Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibitory effect of Petalonia binghamiae on neuroinflammation in LPS-stimulated microglial cells

LPS에 의해 활성화된 미세아교세포에서 미역쇠 추출물의 신경염증 보호 효과

  • Received : 2016.12.08
  • Accepted : 2017.01.18
  • Published : 2017.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.

퇴행성 뇌신경 질환의 원인이 되는 것으로 알려진 미세아교세포의 과도한 활성화에 의한 신경염증반응에 미치는 미역쇠의 보호 효과를 알아보기 위해 LPS를 처리한 BV2 세포에서 미역쇠에서 얻은 에탄올 추출물을 이용하여 실험을 수행하였다. 미세아교세포의 활성화를 유도하는 LPS의 처리는 신경염증반응의 지표인 NO의 생성량과 이들을 조절하는 iNOS, COX-2의 발현을 증가시켰다. 미역쇠 추출물의 처리는 LPS가 유도하는 NO의 생성량을 농도 의존적으로 억제하였고 iNOS와 COX-2의 발현을 억제하여 NO 생성량 저해와 유사한 양상의 결과를 나타내었다. 미역쇠 추출물의 신경 염증반응 저해 효과가 $NF-{\kappa}B$의 활성화 조절을 통해 일어나는지를 알아보기 위해 $NF-{\kappa}B$의 핵으로의 전이, $I{\kappa}B$의 인산화, $NF-{\kappa}B$ 억제제인 PDTC를 이용한 NO의 생성량에 미치는 효과를 확인하였다. 미역쇠 추출물 처리에 의해 핵분획물에서의 $NF-{\kappa}B$ 발현은 현저히 감소하였고 $I{\kappa}B$의 인산화를 억제하였으며 PDTC의 처리로 NO의 생성량은 감소하였다. 이상의 결과는 미세아교세포의 활성화로 인해 발생되는 신경염증반응에 미역쇠 추출물이 $NF-{\kappa}B$의 활성 억제를 통해 NO의 생성을 저해함으로써 항신경염증 효과가 있음을 보여주는 것으로 미역쇠 추출물이 신경염증 관련 뇌신경 질환의 제어하는데 있어서 치료효과를 가지는 소재로서 이용 가능성에 대한 정보를 제공할 것으로 사료된다.

Keywords

References

  1. Nakagawa Y, Chiba K. Role of microglial m1/m2 polarization in relapse and remission of psychiatric disorders and diseases. Pharmaceuticals (Basel) 2014; 7(12): 1028-1048. https://doi.org/10.3390/ph7121028
  2. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol 2010; 87(5): 779-789. https://doi.org/10.1189/jlb.1109766
  3. Griffin WS. Inflammation and neurodegenerative diseases. Am J Clin Nutr 2006; 83(2): 470S-474S. https://doi.org/10.1093/ajcn/83.2.470S
  4. Chung YC, Ko HW, Bok E, Park ES, Huh SH, Nam JH, Jin BK. The role of neuroinflammation on the pathogenesis of Parkinson's disease. BMB Rep 2010; 43(4): 225-232. https://doi.org/10.5483/BMBRep.2010.43.4.225
  5. Gonzalez H, Elgueta D, Montoya A, Pacheco R. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J Neuroimmunol 2014; 274(1-2): 1-13. https://doi.org/10.1016/j.jneuroim.2014.07.012
  6. Whitney NP, Eidem TM, Peng H, Huang Y, Zheng JC. Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders. J Neurochem 2009; 108(6): 1343-1359. https://doi.org/10.1111/j.1471-4159.2009.05886.x
  7. Yoon CH, Kim DC, KO WM, Kim KS, Lee DS, Kim DS, Cho HK, Seo J, Kim SY, Oh H, Kim YC. Anti-neuroinflammatory effects of Quercetin-3-O-glucuronide isolated from the leaf of Vitis labruscana on LPS-induced neuroinflammation in BV2 cells. Korean J Pharmacogn 2014; 45(1): 17-22.
  8. Dilshara MG, Jayasooriya RG, Lee S, Choi YH, Kim GY. Morin downregulates nitric oxide and prostaglandin E2 production in LPS-stimulated BV2 microglial cells by suppressing $NF-{\kappa}B$ activity and activating HO-1 induction. Environ Toxicol Pharmacol 2016; 44: 62-68. https://doi.org/10.1016/j.etap.2016.04.010
  9. Park E, Chun HS. Green tea polyphenol Epigallocatechine gallate (EGCG) prevented LPS-induced BV-2 micoglial cell activation. J Life Sci 2016; 26(6): 640-645. https://doi.org/10.5352/JLS.2016.26.6.640
  10. Min JS, Lee DS. A screen for dual-protection molecules from a natural product library against neuronal cell death and microglial cell activation. J Life Sci 2015; 25(6): 656-662. https://doi.org/10.5352/JLS.2015.25.6.656
  11. Galea E, Reis DJ, Fox ES, Xu H, Feinstein DL. CD14 mediate endotoxin induction of nitric oxide synthase in cultured brain glial cells. J Neuroimmunol 1996; 64(1): 19-28. https://doi.org/10.1016/0165-5728(95)00143-3
  12. Laflamme N, Rivest S. Toll-like receptor 4: the missing link of the cerebral innate immune response triggered by circulating gramnegative bacterial cell wall components. FASEB J 2001; 15(1): 155-163. https://doi.org/10.1096/fj.00-0339com
  13. Colton CA. Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 2009; 4(4): 399-418. https://doi.org/10.1007/s11481-009-9164-4
  14. Lee YP, Kang SY. A catalogue of the seaweeds in Korea. Jeju: Jeju National University Press; 2002.
  15. Noda H, Amano H, Arashima K, Hashimoto S, Nisizawa K. Studies on the antitumour activity of marine algae. Bull Jpn Soc Sci Fish 1989; 55(7): 1259-1264. https://doi.org/10.2331/suisan.55.1259
  16. Schwartsmann G, Brondani da Rocha A, Berlinck RG, Jimeno J. Marine organisms as a source of new anticancer agents. Lancet Oncol 2001; 2(4): 221-225. https://doi.org/10.1016/S1470-2045(00)00292-8
  17. Shin DB, Han EH, Park SS. Cytoprotective effects of Phaeophyta extracts from the coast of Jeju island in HT-22 mouse neuronal cells. J Korean Soc Food Sci Nutr 2014; 43(2): 224-230. https://doi.org/10.3746/jkfn.2014.43.2.224
  18. Athukorala Y, Kim KN, Jeon YJ. Antiproliferative and antioxidant properties of an enzymatic hydrolysate from brown alga, Ecklonia cava. Food Chem Toxicol 2006; 44(7): 1065-1074. https://doi.org/10.1016/j.fct.2006.01.011
  19. Ryu G, Park SH, Kim ES, Choi BW, Ryu SY, Lee BH. Cholinesterase inhibitory activity of two farnesylacetone derivatives from the brown alga Sargassum sagamianum. Arch Pharm Res 2003; 26(10): 796-799. https://doi.org/10.1007/BF02980022
  20. Park JC, Choi JS, Song SH, Choi MR, Kim KY, Choi JW. Hepatoprotective effect of extracts and phenolic compound from marine algae in bromobenzene-treated rats. Korean J Pharmacogn 1997; 28(4): 239-246.
  21. Park KE, Jang MS, Lim CW, Kim YK, Seo Y, Park HY. Antioxidant activity on ethanol extract from boiled-water of Hizikia fusiformis. J Korean Soc Appl Biol Chem 2005; 48(4): 435-439.
  22. Kang SI, Kim MH, Shin HS, Kim HM, Hong YS, Park JG, Ko HC, Lee NH, Chung WS, Kim SJ. A water-soluble extract of Petalonia binghamiae inhibits the expression of adipogenic regulators in 3T3-L1 preadipocytes and reduces adiposity and weight gain in rats fed a high-fat diet. J Nutr Biochem 2010; 21(12): 1251-1257. https://doi.org/10.1016/j.jnutbio.2009.11.008
  23. Kang SI, Jin YJ, Ko HC, Choi SY, Hwang JH, Whang I, Kim MH, Shin HS, Jeong HB, Kim SJ. Petalonia improves glucose homeostasis in streptozotocin-induced diabetic mice. Biochem Biophys Res Commun 2008; 373(2): 265-269. https://doi.org/10.1016/j.bbrc.2008.06.015
  24. Yoon HS, Koh WB, Oh YS, Kim IJ. The Anti-melanogenic effects of Petalonia binghamiae extracts in $\alpha$-melanocyte stimulating hormone-induced B16/F10 murine melanoma cells. J Korean Soc Appl Biol Chem 2009; 52(5): 564-567. https://doi.org/10.3839/jksabc.2009.095
  25. Lee SG, Kim MM. Anti-inflammatory effect of scopoletin in RAW264.7 macrophages. J Life Sci 2015; 25(12): 1377-1383. https://doi.org/10.5352/JLS.2015.25.12.1377
  26. Jiang Z, Li C, Arrick DM, Yang S, Baluna AE, Sun H. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia. PLoS One 2014; 9(3): e93134. https://doi.org/10.1371/journal.pone.0093134
  27. Wang JY, Lee CT, Wang JY. Nitric oxide plays a dual role in the oxidative injury of cultured rat microglia but not astroglia. Neuroscience 2014; 281: 164-177. https://doi.org/10.1016/j.neuroscience.2014.09.048
  28. Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P. Interleukin-1 beta and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci Lett 1995; 202(1-2): 17-20. https://doi.org/10.1016/0304-3940(95)12192-7
  29. Li M, Dai FR, Du XP, Yang QD, Chen Y. Neuroprotection by silencing iNOS expression in a 6-OHDA model of Parkinson's disease. J Mol Neurosci 2012; 48(1): 225-233. https://doi.org/10.1007/s12031-012-9814-5
  30. Gulati P, Singh N. Pharmacological evidence for connection of nitric oxide-mediated pathways in neuroprotective mechanism of ischemic postconditioning in mice. J Pharm Bioallied Sci 2014; 6(4): 233-240. https://doi.org/10.4103/0975-7406.142951
  31. Okamoto S, Lipton SA. S-nitrosylation in neurogenesis and neuronal development. Biochim Biophys Acta 2015; 1850(8): 1588-1593. https://doi.org/10.1016/j.bbagen.2014.12.013
  32. Verstrepen L, Beyaert R. Receptor proximal kinases in $NF-{\kappa}B$ signaling as potential therapeutic targets in cancer and inflammation. Biochem Pharmacol 2014; 92(4): 519-529. https://doi.org/10.1016/j.bcp.2014.10.017
  33. Carmody RJ, Chen YH. Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. Cell Mol Immunol 2007; 4(1): 31-41.
  34. Hatziieremia S, Gray AI, Ferro VA, Paul A, Plevin R. The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and MAP kinase and NFkappaB signalling pathways in monocytes/macrophages. Br J Pharmacol 2006; 149(2): 188-198. https://doi.org/10.1038/sj.bjp.0706856
  35. Gasparini C, Feldmann M. $NF-{\kappa}B$ as a target for modulating inflammatory responses. Curr Pharm Des 2012; 18(35): 5735-5745. https://doi.org/10.2174/138161212803530763
  36. Zhou W, Hu W. Anti-neuroinflammatory agents for the treatment of Alzheimer's disease. Future Med Chem 2013; 5(13): 1559-1571. https://doi.org/10.4155/fmc.13.125
  37. Duarte J, Francisco V, Perez-Vizcaino F. Modulation of nitric oxide by flavonoids. Food Funct 2014; 5(8): 1653-1668. https://doi.org/10.1039/C4FO00144C

Cited by

  1. LPS에 의해 활성화된 미세아교세포에서 흰점박이꽃무지 에탄올 추출물의 신경염증 억제 효과 vol.29, pp.10, 2017, https://doi.org/10.5352/jls.2019.29.10.1096
  2. BV-2 미세아교세포에서 왕귀뚜라미 유래 Teleogryllusine의 신경염증 억제 효과 vol.30, pp.11, 2017, https://doi.org/10.5352/jls.2020.30.11.999