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섬괴불나무(Lonicera insularis Nakai) 추출물의 면역자극 및 항비만 활성

Immunostimulatory and Anti-Obesity Activity of Lonicera insularis Nakai Extracts in Mouse Macrophages RAW264.7 Cells and Mouse Adipocytes 3T3-L1 Cells

이재원|최민영|금나경|여주호|정진부|안미연|유주형
한국자원식물학회 (The Plant Resources Society Of Korea)|2022.08|한국자원식물학회지 (Korean Journal of Plant Reources.)|제35권 제4호|pp. 417-427

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키워드

3T3-L1MacrophagesLipolysisAdipocytesAnti-obesity activityDifferetitationImmuno-stimulatory activityLonicera Insularis Nakai

초록

본 연구에서는 섬괴불나무 열매(LIF), 잎(LIL) 그리고 줄기(LIS) 추출물의 면역증진 활성과 섬괴불나무 열매(LIF) 추출물의 항비만 활성을 평가하였다. 섬괴불나무 열매(LIF), 잎(LIL) 그리고 줄기(LIS) 추출물은 RAW264.7 세포에서 NO, iNOS, COX-2, IL-1β, TNF-α와 같은 면역증진인자의 생성을 증가시켰으며, IL-1β의 발현은 NO생성과 관련된 것으로 보여진다. 면역증진인자은 TLR2/4를 통해 MAPKs중 p38 그리고 JNK를 자극하여 발현이 유도되는 것으로 판단된다. 항비만 실험에서, 섬괴불나무 열매(LIF) 추출물은 AMPK, HSL, ATGL의 발현 증가와 perilipin-1 발현 억제를통해 지질분해를 유도하여 세포 내지질축적을 억제하는 것으로 나타났으며, 갈색지방세포로의분화유도와 에너지 대사에 관여하는 인자인 PRDM16, PGC-1 α의 발현유도를 통해서도 지질축적을 억제하는 것으로 판단된다. 향후 섬괴불나무 추출물은 건강 보조제 및 기능성 식품으로의 활용이 가능할 것으로 판단되지만, 섬괴물나무 추출물의 어떠한 성분이 면역과 항비만 활성에 영향을 미치는지에 대한 성분분석이 필요하다. 또한, 본 연구는 세포를 이용한 실험으로정확한 분석을 위해서는 동물모델을 이용한 섬괴불나무 추출물의 면역증진 및 항비만 활성에 관한 추가적인 연구가 진행되어야 할 것이다

Abstract

In this study, we investigated in vitro immuno-stimulatory and anti-obesity activity of fruit (LIF), leaves (LIL) and stems (LIS) from Lonicera insularis Nakai in mouse macrophages RAW264.7 cells and mouse pre-adipocytes 3T3-L1 cells. LIF, LIL and LIS increased the production of immunostimulatory factors such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and activated phagocytosis in RAW264.7 cells. Inhibition of toll-like receptor 2/4 (TLR2/4) partly blocked LIF, LIL and LIS mediated production of immunostimulatory factors. In addition, inhibition of mitogen-activated protein kinases (MAPK) signaling attenuated the production of immunostimulatory factors induced by LIF, LIL and LIS. Based on these results of this study, LIF, LIL and LIS is thought to activate macrophages the production of immunostimulatory factors and phagocytosis through toll-like receptor 2/4 (TLR2/4) and MAPKs signaling pathway. In anti-obesity study, LIF reduced the lipid accumulation in 3T3-L1 cells. LIF increased the protein phosphorylation expressions such as AMP-activated protein kinase (AMPK), hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL) related to the lipolysis of the adipocytes. In addition, LIF increased the expression of proteins involved in energy metabolism and brown adipose tissues differentiation such as peroxisome proliferator-activated receptor gamma coativator 1α (PGC-1α) and PR domain-containing16 (PRDM16). These results suggest that LIF is involved in lipid accumulation inhibition through expressing the proteins such as lipolysis and differentiation of white adipocytes to brown adipocytes.

참고문헌 (47)

  1. Ahmadian, M., "Lipolysis in adipocytes", Int. J. Biochem. Cell Biol, 42(5), pp.555~559 (2010)
  2. Alam, M. B., "Antimelanogenic activities of Heracleum moellendorffii via ERK1", 2-mediated MITF downregulation, 2016, pp.17(11), 1844~
  3. Alam, R., "Mitogen-activated protein kinase signalling and ERK1", 2 bistability in asthma, 2011, pp.41(2), 149~159
  4. Bai, Y., "Xinjiang herbal tea exerts immunomodulatory activity via TLR2", 4-mediated MAPK signaling pathways in RAW264. 7 cells and prevents cyclophosphamide-induced immunosuppression in mice, 2019, pp.228, 179~187
  5. Bandaru, P., "The impact of obesity on immune response to infection and vaccine : an insight into plausible mechanisms", Endocrinol. Metab. Synd, 2, pp.2~ (2013)
  6. Barr, R. K., "The c-Jun N-terminal protein kinase family of mitogen-activated protein kinases(JNK MAPKs)", Int J. Biochem. Cell Biol, 33(11), pp.1047~1063 (2001)
  7. Bogdan, C., "Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity", Curr. Opin. Immunol, 12(1), pp.64~76 (2000)
  8. Calder, P. C, "Nutrition, immunity and COVID-19", J. Nutr. Health, 3(1), pp.74~ (2020)
  9. Cavaillon, J. M, "Cytokines and macrophages", Biomed. Pharmacother, 48(10), pp.445~453 (1994)
  10. Cuadrado, A., "Mechanisms and functions of p38 MAPK signalling", Biochem. J, 429(3), pp.403~417 (2010)
  11. Cuthbertson, D. J., "COVID-19 and obesity : an opportunity for change", Ther. Adv. Endocrinol. Metab, 11, pp.1~4 (2020)
  12. De Heredia, F. P., "Obesity, inflammation and the immune system", Proc. Nutr. Soc, 71(2), pp.332~338 (2012)
  13. De Oliviera Nascimento, L., "The role of TLR2 in infection and immunity", Front. Immunol, 3, pp.79~ (2012)
  14. Gammone, M. A., "Anti-obesity activity of the marine carotenoid fucoxanthin", Mar. Drugs, 13(4), pp.2196~2214 (2015)
  15. Giroux, M., "Cyclooxygenase-2 expression in macrophages : modulation by protein kinase C-α", J. Immunol, 165(7), pp.3985~3991 (2000)
  16. Goodwin, J. S., "Regulation of the immune response by prostaglandins", Clin. Immunol. Immunopathol, 15(1), pp.106~122 (1980)
  17. Guo, Y. J., "ERK", MAPK signalling pathway and tumorigenesis, 2020, pp.19(3), 1997~2007
  18. Hansen, J. S., "Visualization of lipid directed dynamics of perilipin 1 in human primary adipocytes", Sci. Rep, 7(1), pp.1~14 (2017)
  19. Hirayama, D., "The phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis", Int. J. Mol. Sci, 19(1), pp.92~ (2018)
  20. Hussain, A., "Obesity and mortality of COVID-19. Meta-analysis", Obes. Res. Clin. Pract, 14(4), pp.295~300 (2020)
  21. Hwang, J. T., "Anti-obesity effects of ginsenoside Rh2 are associated with the activation of AMPK signaling pathway in 3T3-L1 adipocyte", Biochem. Biophys. Res. Commun, 364(4), pp.1002~1008 (2007)
  22. 정금선, "엽록체 DNA를 이용한 섬괴불나무(Lonicera insularis Nakai)의 종내변이 및 지리학적 연구", 식물분류학회지, 44(3), pp.202~207 (2014), 한국식물분류학회
  23. Johan, W. E., "Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state", J. Clin. Endocrinol. Metab, 92(6), pp.2292~2299 (2007)
  24. Kim, M. S, "Chemical Constituents from Lonicera insularis", MS, pp.2017
  25. Lake, D., "Negative feedback regulation of the ERK1", 2 MAPK pathway, 2016, pp.73(23), 4397~4413
  26. 이은호, "울릉도 자생식물인 섬괴불나무(Lonicera morrowii A.Gray) 잎 추출물의 생리활성", Journal of Applied Biological Chemistry, 63(4), pp.443~449 (2020), 한국응용생명화학회
  27. Lee, J. S., "Immunostimulating activity of the polysaccharides isolated from Cordyceps militaris", Int. Immunopharmacol, 11(9), pp.1226~1233 (2011)
  28. Lima-Junior, D. S., "Inflammasome-derived IL-1β production induces nitric oxide–mediated resistance to Leishmania", Nat. Med, 19(7), pp.909~915 (2013)
  29. Marcato, L. G., "The role of Toll-like receptors 2 and 4 on reactive oxygen species and nitric oxide production by macrophage cells stimulated with root canal pathogens", Oral Microbiol. Immunol, 23(5), pp.353~359 (2008)
  30. McNeill, E., "Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation", Free Radic. Biol. Med, 79, pp.206~216 (2015)
  31. Mihaylova, M. M., "The AMPK signalling pathway coordinates cell growth, autophagy and metabolism", Nat. Rev. Mol. Cell Biol, 13(9), pp.1016~1023 (2011)
  32. Mukherjee, S., "TLR2 and TLR4 mediated host immune responses in major infectious diseases : a review", Braz. J. Infect. Dis, 20, pp.193~204 (2016)
  33. Pettersson-Klein, A. T., "Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration", Mol. Metab, 9, pp.28~42 (2018)
  34. Ren, D., "Chemical characterization of a novel polysaccharide ASKP-1 from Artemisia sphaerocephala Krasch seed and its macrophage activation via MAPK, PI3k", Akt and NF-κB signaling pathways in RAW264. 7 cells, 2017, pp.8(3), 1299~1312
  35. Seale, P., "PRDM16 controls a brown fat", skeletal muscle switch, 2008, pp.454(7207), 961~967
  36. Suzanne, S. M., "Causes of obesity", Abdom. Radiol, 37(5), pp.730~732 (2012)
  37. Takeda, K., "TLR signaling pathways", Semin. Immunol, 16(1), pp.3~9 (2004)
  38. Wang, J., "Novel anti-obesity peptide(RLLPH)derived from hazelnut(Corylus heterophylla Fisch)protein hydrolysates inhibits adipogenesis in 3T3-L1 adipocytes by regulating adipogenic transcription factors and adenosine monophosphate-activated protein kinase(AMPK)activation", J. Biosci. Bioeng, 129(3), pp.259~268 (2020)
  39. Wang, T., "TNF-α and IL-6 : The link between immune and bone system", Curr. Drug Targets, 21(3), pp.213~227 (2020)
  40. Weber, A., "Interleukin-1β(IL-1β)processing pathway", Sci. Signal, 3(105), pp.2~ (2010)
  41. Wronska, A., "Structural and biochemical characteristics of various white adipose tissue depots", Acta. Physiol, 205(2), pp.194~208 (2012)
  42. Yang, F., "A polysaccharide isolated from the fruits of Physalis alkekengi L. induces RAW264. 7 macrophages activation via TLR2 and TLR4-mediated MAPK and NF-κB signaling pathways", Int. J. Biol. Macromol, 140, pp.895~906 (2019)[DOI]
  43. Yang, Y., "Immunostimulatory effects of sulfated chitosans on RAW 264.7 mouse macrophages via the activation of PI3K", Akt signaling pathway, 2018, pp.108, 1310~1321
  44. Yokokawa, T., "Dehydroepiandrosterone activates AMP kinase and regulates GLUT4 and PGC-1α expression in C2C12 myotubes", Biochem. Biophys. Res. Commun, 463(1-2), pp.42~47 (2015)[DOI]
  45. Yoneshiro, T., "Activation and recruitment of brown adipose tissue as anti-obesity regimens in humans", Ann. Intern. Med, 47(2), pp.133~141 (2015)
  46. Yoshizumi, M., "Src and Cas mediate JNK activation but not ERK1", 2 and p38 kinases by reactive oxygen species, 2000, pp.275(16), 11706~11712
  47. 유주형, "금화규(Abelmoschus manihot) 뿌리 추출물의 면역증진 및 항비만효과", 한국자원식물학회지, 34(5), pp.411~419 (2021), 한국자원식물학회

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