DOI QR코드

DOI QR Code

The Stem Bark of Kalopanax pictus Exhibits Anti-inflammatory Effect through Heme Oxygenase-1 Induction and NF-${\kappa}B$ Suppression

  • Bang, Soo-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, Ga-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Park, Sun-Young (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Kim, Ji-Hee (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Lee, Yun-Kyoung (Department of Molecular Biology, College of Natural Sciences, Pusan National University) ;
  • Lee, Sang-Joon (Department of Microbiology, College of Natural Sciences, Pusan National University) ;
  • Kim, Young-Hee (Department of Molecular Biology, College of Natural Sciences, Pusan National University)
  • Received : 2010.11.02
  • Accepted : 2010.11.15
  • Published : 2010.12.31

Abstract

Backgroud: The stem bark of Kalopanax pictus (KP) has been used in traditional medicine to treat rheumatoidal arthritis, neurotic pain and diabetes mellitus in China and Korea. In this study, the mechanism responsible for anti-inflammatory effects of KP was investigated. Methods: We examined the effects of KP on NO production, nitric oxide synthase (iNOS) and HO-1 expression, NF-${\kappa}B$, Nrf2 and MAPK activation in mouse peritoneal macrophages. Results: The aqueous extract of KP inhibited LPS-induced NO secretion as well as inducible iNOS expression, without affecting cell viability. KP suppressed LPS-induced NF-${\kappa}B$ activation, phosphorylation and degradation of $I{\kappa}B-{\alpha}$, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase (JNK). Furthermore, KP induced HO-1 expression and Nrf2 nuclear translocation. Conclusion: These results suggest that KP has the inhibitory effects on LPS-induced NO production in macrophages through NF-${\kappa}B$ suppression and HO-1 induction.

Keywords

References

  1. Kim YK, Kim RG, Park SJ, Ha JH, Choi JW, Park HJ, Lee KT: In vitro antiinflammatory activity of kalopanaxsaponin A isolated from Kalopanax pictus in murine macrophage RAW 264.7 cells. Biol Pharm Bull 25;472-476, 2002 https://doi.org/10.1248/bpb.25.472
  2. Li DW, Lee EB, Kang SS, Hyun JE, Whang WK: Activityguided isolation of saponins from Kalopanax pictus with anti-inflammatory activity. Chem Pharm Bull (Tokyo) 50; 900-903, 2002 https://doi.org/10.1248/cpb.50.900
  3. Moncada S, Palmer RM, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43;109-142, 1991
  4. Southan GJ, Szabo C: Selective pharmacological inhibition of distinct nitric oxide synthase isoforms. Biochem Pharmacol 51;383-394, 1996 https://doi.org/10.1016/0006-2952(95)02099-3
  5. Pae HO, Chung HT: Heme oxygenase-1: its therapeutic roles in inflammatory diseases. Immune Netw 9;12-19, 2009 https://doi.org/10.4110/in.2009.9.1.12
  6. Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM: Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6;422-428, 2000 https://doi.org/10.1038/74680
  7. Suh GY, Jin Y, Yi AK, Wang XM, Choi AM: CCAAT/enhancer- binding protein mediates carbon monoxide-induced suppression of cyclooxygenase-2. Am J Respir Cell Mol Biol 35;220-226, 2006 https://doi.org/10.1165/rcmb.2005-0154OC
  8. Yamashita K, McDaid J, Ollinger R, Tsui TY, Berberat PO, Usheva A, Csizmadia E, Smith RN, Soares MP, Bach FH: Biliverdin, a natural product of heme catabolism, induces tolerance to cardiac allografts. FASEB J 18;765-767, 2004 https://doi.org/10.1096/fj.03-0839fje
  9. Sarady-Andrews JK, Liu F, Gallo D, Nakao A, Overhaus M, Ollinger R, Choi AM, Otterbein LE: Biliverdin administration protects against endotoxin-induced acute lung injury in rats. Am J Physiol Lung Cell Mol Physiol 289;L1131-L1137, 2005 https://doi.org/10.1152/ajplung.00458.2004
  10. Paine A, Eiz-Vesper B, Blasczyk R, Immenschuh S: Signaling to heme oxygenase-1 and its anti-inflammatory therapeutic potential. Biochem Pharmacol 80;1895-1903, 2010 https://doi.org/10.1016/j.bcp.2010.07.014
  11. Kundu JK, Surh YJ: Nrf2-Keap1 signaling as a potential target for chemoprevention of inflammation-associated carcinogenesis. Pharm Res 27;999-1013, 2010 https://doi.org/10.1007/s11095-010-0096-8
  12. Kim Y, Moon JS, Lee KS, Park SY, Cheong J, Kang HS, Lee HY, Kim HD: Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates the expression of iNOS through IKK and NF-kappaB activity in LPS-stimulated mouse peritoneal macrophages and RAW 264.7 cells. Biochem Biophys Res Commun 314;695-703, 2004 https://doi.org/10.1016/j.bbrc.2003.12.153
  13. Bubici C, Papa S, Dean K, Franzoso G: Mutual cross-talk between reactive oxygen species and nuclear factor-kappa B: molecular basis and biological significance. Oncogene 25;6731-6748, 2006 https://doi.org/10.1038/sj.onc.1209936
  14. Lee KT, Sohn IC, Park HJ, Kim DW, Jung GO, Park KY: Essential moiety for antimutagenic and cytotoxic activity of hederagenin monodesmosides and bisdesmosides isolated from the stem bark of Kalopanax pictus. Planta Med 66; 329-332, 2000 https://doi.org/10.1055/s-2000-8539
  15. Li DW, Hyun JE, Jeong CS, Kim YS, Lee EB: Antiinflammatory activity of alpha-hederin methyl ester from the alkaline hydrolysate of the butanol fraction of Kalopanax pictus bark extract. Biol Pharm Bull 26;429-433, 2003 https://doi.org/10.1248/bpb.26.429
  16. Choi J, Huh K, Kim SH, Lee KT, Kwon SH, Park HJ: Toxicology of Kalopanax pictus extract and hematological effect of the isolated anti-rheumatoidal kalopanaxsaponin A on the Freunds complete adjuvant reagent-treated rat. Arch Pharm Res 24;119-125, 2001 https://doi.org/10.1007/BF02976479
  17. Choi J, Huh K, Kim SH, Lee KT, Lee HK, Park HJ: Kalopanaxsaponin A from Kalopanax pictus, a potent antioxidant in the rheumatoidal rat treated with Freund's complete adjuvant reagent. J Ethnopharmacol 79;113-118, 2002 https://doi.org/10.1016/S0378-8741(01)00382-8
  18. Choi J, Huh K, Kim SH, Lee KT, Park HJ, Han YN: Antinociceptive and anti-rheumatoidal effects of Kalopanax pictus extract and its saponin components in experimental animals. J Ethnopharmacol 79;199-204, 2002 https://doi.org/10.1016/S0378-8741(01)00383-X
  19. Kim DH, Bae EA, Han MJ, Park HJ, Choi JW: Metabolism of kalopanaxsaponin K by human intestinal bacteria and antirheumatoid arthritis activity of their metabolites. Biol Pharm Bull 25;68-71, 2002 https://doi.org/10.1248/bpb.25.68
  20. Park HJ, Kwon SH, Lee JH, Lee KH, Miyamoto K, Lee KT: Kalopanaxsaponin A is a basic saponin structure for the anti- tumor activity of hederagenin monodesmosides. Planta Med 67;118-121, 2001 https://doi.org/10.1055/s-2001-11516
  21. Park HJ, Kim DH, Choi JW, Park JH, Han YN: A potent anti-diabetic agent from Kalopanax pictus. Arch Pharm Res 21;24-29, 1998 https://doi.org/10.1007/BF03216748
  22. Kim DW, Bang KH, Rhee YH, Lee KT, Park HJ: Growth inhibitory activities of kalopanaxsaponins A and I against human pathogenic fungi. Arch Pharm Res 21;688-691, 1998 https://doi.org/10.1007/BF02976758
  23. Kim IT, Park YM, Shin KM, Ha J, Choi J, Jung HJ, Park HJ, Lee KT: Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, Pueraria thunbergiana and Rhus verniciflua. J Ethnopharmacol 94;165-173, 2004 https://doi.org/10.1016/j.jep.2004.05.015
  24. Vareille M, Rannou F, Thelier N, Glasser AL, de Sablet T, Martin C, Gobert AP: Heme oxygenase-1 is a critical regulator of nitric oxide production in enterohemorrhagic Escherichia coli-infected human enterocytes. J Immunol 180;5720-5726, 2008 https://doi.org/10.4049/jimmunol.180.8.5720
  25. Takagi T, Naito Y, Uchiyama K, Yoshikawa T: The role of heme oxygenase and carbon monoxide in inflammatory bowel disease. Redox Rep 15;193-201, 2010 https://doi.org/10.1179/174329210X12650506623889
  26. Burgess A, Li M, Vanella L, Kim DH, Rezzani R, Rodella L, Sodhi K, Canestraro M, Martasek P, Peterson SJ, Kappas A, Abraham NG: Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice. Hypertension 56;1124-1130, 2010 https://doi.org/10.1161/HYPERTENSIONAHA.110.151423
  27. Yin H, Li X, Gong Q, Jin X, Gu H, Yuan B, Zhang B, Zheng F, Gong F, Zhu J: Heme oxygenase-1 upregulation improves lipopolysaccharide-induced acute lung injury involving suppression of macrophage migration inhibitory factor. Mol Immunol 47;2443-2449, 2010 https://doi.org/10.1016/j.molimm.2010.06.013
  28. Wu ML, Ho YC, Yet SF: A central role of heme oxygenase- 1 in cardiovascular protection. Antioxid Redox Signal 2010 [Epub ahead of print]
  29. Mandal P, Pritchard MT, Nagy LE: Anti-inflammatory pathways and alcoholic liver disease: role of an adiponectin/interleukin- 10/heme oxygenase-1 pathway. World J Gastroenterol 16;1330-1336, 2010 https://doi.org/10.3748/wjg.v16.i11.1330
  30. Wiesel P, Patel AP, DiFonzo N, Marria PB, Sim CU, Pellacani A, Maemura K, LeBlanc BW, Marino K, Doerschuk CM, Yet SF, Lee ME, Perrella MA: Endotoxin-induced mortality is related to increased oxidative stress and end-organ dysfunction, not refractory hypotension, in heme oxygenase-1-deficient mice. Circulation 102;3015-3022, 2000 https://doi.org/10.1161/01.CIR.102.24.3015
  31. Radhakrishnan N, Yadav SP, Sachdeva A, Pruthi PK, Sawhney S, Piplani T, Wada T, Yachie A: Human heme oxygenase-1 deficiency presenting with hemolysis, nephritis, and asplenia. J Pediatr Hematol Oncol 33;74-78, 2011 https://doi.org/10.1097/MPH.0b013e3181fd2aae

Cited by

  1. 해동피 및 유사생약 추출물의 위 손상에 대한 효과 vol.28, pp.4, 2010, https://doi.org/10.13103/jfhs.2013.28.4.367
  2. Enhanced biosynthesis of saponins by coronatine in cell suspension culture of Kalopanax septemlobus vol.8, pp.1, 2010, https://doi.org/10.1007/s13205-018-1090-9
  3. 생물전환을 통한 음나무발효물의 LPS에 대한 경쟁적 억제제 효과 및 내독소혈증 억제 효과 vol.32, pp.2, 2019, https://doi.org/10.9799/ksfan.2019.32.2.106