The Journal of Korean Obstetrics and Gynecology (대한한방부인과학회지)

The Society of Korean Medicine Obstetrics and Gynecology (대한한방부인과학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Gamijipaesan Extracts against Mastitis Induced by Staphylococcus aureus Infection in a Rat Model through Anti-inflammatory and Antibacterial Effects

가미지패산(加味芷貝散)의 포도상구균 감염 유방염에 대한 항균활성 및 항염 효과

  • Kwon, Ji-Myung (Dept. of Oriental Obstetric & Gynecology, College of Oriental Medicine, Daegu Haany University) ;
  • Kim, Dong-Chul (Dept. of Oriental Obstetric & Gynecology, College of Oriental Medicine, Daegu Haany University)
  • 권지명 (대구한의대학교 한의과대학 부인과 교실) ;
  • 김동철 (대구한의대학교 한의과대학 부인과 교실)
  • Received : 2013.01.23
  • Accepted : 2013.02.08
  • Published : 2013.02.22
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: The object of this study was to observe the protective effect of Gamijipaesan aqueous extracts(GJS), which has been traditionally used in Korean medicine in obstetrics & gynecological fields as anti-infectious and anti-inflammatory agents, against mastitis induced by Staphylococcus aureus infection in a rat model through antibacterial, antiinflammatory, immunomodulatory, and anti-oxidant effects. Methods: Antibacterial activities of GJS against S. aureus were detected using standard agar microdilution methods, with the effects on the bacterial invasion and intracellular killing of individual test materials in human mammary gland carcinoma cell(MCF-7) and murine macrophages(Raw 264.7) at MIC1/2, MIC and MIC2 concentration levels. In addition, the effects on the cell viability, nitric oxide(NO), tumor necrosis factor(TNF)-${\alpha}$ and interleukin (IL)-6 productions of LPS activated Raw 264.7 cells. The changes on the mammary tissue viable bacterial numbers, myeloperoxidae(MPO), inducible nitric oxide synthetase(iNOS), TNF-${\alpha}$ and IL-6 contents were observed in the S. aureus in vivo intramammary infectious rat model. The anti-bacterial and anti-inflammatory effects were compared with ciprofloxacin and piroxicam, respectively in the present study. Results: MIC of GJS and ciprofloxacin against S. aureus were detected as $0.860{\pm}0.428$ (0.391-1.563) mg/ml and $0.371{\pm}0.262$(0.098-0.782) ${\mu}g/ml$, respectively. In addition, GJS and ciprofloxacin were also showed marked dosage-dependent inhibition of the both bacterial invasion and intracellular killing assays using MCF-7 and Raw 264.7 cells at MIC1/2, MIC and $MIC{\times}2$ concentrations, respectively. $ED_{50}$ against LPS-induced cell viabilities and NO, TNF-${\alpha}$ and IL-6 releases of GJS were detected as 0.72, 0.04, 0.08 and 0.11 mg/ml, and as 19.04, 4.18, 5.37 and 4.27 ${\mu}g/ml$ in piroxicam, respectively. 250 and 500 mg/kg of GJS also inhibit the intramammary bacterial growth, MPO, iNOS, TNF-${\alpha}$ and IL-6 contents in S. aureus in vivo intramammary infected rats, respectively. GJS 500 mg/kg showed quite similar antibacterial and anti-infectious effects as compared with ciprofloxacin 40 mg/kg and also showed similar anti-inflammatory effects as piroxicam 10 mg/kg, in S. aureus in vivo intramammary infectious models. Conclusions: The results obtained in this study suggest that over 250 mg/kg of GJS showed favorable anti-infectious effects against S. aureus infection in a rat model through their antibacterial, anti-inflammatory, immunomodulatory and anti-oxidant effects and therefore expected that GJS can be used as alternative therapies, having both anti-inflammatory and anti-infectious activities. However, more detail mechanism studies should be conducted in future with the efficacy tests of individual herbal composition of GJS and the screening of the biological active compounds in individual herbs. In the present study, GJS 500 mg/kg showed quite similar anti-infectious effects were detected as compared with ciprofloxacin 40 mg/kg treated rats, and also GJS shows quite similar anti-inflammatory effects as compared with piroxicam 10 mg/kg in S. aureus in vivo intramammary infectious rats, but ciprofloxacin did not showed any anti-inflammatory effects, and piroxicam did not showed anti-infectious effects in this study.

Keywords

References

  1. Foxman B et al. Lactation mastitis: occurrence and medical management among 946 breastfeeding women in the United States. Am J Epidemiol. 2002;155(2):103-14. https://doi.org/10.1093/aje/155.2.103
  2. 노동영 등. 양성유방질환의 임상적 역학적 연구. 대한외과학회지. 1993;44(6) :797-808.
  3. Spencer JP. Management of mastitis in breastfeeding women. Am Fam Physician. 2008;78(6):727-31.
  4. Franklin D. Lowy, M.D. Staphylococcus aureus infections. N Engl J Med. 1998; 339(8):520-32. https://doi.org/10.1056/NEJM199808203390806
  5. Grundmann H et al. Emergence and resurgence of methicillin-resistant Staphylococcus aureus as public-health threat. Lancet. 2006;368(9538):874-5. https://doi.org/10.1016/S0140-6736(06)68853-3
  6. Kapil A. The challenge of antibiotic resistance: need to contemplate. Indian Journal of Medical Research. 2005; 121(2):83-91.
  7. Okamoto R, Okubo T, Inoue M. Detection of genes regulating betalactamase production in Enterococcus faecalis and Staphylococcus aureus. Antimicrob Agents Chemother. 1996; 40(11):2550-4.
  8. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999;340(24):1888-99. https://doi.org/10.1056/NEJM199906173402407
  9. McDaniel ML et al. Cytokines and nitric oxide in islet inflammation and diabetes. Proc Soc Exp Biol Med. 1996;211(1):24-32. https://doi.org/10.3181/00379727-211-43950D
  10. 김대희 등. LPS로 활성화된 대식세포 에서 黃連解毒湯 물추출물의 염증매개물질 억제효과. 大韓本草學會誌. 2009; 24:39-47.
  11. 대한한방부인과학회. 한방여성의학. 서울:의성당. 2013:818.
  12. 李梴. 醫學入門. 서울:輸成社. 1984:464.
  13. 陳實功. 外科正宗. 北京:인민위생출판사. 1983:30, 144-50.
  14. 李定濟. 醫療要覽(上). 서울:동양의약 연구원. 1974:383.
  15. 陳自明. 校註婦人良方大全. 臺北:文光 圖書. 1989:71-5.
  16. 張介賓. 景岳全書. 서울:輸成社. 1983 :725.
  17. 武之望. 濟陰綱目. 臺北:旋風出版社. 1977:557.
  18. 葉桂. 葉天士女科全書. 臺北:力行書局. 1975:118.
  19. 吳謙 外. 醫宗金鑑. 서울:대성문화사. 1983:236-7.
  20. 許浚. 東醫寶鑑. 서울:法仁文化社. 2005 :1260.
  21. 蕭損. 女科經綸. 江蘇:江蘇科學技術出版社. 1986:332-8.
  22. 萬病回春. 龔廷賢. 서울:일중사. 1991 :120.
  23. 장성환, 김윤상, 임은미. 유선염의 한방외치법에 대한 문헌 고찰. 대한한방부인과학회지. 2002;15(3):177-22.
  24. 이상현, 박찬기. 지패산의 항염증 효능에 대한 연구. 대한한의학방제학회지. 2008;16(1):79-94.
  25. 김정숙 등. 유옹에 활용되는 가감유 기음에 대한 실험적 연구. 대한한방부인과학회지. 1995;8(1):115-30.
  26. 백성준, 정진홍, 유동열. 유옹(乳癰)에 활용되는 가미소독음(加味消毒飮)의 진통(鎭痛), 소염(消炎)작용에 대한 연구. 대한한방부인과학회지. 1997;10(1) :51-61.
  27. 이한철. 加味芷貝散이 實驗動物의 鎭痛, 消炎, 解熱 및 抗菌에 미치는 影響. 원광대학교석사학위논문. 1998.
  28. 최창민, 이종덕, 유성원. 비수유기 유선염 및 유방농양 환자 증례보고. 대한한방부인과학회지. 2006;19(2):295-304.
  29. 이자영 등. 탁리소독음으로 치료한 유옹 환자 2례. 대한한방부인과학회지. 2007;20(4):191-201.
  30. 서부일, 김민정. 산후우울증과 급성 울체성유선염 합병증 환자의 임상치료 1례. 대한본초학회지. 2003;18(1):145-8.
  31. 황도연. 方藥合編. 서울:남산당. 1978 :248-9.
  32. Institute for Laboratory Animal Research. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington, D.C. :The national academic spress. 1985 :162-6.
  33. Pfaller MA et al. Collaborative investigation of variables in susceptibility testing of yeasts. Antimicrob Agents Chemother. 1990;34(9):1648-54. https://doi.org/10.1128/AAC.34.9.1648
  34. Tenover FC et al. Characterization of staphylococci with reduced susceptibilities to vancomycin and other glycopeptides. J Clin Microbiol. 1998;36(4):1020-7.
  35. Pfaller MA, Burmeister L, Bartlett MS, Rinaldi MG. Multicenter evaluation of four methods of yeast inoculum preparation. J Clin Microbiol. 1988; 26(8):1437-41.
  36. Cuffini AM et al. Enhanced Staphylococcus aureus susceptibility to immuno-defense induced by sub-inhibitory and bactericidal concentration of imipenem. J Antimicrob Chemotherp. 1993;31(4):559-68. https://doi.org/10.1093/jac/31.4.559
  37. Almeida RA et al. Staphylococcus aureus invasion of bovine mammary epithelial cells. J Dairy Sci. 1996;79(6):1021-6. https://doi.org/10.3168/jds.S0022-0302(96)76454-8
  38. Menzies BE, Kourteva I. Internalisation of Staphylococcus aureus by endothelial cells induces apoptosis. Infect Immunol. 1998;66(12):5994-8.
  39. Guinea J et al. In vitro and in vivo antibacterial activities of E-4868, a new fluoroquinolone with a 7-azetidin ring substituent. Antimicrob Agents Chemother. 1993;37(4):868-74. https://doi.org/10.1128/AAC.37.4.868
  40. Murase A et al. Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation. Eur J Pharmacol. 2008;580(1-2):116-21. https://doi.org/10.1016/j.ejphar.2007.10.054
  41. Zhong K et al. Establishment of experimental mastitis model by endotoxin via teat duct in rat. J Agric Biotechnol. 2005;13:654-8.
  42. Kavutcu M et al. Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. Nephron. 1996;72(2):269-74. https://doi.org/10.1159/000188853
  43. Lowry OH et al. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75.
  44. Gonen E et al. Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis. Cell Microbiol. 2007;9(12):2826-38. https://doi.org/10.1111/j.1462-5822.2007.00999.x
  45. Miao J et al. The effect of taurine on the toll-like receptors/nuclear factor kappa B (TLRs/NF-${\kappa}B$) signaling pathway in Streptococcus uberis-induced mastitis in rats. Int Immunopharmacol. 2011;11(11):1740-6. https://doi.org/10.1016/j.intimp.2011.06.008
  46. Zhu YM, Miao JF, Fan HJ, Zou SX, Chen WH. Protective effect of CpG-DNA against mastitis induced by Staphylococcus aureus infection in a rat model. Int Immunopharmacol. 2007;7(4):435-43. https://doi.org/10.1016/j.intimp.2006.10.008
  47. 朱震亨. 丹溪心法附餘. 태북:오주출판사. 1981:552.
  48. 顧伯康. 中醫外科學. 북경:인민위생출판사. 1987:153-61.
  49. 김동현 등. 한방약리학. 서울:신일상사. 2010:116-23, 134, 135, 167-72, 262-5, 325-8, 345-52, 689-92, 786, 787.
  50. 김인락 등. 本草學. 서울:圖書出版永林社. 2007:467-9.
  51. Lechner D et al. The anti-staphylococcal activity of Angelica dahurica(Bai Zhi). Phytochemistry. 2004;65(3):331-5. https://doi.org/10.1016/j.phytochem.2003.11.010
  52. Lee MY et al. Anti-inflammatory activity of Angelica dahurica ethanolic extract on RAW264.7 cells via upregulation of heme oxygenase-1. Food Chem Toxicol. 2011;49(5):1047-55. https://doi.org/10.1016/j.fct.2011.01.010
  53. Lee MY et al. Anti-asthmatic effects of Angelica dahurica against ovalbumin -induced airway inflammation via upregulation of heme oxygenase-1. Food Chem Toxicol. 2011;49(4):829-37. https://doi.org/10.1016/j.fct.2010.12.004
  54. Kang SW et al. Rapid identification of furanocoumarins in Angelica dahurica using the online LC-MMR-MS and their nitric oxide inhibitory activity in RAW 264.7 cells. Phytochem Anal. 2010;21(4):322-7. https://doi.org/10.1002/pca.1202
  55. 신용규 등. 패모(Fritillaria thunbergii Miquel)의 항균, 항혈전 및 항산화 활성 평가. 생명과학회지. 2009;19(9) :1245-50.
  56. Cho IH et al. Fritillaria ussuriensis extract inhibits the production of inflammatory cytokine and MAPKs in mast cells. Biosci Biotechnol Biochem. 2011;75(8):1440-5. https://doi.org/10.1271/bbb.110076
  57. Ozaki Y, Xing L, Satake M. Antiinflammatory effect of Trichosanthes kirilowii Maxim, and its effective parts. Biol Pharm Bull. 1996;19(8):1046-8. https://doi.org/10.1248/bpb.19.1046
  58. Cai Y et al. Trichosanthin enhances anti-tumor immune response in a murine Lewis lung cancer model by boosting the interaction between TSLC1 and CRTAM. Cell Mol Immunol. 2011;8(4):359-67. https://doi.org/10.1038/cmi.2011.12
  59. Bhattacharya S et al. Antitumor efficacy and amelioration of oxidative stress by Trichosanthes dioica root against Ehrlich ascites carcinoma in mice. Pharm Biol. 2011;49(9):927-35. https://doi.org/10.3109/13880209.2011.557080
  60. 배지현, 김미순, 강은혜. 식중독 유발 세균의 증식에 미치는 금은화 추출물의 항균효과. 한국식품과학회지. 2005; 37(4):642-7.
  61. Ryu KH et al. Anti-inflammatory and analgesic activities of SKLJI, a highly purified and injectable herbal extract of Lonicerajaponica. Biosci Biotechnol Biochem. 2010;74(10):2022-8. https://doi.org/10.1271/bbb.100279
  62. 한재섭, 박희수. 금은화약침(金銀花 藥鍼)의 항암 및 면역반응에 관한 실험적 연구. 대한침구학회지. 2006; 23(4):205-18.
  63. Choi CW et al. Antioxidant constituents and a new triterpenoid glycoside from Flos Lonicerae. Arch Pharm Res. 2007; 30(1):1-7. https://doi.org/10.1007/BF02977770
  64. Zhou L et al. Antibacterial phenolic compounds from the spines of Gleditsia sinensis Lam. Nat Prod Res. 2007; 21(4):283-91. https://doi.org/10.1080/14786410701192637
  65. Dai Y et al. Antiallergic and antiinflammatory properties of the ethanolic extract from Gleditsia sinensis. Biol Pharm Bull. 2002;25(9):1179-82. https://doi.org/10.1248/bpb.25.1179
  66. Chui CH et al. Gleditsia sinensis fruit extract induced growth inhibition involves basic fibroblast growth factor and nitric oxide. Int J Mol Med. 2004;13(1):169-73.
  67. 정현우, 전병훈. 백선피와 천산갑이 인체 암세포주에 미치는 세포독성의 효과. 동의병리학회지. 1997;11(1):58-64.
  68. Lee S et al. Antibacterial coumarins from Angelica gigas roots. Arch Pharm Res. 2003;26(6):449-52. https://doi.org/10.1007/BF02976860
  69. Kim WJ et al. Decursinol angelate blocks transmigration and inflammatory activation of cancer cells through inhibition of PI3K, ERK and NF-kappaB activation. Cancer Lett. 2010;296(1) :35-42. https://doi.org/10.1016/j.canlet.2010.03.012
  70. Kim HM et al. Antidiabetic activity of angelan isolated from Angelica gigas Nakai. Arch Pharm Res. 2008; 31(11):1489-96. https://doi.org/10.1007/s12272-001-2135-9
  71. Kim JH et al. Decursin prevents cisplatin-induced apoptosis via the enhancement of antioxidant enzymes in human renal epithelial cells. Biol Pharm Bull. 2010;33(8):1279-84. https://doi.org/10.1248/bpb.33.1279
  72. Fukai T et al. Antimicrobial activity of licorice flavonoids against methicillin -resistant Staphylococcus aureus. Fitoterapia. 2002;73(6):536-9. https://doi.org/10.1016/S0367-326X(02)00168-5
  73. Xie YC et al. Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice. Int Immunopharmacol. 2009;9(2):194-200. https://doi.org/10.1016/j.intimp.2008.11.004
  74. Zhang L et al. Cardioprotective effects of Glycyrrhiza uralensis extract against doxorubicin-induced toxicity. Int J Toxicol. 2011;30(2):181-9. https://doi.org/10.1177/1091581810393033
  75. Li J et al. Immunosuppressive activity on the murine immune responses of glycyrol from Glycyrrhiza uralensis via inhibition of calcineurin activity. Pharm Biol. 2010;48(10):1177-84. https://doi.org/10.3109/13880200903573169
  76. Seral C, Van Bambeke F, Tulkens PM. Quantitative analysis of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin(LY333328) activities against intracellular Staphylococcus aureus in mouse J774 macrophages. Antimicrob Agents Chemother. 2003; 47(7):2283-92. https://doi.org/10.1128/AAC.47.7.2283-2292.2003
  77. Yancey RJ, Sanchez MS, Ford CW. Activity of antibiotics against Staphylococcus aureus within polymorphonuclear neutrophils. Eur J Clin Microbiol Infect Dis. 1991;10(2):107-13. https://doi.org/10.1007/BF01964421
  78. Hebert A et al. Demonstration of intracellular Staphylococcus aureus in bovine mastitis alveolar cells and macrophages isolated from naturally infected cow milk. FEMS Microbiol Lett. 2000;193(1):57-62. https://doi.org/10.1111/j.1574-6968.2000.tb09402.x
  79. Gruet P et al. Bovine mastitis and intramammary drug delivery: review and perspectives. Adv Drug Deliv Rev. 2001;50(3):245-59. https://doi.org/10.1016/S0169-409X(01)00160-0
  80. Diarra MS et al. Lactoferrin against Staphylococcus aureus Mastitis. Lactoferrin alone or in combination with penicillin G on bovine polymorphonuclear function and mammary epithelial cells colonisation by Staphylococcus aureus. Vet Immunol Immunopathol. 2003;95(1-2):33-42. https://doi.org/10.1016/S0165-2427(03)00098-9
  81. Lee YS et al. IL-6 mRNA expression in mouse peritoneal macrophages and NIH3T3 fibroblasts in response to Candida albicans. J Microbiol Biotechnol. 2000;10(1):8-15.
  82. Chun SC et al. Anti-Inflammatory activity of the methanol extract of Moutan Cortex in LPS-activated Raw264.7 Cells. Evid Based Complement Alternat Med. 2007;4(3):327-33. https://doi.org/10.1093/ecam/nel093
  83. Hobbs AJ, Higgs A, Moncada S. Inhibition of nitric oxide synthase as a potential therapeutic target. Annu Rev Pharmacol Toxicol. 1999; 39:191-220. https://doi.org/10.1146/annurev.pharmtox.39.1.191
  84. Korhonen R et al. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005; 4(4):471-9. https://doi.org/10.2174/1568010054526359
  85. Lee AK et al. Inhibition of lipopolysaccharide -inducible nitric oxide synthase, TNF -alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation. Br J Pharmacol. 2003; 139(1):11-20. https://doi.org/10.1038/sj.bjp.0705231
  86. Delgado AV, McManus AT, Chambers JP. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin 2, and interleukin 6 by rat leukocyte subpopulations after exposure to substance P. Neuropeptides. 2003; 37(6):355-61. https://doi.org/10.1016/j.npep.2003.09.005
  87. Chen Y et al. CpG DNA induces cyclooxygenase-2 expression and prostaglandin production. Int Immunol. 2001;13(8):1013-20. https://doi.org/10.1093/intimm/13.8.1013
  88. Minamida K et al. Effects of ingestion of difructose anhydride III(DFA III) and the DFA III-assimilating bacterium Ruminococcus productus on rat intestine. Biosci Biotechnol Biochem. 2006;70(2):332-29. https://doi.org/10.1271/bbb.70.332
  89. Chandler RL. Experimental bacterial mastitis in the mouse. J Med Microbiol. 1970;3(2):273-82. https://doi.org/10.1099/00222615-3-2-273
  90. Xu XL et al. Mannose prevents lipopolysaccharide-induced acute lung injury in rats. Inflamm Res. 2008; 57(3):104-10. https://doi.org/10.1007/s00011-007-7037-y
  91. Wang Y, Marsden PA. Nitric oxide synthases: gene structure and regulation. Adv Pharmacol. 1995;34:71-90. https://doi.org/10.1016/S1054-3589(08)61081-9