Journal of Convergence Korean Medicine (대한융합한의학회지)

Academy of Convergence Korean Medicine (대한융합한의학회)
권호 표지

Effect of Water Extract of Aconiti Lateralis Preparata Radix on Lung Injury in LPS-induced Septic C57BL6 Mice

부자 추출물이 LPS로 유도된 C57BL6 마우스의 패혈증 연관 급성 폐 손상에 미치는 영향

  • In-Seung Lee (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Mina Boo (Department of Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Jae Ouk Sim (Department of Pharmacology, College of Korean Medicine, Kyung Hee University) ;
  • Seung-Ho Baek (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Jinbong Park (Department of Pharmacology, College of Korean Medicine, Kyung Hee University)
  • 이인승 (동국대학교 한의과대학 병리학교실) ;
  • 부민아 (경희대학교 한의과대학 약리학교실) ;
  • 심재욱 (경희대학교 한의과대학 약리학교실) ;
  • 백승호 (동국대학교 한의과대학 병리학교실) ;
  • 박진봉 (경희대학교 한의과대학 약리학교실)
  • Received : 2022.12.06
  • Accepted : 2022.12.26
  • Published : 2022.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: TSepsis and subsequent acute lung injury (ALI) is a critical state of health caused by infection or endotoxins. This study was conducted to evaluate the effect of Water Extract of Aconiti Lateralis Preparata Radix (AR) on lipopolysaccharide (LPS)-induced sepsis in C57BL/6 mice. Methods: Male C57BL/6 mice were intraperitoneally injected with LPS to induce sepsis and ALI. AR was orally fed twice at 30 min and 180 min after LPS injection. At 24 h post injection, mice were sacrificed, bronchoalveolar lavage fluid (BALF) and blood was collected, and lung tissue was harvested. Hematoxylin and eosin staining was performed in lung tissues, wet/dry ratio of the lung tissue was measured, and the serum cytokine and chemokine levels were analyzed. Results: AR revoked the LPS-induced pathological changes in lung tissues, such as abnormal histological structures, immune cell infiltration and lung edema. Also, AR suppressed the neutrophil infiltration into the lung which was greatly increased by LPS injection based on the cell content of collected BALF. Serum cytokines and chemokines were measured, and AR reversed the LPS-induced increase of cytokines such as interleukin 1 beta, interleukin 6, tumor necrosis factor alpha and chemokines including C-X-C motif chemokine ligand 1 and 2. Conclusion: TAR showed a protective effect in the pathological progress of LPS-induced ALI. Especially, AR suppressed lung edema and infiltration of neutrophils by inhibiting cytokine and chemokine expressions. Such results demonstrate the potential of AR as a therapeutic agent for sepsis and sepsis-induced ALI.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (grant no. NRF-2020R1C1C1009721, NRF-2020R1I1A3063625 and NRF-2022R1I1A3073095).

References

  1. Fleischmann C, Scherag A, Adhikari NK, Hartog CS, Tsaganos T, Schlattmann P, Angus DC, Reinhart K. Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2016;193(3):259-72.  https://doi.org/10.1164/rccm.201504-0781OC
  2. Rossaint J, Zarbock A. Pathogenesis of Multiple Organ Failure in Sepsis. Crit Rev Immunol. 2015;35(4):277-91.  https://doi.org/10.1615/CritRevImmunol.2015015461
  3. Varisco BM. The pharmacology of acute lung injury in sepsis. Adv Pharmacol Sci. 2011;2011:254619. 
  4. Lewis AJ, Seymour CW, Rosengart MR. Current Murine Models of Sepsis. Surg Infect (Larchmt). 2016;17(4):385-93.  https://doi.org/10.1089/sur.2016.021
  5. OASIS: Oriental Medicine Advanced Searching Integrated System [Internet]. [cited Nov 13, 2022]. Available from: https://oasis.kiom.re.kr/.  
  6. Korean Pharmacopeia. 11 ed2019. 
  7. Yoon S, Kim H. Donguibogam. Seoul: Donguibogam Publishing Company. 2006:297-2189. 
  8. Hotchkiss RS, Moldawer LL, Opal SM, Reinhart K, Turnbull IR, Vincent JL. Sepsis and septic shock. Nat Rev Dis Primers. 2016;2:16045. 
  9. Prest J, Sathananthan M, Jeganathan N. Current Trends in Sepsis-Related Mortality in the United States. Crit Care Med. 2021;49(8):1276-84.  https://doi.org/10.1097/CCM.0000000000005017
  10. 김성남, 박현정, 이형민, 임채만, 오동규, 서지영. 국내 패혈증 환자 관리 개선을 위한 심층조사 결과 (1 차년도). 주간 건강과 질병. 2020;13(37):2750-60. 
  11. Wiersinga WJ, van der Poll T. Immunopathophysiology of human sepsis. EBioMedicine. 2022:104363. 
  12. Vermassen J, Decruyenaere J, De Bus L, Depuydt P, Colpaert K. Characteristics of Sepsis-2 septic shock patients failing to satisfy the Sepsis-3 septic shock definition: an analysis of real-time collected data. Ann Intensive Care. 2021;11(1):154. 
  13. Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 Update. Crit Care Med. 2018;46(6):997-1000.  https://doi.org/10.1097/CCM.0000000000003119
  14. 정원익, 김준성, 유재형, 강진영, 유지나, 조연주, 정성민, 김원영, 유승목. 패혈증 쇼크 환자의 1시간 묶음 치료가 사망률에 미치는 영향. 대한응급의학회지. 2019;30(6):537-44. 
  15. Jiebin Z. Jingyuequanshu (景岳全書). 
  16. Ning L, Rui X, Guorui L, Tinglv F, Donghang L, Chenzhen X, Xiaojing W, Qing G. A novel mechanism for the protection against acute lung injury by melatonin: mitochondrial quality control of lung epithelial cells is preserved through SIRT3-dependent deacetylation of SOD2. Cell Mol Life Sci. 2022;79(12):610.  https://doi.org/10.1007/s00018-022-04628-0
  17. Tang W, Tang R, Zhao Y, Peng J, Wang D. Comparison of Clinical Characteristics and Predictors of Mortality between Direct and Indirect ARDS. Medicina (Kaunas). 2022;58(11). 
  18. Gu J, Ran X, Deng J, Zhang A, Peng G, Du J, Wen D, Jiang B, Xia F. Glycyrrhizin alleviates sepsis-induced acute respiratory distress syndrome via suppressing of HMGB1/TLR9 pathways and neutrophils extracellular traps formation. Int Immunopharmacol. 2022;108:108730.  https://doi.org/10.1016/j.intimp.2022.108730
  19. Chaudhry H, Zhou J, Zhong Y, Ali MM, McGuire F, Nagarkatti PS, Nagarkatti M. Role of cytokines as a double-edged sword in sepsis. In Vivo. 2013;27(6):669-84. 
  20. Mera S, Tatulescu D, Cismaru C, Bondor C, Slavcovici A, Zanc V, Carstina D, Oltean M. Multiplex cytokine profiling in patients with sepsis. Apmis. 2011;119(2):155-63.  https://doi.org/10.1111/j.1600-0463.2010.02705.x
  21. Gouel-Cheron A, Allaouchiche B, Guignant C, Davin F, Floccard B, Monneret G. Early interleukin-6 and slope of monocyte human leukocyte antigen-DR: a powerful association to predict the development of sepsis after major trauma. PLoS One. 2012;7(3):e33095.  https://doi.org/10.1371/journal.pone.0033095
  22. Kumar AT, Sudhir U, Punith K, Kumar R, Ravi Kumar VN, Rao MY. Cytokine profile in elderly patients with sepsis. Indian J Crit Care Med. 2009;13(2):74-8.  https://doi.org/10.4103/0972-5229.56052
  23. Le J, Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987;56(3):234-48. 
  24. Schroder JM, Persoon NL, Christophers E. Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. J Exp Med. 1990;171(4):1091-100.  https://doi.org/10.1084/jem.171.4.1091
  25. Cummings CJ, Martin TR, Frevert CW, Quan JM, Wong VA, Mongovin SM, Hagen TR, Steinberg KP, Goodman RB. Expression and function of the chemokine receptors CXCR1 and CXCR2 in sepsis. J Immunol. 1999;162(4):2341-6.  https://doi.org/10.4049/jimmunol.162.4.2341
  26. Al-Alwan LA, Chang Y, Mogas A, Halayko AJ, Baglole CJ, Martin JG, Rousseau S, Eidelman DH, Hamid Q. Differential roles of CXCL2 and CXCL3 and their receptors in regulating normal and asthmatic airway smooth muscle cell migration. J Immunol. 2013;191(5):2731-41. https://doi.org/10.4049/jimmunol.1203421