DOI QR코드

DOI QR Code

Inhibitory Effects of Cheongpochukeo-tang on LPS-induced Inflammation Model

LPS로 유도된 염증모델에 대한 청포축어탕의 억제 효과

  • Hong, Ka-Kyung (Dept. of OB&GY, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Soo-Hyung (Dept. of OB&GY, College of Oriental Medicine, Wonkwang University) ;
  • Jung, Hyun-Tae (Dept. of OB&GY, College of Oriental Medicine, Wonkwang University) ;
  • Kim, Song-Baek (Dept. of OB&GY, College of Oriental Medicine, Wonkwang University)
  • 홍가경 (원광대학교 한의과대학 한방부인과학교실) ;
  • 이수형 (원광대학교 한의과대학 한방부인과학교실) ;
  • 정현태 (원광대학교 한의과대학 한방부인과학교실) ;
  • 김송백 (원광대학교 한의과대학 한방부인과학교실)
  • Received : 2021.10.08
  • Accepted : 2021.11.26
  • Published : 2021.11.26

Abstract

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

Keywords

References

  1. Kumar V, et al. Robbins basic pathology 8th rev. ed. Seoul:Epublic. 2009:31-5, 57-8.
  2. Male D, Brostoff J, Gray A. Immunology. London:Mosby. 1998:61-9, 229-32.
  3. Korean Society of Obstetrics and Gynecology. Gynecology. 5th rev. ed. Seoul:Korea Medical Book Publishing Company. 2015:154, 546.
  4. The society of Korean medicine obstetrics and gynecology. Korean medicine obstetrics and gynecology. 3rd rev. ed. Seoul: Euiseongdang. 2016:164, 171, 331-42.
  5. Tsevat DG, et al. Sexually transmitted diseases and infertility. American journal of obstetrics and gynecology. 2017;216(1):1-9. https://doi.org/10.1016/j.ajog.2016.08.008
  6. Kyunghee university Korean medicine hospital. Hanbangjejehaeseoljip(韓方製劑解說集(全)). Seoul:Kyunghee university medicine center. 1983:134.
  7. Gang SH, Choi SH, Ahn KS. Experimental studies on effects of Qingbaozhuyutang(淸胞逐瘀湯), bee veenom on the blood stasis pattern. The journal of Korean oriental medicine society. 1995;16(1):351-69.
  8. Lee KS, Song BK. Clinical observation on Cheongpochookeo-tang. The Journal Of Oriental Obstetrics & Gynecology. 1987;1(1):33-7.
  9. Wee HS, et al. Pregnancy of infertility with endometriosis after oriental medicine treatment diagnosed as a IVF case. A case report. The Journal Of Oriental Obstetrics & Gynecology. 2010;23(3):213-20.
  10. Cho SH, Jin CS. The clinical study of PID patient by oriental medical treatment(focused on herbal medication & retention enema). The Journal of Oriental Obstetrics & Gynecology. 2002;15(3):181-9.
  11. Ban HR, Lee JA, Cho SH. A case of chronic pelvic inflammatory disease. The Journal of Oriental Obstetrics & Gynecology. 2005;18(1):253-61.
  12. Song YR, et al. The clinical study one pelvic inflammatory disease(PID) patient treatments by Korean medicine. The Journal of Oriental Obstetrics & Gynecology.2014;27(3):158-67. https://doi.org/10.15204/jkobgy.2014.27.3.158
  13. Chung JH, Song BK. Effects of Kyokhach'ugotang and Ch'onp'och'ugotang on anti-inflammatory, antipyretic, analgesic, anti-microbial and anti-thrombose action. Kyunghee Univ. Theses collection. 1986;15:101-16.
  14. Kim DH, et al. Rubi Fructus Water Extract Alleviates LPS-Stimulated Macrophage Activation via an ER Stress-Induced Calcium/CHOP Signaling Pathway. Nutrients. 2020;12(11):3577. https://doi.org/10.3390/nu12113577
  15. Wu C, et al. Neocryptotanshinone inhibits lipopolysaccharide-induced inflammation in RAW264.7 macrophages by suppression of NF-κB and iNOS signaling pathways. Acta Pharmaceutica Sinica B. 2015;5(4):323-9. https://doi.org/10.1016/j.apsb.2015.01.010
  16. Kim YH, et al. Biological Properties of Vibrio vulnificus Lipopolysaccharide and compared to those of Escherichia coli and Salmonella typhimurium Lipopolysaccharides. Korean journal of microbiology. 1989;27(2):147-54.
  17. Tateda K, et al. Lipopolysaccharide-induced lethality and cytokine production in aged mice. Infect Immun. 1996;64(3):769-74. https://doi.org/10.1128/iai.64.3.769-774.1996
  18. Patel S, et al. RIP1 inhibition blocks inflammatory diseases but not tumor growth or metastases. Cell Death & Differentiation, 2020;27(1):161-75. https://doi.org/10.1038/s41418-019-0347-0
  19. Yun YG. Donguibangje and Cheobanghaeseol(東醫方劑와 處方解說). 4th rev. ed. Seoul: Euiseongdang. 2011:288-9.
  20. Yun HJ, et al. Inhibitory effect of Coicis semen extract(CSE) on pro-inflammatory mediatory. The Journal of Pediatrics of Korean Medicine. 2009;23(1):159-71.
  21. Ryu IH, et al. Effects of Patrinia scabiosaefolia aqueous extract on cytokine and NF-κB activation in LPS-induced RAW 264.7 cells and mouse. The Journal of Oriental Obstetrics & Gynecology. 2017;30(2):1-15. https://doi.org/10.15204/jkobgy.2017.30.1.001
  22. Lee EJ, et al. Inhibition of LPS-induced inflammatory biomarkers by ethyl acetate fraction of Patrinia scabiosaefolia through suppression of NF- κB activation in RAW 264.7 cells. Immunopharmacology and Immunotoxicology. 2012;34(2):282-91. https://doi.org/10.3109/08923973.2011.602412
  23. Kim M, et al. The anti-inflammatory effect of Achyranthes japonica on lipopolysaccharide-induced inflammatory activity in murine macrophages. The Korea Journal of Herbology. 2011;26(2):51-7. https://doi.org/10.6116/KJH.2011.26.2.051
  24. Chung WS. The anti-inflammatory effects of Achyranthes japonica. Department of Medicine, Graduate school of Wonkwang university. 2011.
  25. Lee D, et al. Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase, TNF- α, IL-1β and COX-2 Expression by Flower and Whole Plant of Lonicera japonica. Journal of Physiology & Pathology in Korean Medicine. 2005;19(2):481-9.
  26. Yun YG, et al. Inhibitory Effect of Aqueous Extract from Lonicera japonica Flower on LPS-induced Inflammatory Mediators in RAW 264.7 Macrophages. The Korea Journal of Herbology. 2007;22(3):117-25.
  27. Chae KW. Anti-inflammatory activity and osteoclast formation effects of Lonicerae Flos. Department of Herbology, Graduate school of Kyunghee university. 2008.
  28. Yun KJ, Lee EY. Effects of hot aqueous and ethanol extract from Lonicera japonica Flos on NO and PGE2 in macrophage. Journal of Korean Acupuncture & Moxibustion Society. 2012;29(1):67-74.
  29. Ryu HK, et al. Research of the Anti-inflammatory Effects of Forsythiae Fructus and Lonicerae Flos Ethanol Extracts. The Journal of Korean Obstetrics and Gynecology. 2020;33(3):40-59. https://doi.org/10.15204/JKOBGY.2020.33.3.040
  30. Choi CM, et al. Analysis of Korean traditional medicinal treatment trend of infertility and development of questionnaire for infertility treatment. The Journal of Oriental Obstetrics & Gynecology. 2016;29(2):29-46. https://doi.org/10.15204/jkobgy.2016.29.2.029
  31. Westrom L, et al. Pelvic inflammatory disease and fertility. A cohort study of 1,844 women with laparoscopically verified disease and 657 control women with normal laparoscopic results. Sex Transm Dis. 1992;19(4):185-92. https://doi.org/10.1097/00007435-199207000-00001
  32. Grodstein F, Goldman MB, Cramer DW. Relation of tubal infertility to history of sexually transmitted diseases. American journal of epidemiology. 1993;137(5):577-84. https://doi.org/10.1093/oxfordjournals.aje.a116711
  33. Joeng JE, et al. In: Research proposal on the clinical cause and support plan of infertility. Ilsan:NHIS Ilsan Hospital Institute of Health Insurance & Clinical Research. 2017:51.
  34. Tsan MF, Gao B. Pathogen-associated molecular pattern contamination as putative endogenous ligands of Toll-like receptors. Journal of endotoxin research. 2007;13(1):6-14. https://doi.org/10.1177/0968051907078604
  35. Sharma JN, Al-Omran A, Parvathy S.S. Role of nitric oxide in inflammatory diseases. Inflammopharmacology. 2007;15(6):252-9. https://doi.org/10.1007/s10787-007-0013-x
  36. Spiller F, et al. Targeting nitric oxide as a key modulator of sepsis, arthritis and pain. Nitric Oxide. 2019;89(1):32-40. https://doi.org/10.1016/j.niox.2019.04.011
  37. Boveris A, Alvarez S, Navarro A. The role of mitochondrial nitric oxide synthase in inflammation and septic shock. Free radical biology and medicine. 2002;33(9):1186-93. https://doi.org/10.1016/S0891-5849(02)01009-2
  38. Tewari D, et al. Role of Nitric oxide in neurodegeneration: Function, regulation and inhibition. Curr Neuropharmacol. 2020;18(1):1-13. https://doi.org/10.2174/1570159x1801191216143152
  39. Kishimoto T, et al. Interleukin-6 family of cytokines and gp130. Blood. 1995;86(4):1243-54. https://doi.org/10.1182/blood.v86.4.1243.bloodjournal8641243
  40. Loeffler S, et al. Interleukin-6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1. International journal of cancer. 2005;115(2):202-13. https://doi.org/10.1002/ijc.20871
  41. John MAS, et al. Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Archives of Otolaryngology-Head & Neck Surgery. 2004;130(8):929-35. https://doi.org/10.1001/archotol.130.8.929
  42. Kotowicz B, et al. The value of tumor marker and cytokine analysis for the assessment of regional lymph node status in cervical cancer patients. International Journal of Gynecologic Cancer. 2008;18(6):1279-84. https://doi.org/10.1111/j.1525-1438.2007.01176.x
  43. Jones SA, Brendan JJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nature Reviews Immunology. 2018;18(12):773-89. https://doi.org/10.1038/s41577-018-0066-7
  44. Abul K, et al. Cellular and molecular immunology 7th rev. ed. Seoul: Panmuneducation. 2013:84-9, 180-6.
  45. Ren K, Torres R. Role of interleukin-1β during pain and inflammation. Brain research reviews. 2009;60(1):57-64. https://doi.org/10.1016/j.brainresrev.2008.12.020
  46. Borrelli E, et al. Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk. Critical care medicine. 1996;24(3):392-7. https://doi.org/10.1097/00003246-199603000-00006
  47. Ramseyer VD, Garvin JL. Tumor necrosis factor-α: regulation of renal function and blood pressure. American Journal of Physiology-Renal Physiology. 2013;304(10):1231-42.
  48. Cobb MH, Goldsmith EJ. Dimerization in MAP-kinase signaling. Trends Biochem Sci. 2000;25(1):7-9. https://doi.org/10.1016/S0968-0004(99)01508-X
  49. Cargnello M, Philippe PR. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiology and molecular biology reviews. 2011;75(1):50-83. https://doi.org/10.1128/MMBR.00031-10
  50. Lee AK, et al. Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappa B alpha phosphorylation, C/EBP and AP-1 activation. Br J Pharmacol. 2003;139(1):11-2. https://doi.org/10.1038/sj.bjp.0705231
  51. Baeuerle PA. I kappa B-NF-kappa B structures: at the interface of inflammation control. Cell. 1998;95(6):729-31. https://doi.org/10.1016/S0092-8674(00)81694-3
  52. Lee JE. Drug Delivery Systems - associated with Pediatric Endocrinology. Journal of Korean Society of Pediatric Endocrinology. 2011;16(1):7-12. https://doi.org/10.6065/jkspe.2011.16.1.7
  53. Turner PV, et al. Administration of substances to laboratory animals: routes of administration and factors to consider. Journal of the American Association for Laboratory Animal Science. 2011;50(5):600-13.
  54. Su GL. Lipopolysaccharides in liver injury: molecular mechanisms of Kupffer cell activation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2002;283(2):256-65.