The Korean Journal of Food And Nutrition (한국식품영양학회지)

The Korean Society of Food and Nutrition (한국식품영양학회)
권호 표지
DOI QR코드

DOI QR Code

Analysis of Major Constituents of an Ethanol Extract of Platycodon Grandiflorum Leaves and Protective Effects on Inflammation in Murine Macrophage and Human Lung Carcinoma Cells

도라지 잎 에탄올 추출물의 주요 성분 분석 및 마우스 대식세포와 인체 폐암세포에서 항염효과

  • 이정민 (호서대학교 대학원 생명공학과) ;
  • 배병준 (호서대학교 대학원 생명공학과) ;
  • 최지림 ((주)황초원 ) ;
  • 정영신 (호서대학교 생명공학과 )
  • Received : 2024.02.14
  • Accepted : 2024.04.17
  • Published : 2024.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study investigated major constituents and anti-inflammatory effects of an ethanol extract of Platycodon grandiflorum leaves. Through HPLC analysis, chlorogenic acid and luteolin-7-O-glucoside were identified as predominant constituents in the ethanol extract. Their anti-inflammatory effects were evaluated using murine macrophage (RAW 264.7 cells) and human lung carcinoma cells (NCI-H292 & A549). The ethanol extract significantly (p<0.01) inhibited the production of nitrite, interleukin-6 (IL-6), and prostaglandin E2 (PGE2) induced by lipopolysaccharide (LPS) in RAW 264.7 cells. Furthermore, the ethanol extract suppressed the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) proteins in RAW 264.7 cells stimulated with LPS. In NCI-H292 and A549 cells, treatment with the ethanol extract significantly (p<0.05) decreased levels of pro-inflammatory cytokines IL-6 and IL-8 induced by IL-1β. The phosphorylation of ERK rather than JNK in the mitogen-activated protein kinase signaling pathway was observed to be a more important mediator in the down-regulation of pro-inflammatory cytokines in NCI-H292 cells. These findings suggest that the ethanol extract of Platycodon grandiflorum leaves containing luteolin-7-O-glucoside exhibits promising anti-inflammatory properties.

Keywords

Acknowledgement

본 연구는 2020년도 중소벤처기업부 창업성장기술개발사업 전략형 창업과제(Big3, S287589) 연구비 지원으로 수행되었으며 이에 감사드립니다. 2022년도 호서대학교 연구년 결과물로 제출됩니다.

References

  1. Ahn KS, Noh EJ, Zhao HL, Jung SH, Kang SS, Kim YS. 2005. Inhibition of inducible nitric oxide synthase and cyclooxygenase II by Platycodon grandiflorum saponins via suppression of nuclear factor-κB activation in RAW 264.7 cells. Life Sci 76:2315-2328 https://doi.org/10.1016/j.lfs.2004.10.042
  2. Andlauer W, Kolb J, Fürst P. 2000. Isoflavones from tofu are absorbed and metabolized in the isolated rat small intestine. J Nutr 130:3021-3027 https://doi.org/10.1093/jn/130.12.3021
  3. Aziz N, Kim MY, Cho JY. 2018. Anti-inflammatory effects of luteolin: A review of in vitro, in vivo, and in silico studies. J Ethnopharmacol 225:342-358 https://doi.org/10.1016/j.jep.2018.05.019
  4. Bailly C, Vergoten G. 2020. Proposed mechanisms for the extracellular release of PD-L1 by the anticancer saponin platycodin D. Int Immunopharmacol 85:106675
  5. Behl T, Upadhyay T, Singh S, Chigurupati S, Alsubayiel AM, Mani V, Vargas-De-La-Cruz C, Uivarosan D, Bustea C, Sava C, Stoicescu M, Radu AF, Bungau SG. 2021. Polyphenols targeting MAPK mediated oxidative stress and inflammation in rheumatoid arthritis. Molecules 26:6570
  6. Biesalski HK. 2007. Polyphenols and inflammation: Basic interactions. Curr Opin Clin Nutr Metab Care 10:724-728 https://doi.org/10.1097/MCO.0b013e3282f0cef2
  7. Boost KA, Sadik CD, Bachmann M, Zwissler B, Pfeilschifter J, Muhl H. 2008. IFN-gamma impairs release of IL-8 by IL-1beta-stimulated A549 lung carcinoma cells. BMC Cancer 8:2656
  8. Caporali S, De Stefano A, Calabrese C, Giovannelli A, Pieri M, Savini I, Tesauro M, Bernardini S, Minieri M, Terrinoni A. 2022. Anti-inflammatory and active biological properties of the plant-derived bioactive compounds luteolin and luteolin 7-glucoside. Nutrients 14:1155
  9. Chahar MK, Sharma N, Dobhal MP, Joshi YC. 2011. Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev 5:1-12 https://doi.org/10.4103/0973-7847.79093
  10. Czeczot H, Tudek B, Kusztelak J, Szymczyk T, Dobrowolska B, Glinkowska G, Malinowski J, Strzelecka H. 1990. Isolation and studies of the mutagenic activity in the Ames test of flavonoids naturally occurring in medical herbs. Mutat Res 240:209-216 https://doi.org/10.1016/0165-1218(90)90060-F
  11. De Stefano A, Caporali S, Di Daniele N, Rovella V, Cardillo C, Schinzari F, Minieri M, Pieri M, Candi E, Bernardini S, Tesauro M, Terrinoni A. 2021. Anti-inflammatory and proliferative properties of luteolin-7-O-glucoside. Int J Mol Sci 22:1321
  12. Domitrovic R, Cvijanovic O, Pugel EP, Zagorac GB, Mahmutefendic H, Skoda M. 2013. Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney. Toxicology 310:115-123 https://doi.org/10.1016/j.tox.2013.05.015
  13. Douglas CC, Johnson SA, Arjmandi BH. 2013. Soy and its isoflavones: The truth behind the science in breast cancer. Anticancer Agents Med Chem 13:1178-1187 https://doi.org/10.2174/18715206113139990320
  14. Gao W, Wang C, Yu L, Sheng T, Wu Z, Wang X, Zhang D, Lin Y, Gong Y. 2019. Chlorogenic acid attenuates dextran sodium sulfate-induced ulcerative colitis in mice through MAPK/ERK/JNK pathway. BioMed Res Int 2019:6769789
  15. Ha YW, Kim YS. 2009. Preparative isolation of six major saponins from Platycodi Radix by high-speed countercurrent chromatography. Phytochem Anal 20:207-213 https://doi.org/10.1002/pca.1116
  16. Horvathova K, Chalupa I, Sebova L, Tothova D, Vachalkova, A. 2005. Protective effect of quercetin and luteolin in human melanoma HMB-2 cells. Mutat Res 565:105-112 https://doi.org/10.1016/j.mrgentox.2004.08.013
  17. Hu C, Kitts DD. 2004. Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW264.7 cells. Mol Cell Biochem 265:107-113 https://doi.org/10.1023/B:MCBI.0000044364.73144.fe
  18. Huang J, Xie M, He L, Song X, Cao T. 2023. Chlorogenic acid: A review on its mechanisms of anti-inflammation, disease treatment, and related delivery systems. Front Pharmacol 14:1218015
  19. Hulina-Tomaskovic A, Grdic Rajkovic M, Jelic D, Bosnar M, Sladoljev L, Zanic Grubisic T, Rumora L. 2019. Proinflammatory effects of extracellular Hsp70 on NCI-H292 human bronchial epithelial cell line. Int J Exp Pathol 100:320-329 https://doi.org/10.1111/iep.12335
  20. Inada A, Murata H, Somekawa M, Nakanishi T. 1992. Phytochemical studies of seeds of medicinal plants II. A new dihydroflavonol glycoside and a new 3-methyl-l-butanol glycoside from seeds of Platycodon grandiflorum A. DE CANDOLLE. Chem Pharm Bull 40:3081-3083 https://doi.org/10.1248/cpb.40.3081
  21. Jeon YS, Kim MW. 2011. The antioxidative effects and isolation and characterization of the extracts from Morus alba L. Korean J Food Nutr 24:94-100 https://doi.org/10.9799/ksfan.2011.24.1.094
  22. Jeong CH, Choi GN, Kim JH, Kwak JH, Kim DO, Kim YJ, Heo HJ. 2010. Antioxidant activities from the aerial parts of Platycodon grandiflorum. Food Chem 118:278-282 https://doi.org/10.1016/j.foodchem.2009.04.134
  23. Ji JD, Lee YH, Song GG. 2004. Prostaglandin E2 (PGE2): Roles in immune responses and inflammation. J Rheum Dis 11:307-316
  24. Ji MY, Bo A, Yang M, Xu JF, Jiang LL, Zhou BC, Li MH. 2020. The pharmacological effects and health benefits of Platycodon grandiflorus: A medicine food homology species. Foods 9:142
  25. Jin M, Son KH, Chang HW. 2011. Luteolin-7-O-glucoside suppresses leukotriene C4 production and degranulation by inhibiting the phosphorylation of mitogen activated protein kinases and phospholipase Cγ1 in activated mouse bone marrow-derived mast cells. Biol Pharm Bull 34:1032-1036 https://doi.org/10.1248/bpb.34.1032
  26. Jung JI, Lee HS, Kim SM, Kim S, Lim J, Woo M, Kim EJ. 2022. Immunostimulatory activity of hydrolyzed and fermented Platycodon grandiflorum extract occurs via the MAPK and NF-κB signaling pathway in RAW 264.7 cells. Nutr Res Pract 16:685-699 https://doi.org/10.4162/nrp.2022.16.6.685
  27. Kang JM, Yeo SW, Lee HY, Chang KH, Suh BD. 2000. Effect of antioxidants and dexamethasone on inducible nitric oxide synthase expression and nitric oxide production in murine macrophage cells. Korean J Otorhinolaryngol-Head Neck Surg 43:136-142
  28. Kang KJ, Kim BH, Kim DH, Yun HJ, Cho YS, Han NE, Choi JC, Lee SN, Choi OK. 2021. Determination of the contents of apigenin and luteolin in vegetables. Korean J Food Nutr 34:233-241
  29. Kim M, Hwang IG, Kim SB, Choi AJ. 2020. Chemical characterization of balloon flower (Platycodon grandiflorum) sprout extracts and their regulation of inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 murine macrophage cells. Food Sci Nutr 8:246-256 https://doi.org/10.1002/fsn3.1297
  30. Kim SH, Park SY, Park YL, Myung DS, Rew JS, Joo YE. 2017. Chlorogenic acid suppresses lipopolysaccharide-induced nitric oxide and interleukin-1β expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells. Mol Med Rep 16:9224-9232 https://doi.org/10.3892/mmr.2017.7686
  31. Kou JJ, Shi JZ, He YY, Hao JJ, Zhang HY, Luo DM, Song JK, Yan Y, Xie XM, Du GH, Pang XB. 2022. Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation. Acta Pharmacol Sin 43:840-849 https://doi.org/10.1038/s41401-021-00702-8
  32. Kozlowska A, Szostak-Wegierek D. 2014. Flavonoids-food sources and health benefits. Rocz Panstw Zakl Hig 65:79-85
  33. Lee JW, Ji SH, Kim GS, Song KS, Um Y, Kim OT, Lee Y, Hong CP, Shin DH, Kim CK, Lee SE, Ahn YS, Lee DY. 2015. Global profiling of various metabolites in Platycodon grandiflorum by UPLC-QTOF/MS. Int J Mol Sci 16:26786-26796 https://doi.org/10.3390/ijms161125993
  34. Lee JY. 2019. Antioxidant and anti-inflammatory effects of ethanol extracts from Platycodon grandiflorum leaves. Master's Thesis, Hoseo Univ. Asan. Korea
  35. Leo CH, Woodman OL. 2015. Flavonols in the prevention of diabetes-induced vascular dysfunction. J Cardiovasc Pharmacol 65:532-544 https://doi.org/10.1097/FJC.0000000000000180
  36. Leyva-Lopez N, Gutierrez-Grijalva EP, Ambriz-Perez, DL, Heredia JB. 2016. Flavonoids as cytokine modulators: A possible therapy for inflammation-related diseases. Int J Mol Sci 17:17060921
  37. Li M, Wang H, Lu Y, Cai J. 2023. Luteolin suppresses inflammation and oxidative stress in chronic obstructive pulmonary disease through inhibition of the NOX4-mediated NF-κB signaling pathway. Immun Inflamm Dis 11:e820
  38. Li T, Xu WS, Wu GS, Chen XP, Wang YT, Lu JJ. 2014. Platycodin D induces apoptosis, and inhibits adhesion, migration and invasion in HepG2 hepatocellular carcinoma cells. Asian Pac J Cancer Prev 15:1745-1749 https://doi.org/10.7314/APJCP.2014.15.4.1745
  39. Li W, Liu Y, Wang Z, Han Y, Tian YH, Zhang GS, Sun YS, Wang YP. 2015. Platycodin D isolated from the aerial parts of Platycodon grandiflorum protects alcohol-induced liver injury in mice. Food Funct 6:1418-1427 https://doi.org/10.1039/C5FO00094G
  40. Li YC, Yeh CH, Yang ML, Kuan YH. 2012. Luteolin suppresses inflammatory mediator expression by blocking the Akt/NFκB pathway in acute lung injury induced by lipopolysaccharide in mice. Evid Based Complement Alternat Med 2012:383608
  41. Mazol I, Glensk M, Cisowski W. 2004. Polyphenolic compounds from Platycodon grandiflorum A. DC. Acta Pol Pharm 61:203-208
  42. Mortele O, Jorissen J, Spacova I, Lebeer S, van Nuijs ALN, Hermans N. 2021. Demonstrating the involvement of an active efflux mechanism in the intestinal absorption of chlorogenic acid and quinic acid using a Caco-2 bidirectional permeability assay. Food Funct 12:417-425 https://doi.org/10.1039/D0FO02629H
  43. Mueller M, Hobiger S, Jungbauer A. 2010. Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem 122:987-996 https://doi.org/10.1016/j.foodchem.2010.03.041
  44. Nabavi SF, Braidy N, Gortzi O, Sobarzo-Sanchez E, Daglia M, Skalicka-Wozniak K, Nabavi SM. 2015. Luteolin as an anti-inflammatory and neuroprotective agent: A brief review. Brain Res Bull 119:1-11 https://doi.org/10.1016/j.brainresbull.2015.09.002
  45. Palombo R, Caporali S, Falconi M, Iacovelli F, Morozzo Della Rocca B, Lo Surdo A, Campione E, Candi E, Melino G, Bernardini S, Terrinoni A. 2019. Luteolin-7-O-β-D-glucoside inhibits cellular energy production interacting with HEK2 in keratinocytes. Int J Mol Sci 20:2689
  46. Palombo R, Savini I, Avigliano L, Madonna S, Cavani A, Albanesi C, Mauriello A, Melino G, Terrinoni A. 2016. Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model. Cell Death Dis 7:e2344
  47. Panche AN, Diwan AD, Chandra SR. 2016. Flavonoids: An overview. J Nutr Sci 5:e47
  48. Park CM, Song YS. 2013. Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-κB/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells. Nutr Res Pract 7:423-429 https://doi.org/10.4162/nrp.2013.7.6.423
  49. Park CM, Song YS. 2019. Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice. Nutr Res Pract 13: 473-479 https://doi.org/10.4162/nrp.2019.13.6.473
  50. Rafacho BPM, Stice CP, Liu C, Greenberg AS, Ausman LM, Wang XD. 2015. Inhibition of diethylnitrosamine-initiated alcohol-promoted hepatic inflammation and precancerous lesions by flavonoid luteolin is associated with increased sirtuin 1 activity in mice. Hepatobiliary Surg Nutr 4:124-134 https://doi.org/10.1096/fasebj.28.1_supplement.829.7
  51. Santana-Galvez J, Cisneros-Zevallos L, Jacobo-Velazquez DA. 2017. Chlorogenic acid: Recent advances on its dual role as a food additive and a nutraceutical against metabolic syndrome. Molecules 22:358
  52. Seelinger G, Merfort I, Schempp CM. 2008. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta Med 74:1667-1677 https://doi.org/10.1055/s-0028-1088314
  53. Shan J, Fu J, Zhao Z, Kong X, Huang H, Luo L, Yin Z. 2009. Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW264. 7 cells through suppressing NF-κB and JNK/AP-1 activation. Int Immunopharmacol 9:1042-1048 https://doi.org/10.1016/j.intimp.2009.04.011
  54. Shen Q, Zhong YT, Liu XX, Hu JN, Qi SM. Li K, Wang Z, Zhu HY, Li XD, Wang YP, Li W. 2023. Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD/STZ-induced type 2 diabetic mice. Food Funct 14:74-86 https://doi.org/10.1039/D2FO03308A
  55. Shimoi K, Okada H, Furugori M, Goda T, Takase S, Suzuki, M, Hara Y, Yamamoto H, Kinae N. 1998. Intestinal absorption of luteolin and luteolin 7-O-β-glucoside in rats and humans. FEBS lett 438:220-224 https://doi.org/10.1016/S0014-5793(98)01304-0
  56. Shin CY, Lee WJ, Lee EB, Choi EY, Ko KH. 2002. Platycodin D and D3 increase airway mucin release in vivo and in vitro in rats and hamsters. Planta Med 68:221-225 https://doi.org/10.1055/s-2002-23130
  57. Song YS, Park CM. 2014. Luteolin and luteolin-7-O-glucoside strengthen antioxidative potential through the modulation of Nrf2/MAPK mediated HO-1 signaling cascade in RAW 264.7 cells. Food Chem Toxicol 65:70-75 https://doi.org/10.1016/j.fct.2013.12.017
  58. Tanaka T, Narazaki M, Kishimoto T. 2014. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 6:a016295
  59. Trivedi HR, Puranik PK. 2023. Chlorogenic acid-optimized nanophytovesicles: A novel approach for enhanced permeability and oral bioavailability. Future J Pharm Sci 9:116
  60. Wang C, Zhang N, Wang Z, Qi Z, Zhu H, Zheng B, Li P, Liu J. 2017. Nontargeted metabolomic analysis of four different parts of Platycodon grandiflorum grown in northeast China. Molecules 22:1280
  61. Wang J, Mazza G. 2002. Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-γ-activated RAW 264.7 macrophages. J Agric Food Chem 50:850-857 https://doi.org/10.1021/jf010976a
  62. Wittemer SM, Ploch M, Windeck T, Muller SC, Drewelow B, Derendorf H, Veit M. 2005. Bioavailability and pharmacokinetics of caffeoylquinic acids and flavonoids after oral administration of artichoke leaf extracts in humans. Phytomedicine 12:28-38 https://doi.org/10.1016/j.phymed.2003.11.002
  63. Wu J, Yang G, Zhu W, Wen W, Zhang F, Yuan J, An L. 2012. Anti-atherosclerotic activity of platycodin D derived from roots of Platycodon grandiflorum in human endothelial cells. Biol Pharm Bull 35:1216-1221 https://doi.org/10.1248/bpb.b-y110129
  64. Xiong J, Wang K, Yuan C, Xing R, Ni J, Hu G, Chen F, Wang X. 2017. Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects. Int J Mol Med 39:113-125 https://doi.org/10.3892/ijmm.2016.2809
  65. Zhang L, Wang Y, Yang D, Zhang C, Zhang N, Li M, Liu Y. 2015. Platycodon grandiflorus: An ethnopharmacological, phytochemical and pharmacological review. J Ethnopharmacol 164:147-161 https://doi.org/10.1016/j.jep.2015.01.052
  66. Zubik L, Meydani M. 2003. Bioavailability of soybean isoflavones from aglycone and glucoside forms in American women. Am J Clin Nutr 77:1459-1465 https://doi.org/10.1093/ajcn/77.6.1459