DOI QR코드

DOI QR Code

Protective Effect of Protocatechuic Acid, Phenolic Compound of Momordica Charantia, against Oxidative Stress and Neuroinflammation in C6 Glial Cell

여주의 페놀성 화합물인 Protocatechuic Acid의 산화적 스트레스 개선 및 신경염증 보호 효과

  • Kim, Ji-Hyun (Department of Food Science and Nutrition, Pusan National University) ;
  • Choi, Jung Ran (Department of Food Science and Nutrition, Pusan National University) ;
  • Cho, Eun Ju (Department of Food Science and Nutrition, Pusan National University) ;
  • Kim, Hyun Young (Department of Food Science, Gyeongnam National University of Science and Technology)
  • 김지현 (부산대학교 식품영양학과) ;
  • 최정란 (부산대학교 식품영양학과) ;
  • 조은주 (부산대학교 식품영양학과) ;
  • 김현영 (경남과학기술대학교 식품과학부)
  • Received : 2020.05.05
  • Accepted : 2020.06.10
  • Published : 2020.06.30

Abstract

Objectives: Oxidative stress-mediated neuroinflammation has been supposed as a crucial factor that contributes to the pathogenesis of many neurodegenerative diseases. In this study, we aimed to investigate the protective activity against oxidative stress and neuroinflammation of protocatechuic acid (PA), active phenolic compound from Momordica Charantia. Methods: Protective activity of PA from oxidative stress was performed under in vitro conditions. Our study investigated the protective mechanism of PA from neuroinflammation in cellular system using C6 glial cell. To investigate the improvement the effects on oxidative stress and neuroinflammation, we induced oxidative stress by H2O2 (100 μM) stimulation and induced neuroinflammation by treatment with lipopolysaccharide (LPS) (1 ㎍/mL) and interferon-gamma (IFN-γ) (10 ng/mL) in C6 glial cells. Results: PA showed strong radical scavenging effect against 1,1-dipenyl-2-picrylhydrazyl, hydroxy radical (·OH) and nitric oxide (NO). Under oxidative stress treated by H2O2, the result showed the increased mRNA expressions of oxidative stress markers such as nuclear factor-kappaB (NF-κB), cyclooxygenase (COX-2) and inducible nitric oxide (iNOS). However, the treatment of PA led to reduced mRNA expressions of NF-κB, COX-2 and iNOS. Moreover, PA attenuated the production of interleukin-6 and scavenged NO generated by both endotoxin LPS and IFN-γ together. Furthermore, it also reduced LPS and IFN-γ-induced mRNA expressions of iNOS and COX-2. Conclusions: In conclusion, our results collectively suggest that PA, phenolic compound of Momordica Charantia, could be a safe anti-oxidant and a promising anti-neuroinflammatory molecule for neurodegenerative diseases.

Keywords

References

  1. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radical and antioxidants in normal physiological function and human disease. Int J Biochem Cell Biol. 2007 ; 39(1) : 44-84. https://doi.org/10.1016/j.biocel.2006.07.001
  2. Kang SJ, Park WC, Kim TS. Changes in antioxidant and antioxidant enzymes activities of soybean leaves subjected to water stress. J Korean Soc Appl Bi. 1999 ; 42(3): 246-51.
  3. Kumar R, Balaji S, Sripriya R, Nithya N, Uma TS, Sehgal PK. In vitro evaluation of antioxidants of fruit extract of Momordica charantia L. on fibroblasts and keratinocytes. J Agric Food Chem. 2010 ; 58(3) : 1518-22. https://doi.org/10.1021/jf9025986
  4. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993 ; 362(6415) : 59-62. https://doi.org/10.1038/362059a0
  5. Reynolds A, Laurie C, Mosley RL, Gendelman HE. Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol. 2007 ; 82 : 297-325. https://doi.org/10.1016/S0074-7742(07)82016-2
  6. Knott AB, Perkins G, Schwarzenbacher R, Bossy-Wetzel E Mitochondrial fragmentation in neurodegeneration. Nat Rev Neurosci. 2008 ; 9(7) : 505-18. https://doi.org/10.1038/nrn2417
  7. Han IO, Kim KW, Ryu JH, Kim WK. p38 mitogen- activated protein kinase mediates lipopolysaccharide, not interferon-${\gamma}$, -induced inducible nitric oxide synthase expression in mouse BV2 microglial cells. Neurosci Lett. 2002 ; 325(1) : 9-12. https://doi.org/10.1016/S0304-3940(02)00218-5
  8. Pillot T, Drouet B, Queille S, Labeur C, Vandekerchkhove J, Rosseneu M, et al. The nonfibrillar amyloid ${\beta}$-peptide induces apoptotic neuronal cell death. J Neurochem. 1999 ; 73(4) : 1626-34. https://doi.org/10.1046/j.1471-4159.1999.0731626.x
  9. Grover JK, Yadav S, Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol. 2002 ; 81(1) : 81-100. https://doi.org/10.1016/S0378-8741(02)00059-4
  10. Lee HJ, Moon JH, Lee WM, Lee SG, Kim AK, Woo YH, et al. Charantin contents and fruit characteristics of bitter gourd (Momordica charantia L.) accessions. J Bio-Env Con. 2012 ; 21(4) : 379-84. https://doi.org/10.12791/KSBEC.2012.21.4.379
  11. Choi JS, Kim HY, Seo WT, Lee JH, Cho KM. Roasting enhances antioxidant effect of bitter melon (Momordica charantia L.) increasing in flavan-3-ol and phenolic acid contents. Food Sci Biotechnol. 2012 ; 21(1) : 19-26. https://doi.org/10.1007/s10068-012-0003-7
  12. Zhang Q, Mejia EG. Protocatechuic acid attenuates adipogenesis-induced inflammation and mitochondrial dysfunction in 3T3-L1 adipocytes by regulation of AMPK pathway. J Funct Foods. 2020 ; 69 : 103972. https://doi.org/10.1016/j.jff.2020.103972
  13. Akanni OO, Owumi SE, Olowofela OG, Adeyanju AA, Abiola OJ, Adaramoye OA. Protocatechuic acid ameliorates testosterone-induced benign prostatic hyperplasia through the regulation of inflammation and oxidative stress in castrated rats. J Biochem Mol Toxicol. 2020 ; e22502. https://doi.org/10.1002/jbt.22502
  14. An LJ, Guan S, Shi GF, Bao YM, Duan YL, Jiang B. Protocatechuic acid from Alpinia oxyphylla against MPP+-induced neurotoxicity in PC12 cells. Food Chem Toxicol. 2006 ; 44 : 436-43. https://doi.org/10.1016/j.fct.2005.08.017
  15. Ban JY, Cho SO, Jeon S-Y, Bae K, Song K-S, Seong YH. 3,4-Dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid ${\beta}$ protein (25-35)-induced neurotoxicity in cultured rat cortical neurons. Neurosci Lett. 2007 ; 420 : 184-8. https://doi.org/10.1016/j.neulet.2007.05.009
  16. Kim KB, Lee S, Heo JH, Kim JH. Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells. J Nutr Health. 2017 ; 50(5) : 415-25. https://doi.org/10.4163/jnh.2017.50.5.415
  17. Sofroniew MV, Vinters HV. Astrocytes: biology and pathology. Acta Neuropathol. 2010 ; 119(1) : 7-35. https://doi.org/10.1007/s00401-009-0619-8
  18. O'Brien ER, Howarth C, Sibson NR. The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches. Front Cell Neurosci. 2013 ; 7 : 40. https://doi.org/10.3389/fncel.2013.00040
  19. Falsig J, Latta M, Leist M. Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95- driven apoptosis. J Neurochem. 2004 ; 88(1) : 181-93. https://doi.org/10.1111/j.1471-4159.2004.02144.x
  20. Swanson RA, Ying W, Kauppinen TM. Astrocyte influences on ischemic neuronal death. Curr Mol Med. 2004 ; 4(2) : 193-205. https://doi.org/10.2174/1566524043479185
  21. Choi JR, Choi JM, Lee S, Cho KM, Cho EJ, Kim HY. The protective effects of protocatechuic acid from Momordica charantia against oxidative stress in neuronal cells. Kor J Pharmacogn. 2014 ; 45(1) : 11-6.
  22. Bi J, Jiang B, Zorn A, Zhao R-G, Liu P, An L-J. Catalpol inhibits LPS plus IFN-${\gamma}$-induced inflammatory response in astrocytes primary cultures. Toxicol In Vitro. 2013 ; 27(2) : 543-50. https://doi.org/10.1016/j.tiv.2012.09.023
  23. Hatano T, Edamatsu R, Hiramatsu M, Mori A, Fujita Y, Yasuhara T, et al. Effects of the interaction of tannins with co-existing substances. VI.: Effects of tannins and related polyphenols on superoxide anion radical, and on 1, 1-Diphenyl-2-picrylhydrazyl radical. Chem Pharm Bull. 1989 ; 37(8) : 2016-21. https://doi.org/10.1248/cpb.37.2016
  24. Chung SK, Osawa T, Kawakishi S. Hydroxyl radical-scavenging effects of spices and scavengers from brown mustard (Brassica nigra). Biosci Biotech Biochem. 1997 ; 61(1) : 118-23. https://doi.org/10.1271/bbb.61.118
  25. Marcocci L, Maguire JJ, Droy-Lefaix MT, Packer L. The nitric oxide-scavenging properties of ginkgo biloba extract EGb 761. Biochem Biophys Res Commun. 1994 ; 201(2) : 748-55. https://doi.org/10.1006/bbrc.1994.1764
  26. Hong J , Wie M, L eem D , Park KS, Yoon T, N o K-M, et al. Evaluation of antioxidants activity through the chemical assay. J Biomed Res. 2010 ; 11(1) : 1-8.
  27. Sakanaka S, Tachibana Y, Okada Y. Preparation and antioxidant properties of extracts of Japanese persimmon leaf tea (kakinoha-cha). Food Chem. 2005 ; 89 : 569-75. https://doi.org/10.1016/j.foodchem.2004.03.013
  28. Nakagawa T, Yokozawa T. Direct scavenging of nitric oxide and superoxide by green tea. Food Chem Toxicol. 2002 ; 40(12) : 1745-50. https://doi.org/10.1016/S0278-6915(02)00169-2
  29. Lee AY, Lee MH, Lee S, Cho EJ. Comparative study on antioxidant activity of vegetable oils under in vitro and cellular system. J Agric Sci. 2015 ; 7(3) : 58-65.
  30. McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson'S and Alzheimer's disease brains. Neurology. 1988 ; 38(8) : 1285-91. https://doi.org/10.1212/WNL.38.8.1285
  31. Furukawa Y, Hara R-I, Nakaya M, Okuyama S, Sawamoto A, Nakajima M. Citrus auraptene induces glial cell line-derived neurotrophic factor in C6 cells. Int J Mol Sci. 2019 ; 21(1) : 253. https://doi.org/10.3390/ijms21010253
  32. Gulcin I, Elmastas M, Aboul-Enein HY. Determination of antioxidant and radical scavenging activity of Basil (Ocimum basilicum L. Family Lamiaceae) assayed by different methodologies. Phytother Res. 2007 ; 21(4) : 354-61. https://doi.org/10.1002/ptr.2069
  33. Crack PJ, Taylor JM. Reactive oxygen species and the modulation of stroke. 2005. Free Radic Biol Med. 2005 ; 38(11) : 1433-44. https://doi.org/10.1016/j.freeradbiomed.2005.01.019
  34. Korhonen P, Helenius M, Salminen A. Age-related changes in the regulation of transcription factor $NF-{\kappa}B$ in rat brain. Neurosci Lett. 1997 ; 225(1) : 61-4. https://doi.org/10.1016/S0304-3940(97)00190-0
  35. Luo SF, Wang CC, Chien CS, Hsiao LD, Yang CM. Induction of cyclooxygenase-2 by lipopolysaccharide in canine tracheal smooth muscle cells: involvement of p42/p44 and p38 mitogen-activated protein kinases and nuclear $factor-{\kappa}B$ pathways. Cell Signal. 2003 ; 15(5) : 497-509. https://doi.org/10.1016/S0898-6568(02)00135-3
  36. Chung HY, Kim HJ, Jung KJ, Yoon JS, Yoo MA, Kim KW, et al. The inflammatory process in aging. Rev Clin Gerontol. 2000 ; 10(3) : 207-22. https://doi.org/10.1017/S0959259800010327
  37. Martel-Pelletier J, Pelletier JP, Fahmi H. Cyclooxygenase-2 and prostaglandins in articular tissues. Semin Arthritis Rheum. 2003 ; 33(3) : 155-67. https://doi.org/10.1016/S0049-0172(03)00134-3
  38. Mrak RE, Sheng JG, Griffin WS. Glial cytokines in Alzheimer's disease: Review and pathogenic implications. Hum Pathol. 1995 ; 26(8) : 816-23. https://doi.org/10.1016/0046-8177(95)90001-2
  39. Del Bo R, Angeretti N, Lucca E, De Simoni MG, Forloni G. Reciprocal control of inflammatory cytokines, IL-1 and IL-6, and ${\beta}$-amyloid production in cultures. Neurosci Lett. 1995 ; 188(1) : 70-4. https://doi.org/10.1016/0304-3940(95)11384-9
  40. Pan MH, Lai CS, Ho CT. Anti-inflammatory activity of natural dietary flavonoids. Food Funct. 2010 ; 1(1) : 15-31. https://doi.org/10.1039/c0fo00103a
  41. Lee P, Lee J, Kim S, Lee M-S, Yagita H, Kim SY, et al. NO as an autocrine mediator in the apoptosis of activated microglial cells: correlation between activation and apoptosis of microglial cells. Brain Res. 2001 ; 892(2) : 380-5. https://doi.org/10.1016/S0006-8993(00)03257-1
  42. Youssef S, Steinman L. At once harmful and beneficial: the dual properties of $NF-{\kappa}B$. Nat Immunol. 2006 ; 7(9) : 901-2. https://doi.org/10.1038/ni0906-901