Plant Res, 31, 466-477 (2018)
  25. Yun KJ, Kim JY, Kim JB, Lee KW, Jeong SY, Park HJ, et al. Inhibition of LPS-induced NO and PGE2 production by asiatic acid via NF-kappa B inactivation in RAW 264.7 macrophages: Possible involvement of the IKK and MAPK pathways. Int Immunopharmacol, 8, 431-441 (2008)
  26. Zang B, Deng Z, Ramdath DD, Tang Y, Chen PX, Liu R, Liu Q, Tsao R. Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipase. Food Chem, 172, 862-872 (2015)