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Protective effect of Artemisiae Capillaris Herba water extract on liver injury induced by thioacetamide

인진호 열수 추출물이 thioacetamide에 의해 유발된 간손상에 미치는 간보호 효과

  • Kim, Min Ju (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Lee, Jin A (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Shin, Mi-Rae (Department of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Park, Hae-Jin (DHU Bio Convergence Testing Center) ;
  • Roh, Seong-Soo (Department of Herbology, College of Korean Medicine, Daegu Haany University)
  • 김민주 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 이진아 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 박해진 (대구한의대학교 DHU 바이오융복합시험센터) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2021.03.29
  • Accepted : 2021.05.11
  • Published : 2021.08.31

Abstract

Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAA-induced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidant-related factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.

본 연구는 TAA 복강투여로 유발된 간 손상 동물모델에서 인진호 열수 추출물의 간보호 효능을 평가하였으며 다음과 같은 결론을 얻었다. TAA로 인해 줄어드는 체중은 인진호 열수 추출물을 투여한 군에서 유의하게 증가하였으며, 간손상에 의해 증가한 혈중 암모니아 함량과 MPO 활성은 인진호 열수 추출물 투여군에서 유의하게 감소하였다. 간 조직의 western blotting 결과, 인진호 열수 추출물 투여가 산화적 스트레스 관련 인자들의 발현을 유의적으로 감소시키고, 항산화 관련 인자들의 발현을 유의하게 증가시켰으며, MMPs의 발현은 감소시키고 TIMP-1의 발현은 증가시킴을 확인할 수 있었다. 따라서 인진호 열수 추출물은 TAA로 유발된 간손상 동물모델에서 항산화 작용을 통해 산화적 스트레스를 억제하여 간보호 효과를 보이는 것으로 판단된다.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2018R1A5A2025272).

References

  1. Park JY, Park CM, Kim JJ, Song YS. Hepatoprotective activity of Dandelion (Taraxacum officinale) water extract against D-galactosamine-induced hepatitis in rats. J Korean Soc Food Sci Nutr 2008; 37(2): 177-183. https://doi.org/10.3746/JKFN.2008.37.2.177
  2. Lee UE, Friedman SL. Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 2011; 25(2): 195-206. https://doi.org/10.1016/j.bpg.2011.02.005
  3. Ozdemir-Kumral ZN, Erkek BE, Karakus B, Almaci M, Fathi R, Yuksel M, et al. Potential effect of 1,25 Dihydroxyvitamin D3 on thioacetamide-induced hepatotoxicity in rats. J Surg Res 2019; 243: 165-172. https://doi.org/10.1016/j.jss.2019.05.020
  4. Han JM, Kim HG, Choi MK, Lee JS, Lee JS, Wang JH, et al. Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats. Exp Toxicol Pathol 2013; 65(6): 837-844. https://doi.org/10.1016/j.etp.2012.12.002
  5. Kim JS, Kim KL. Anti-oxidative and anti-inflammatory effects of Artemisiae Capillaris Extract. Korean J Aesthet Cosmetol 2015; 13(6): 805-812.
  6. Ham I, Jung SW, Lee KJ, Park KH, Choi HY. Effect of the aerial part of Artemisia capillaris, and A. iwayomogi on the hyperlipidemia of rats induced by Triton WR-1339. Korea J Herbol 2005; 20(1): 45-52.
  7. Kim HT, Kim JW, Lim MK, Jin TW, Yeo SG, Jang KH, et al. Cytotoxic effect of Artemisia capillaris extracts on the cancer cells on in vitro. J Vet Clin 2007; 24(3): 367-371.
  8. Yu F, Qian H, Zhang J, Sun J, Ma Z. Simultaneous quantification of eight organic acid components in Artemisia capillaris Thunb (Yinchen) extract using high-performance liquid chromatography coupled with diode array detection and high-resolution mass spectrometry. J Food Drug Anal 2018; 26(2): 788-795. https://doi.org/10.1016/j.jfda.2017.04.003
  9. Kim KS, Yang HJ, Lee JY, Na YC, Kwon SY, Kim YC, et al. Effects of β-sitosterol derived from Artemisia capillaris on the activated human hepatic stellate cells and dimethylnitrosamine-induced mouse liver fibrosis. BMC Complement Altern Med 2014; 14(1): 363-372. https://doi.org/10.1186/1472-6882-14-363
  10. Lee SH, Lee JY, Kwon YI, Jang HD. Anti-osteoclastic activity of Artemisia capillaris Thunb. extract depends upon attenuation of osteoclast differentiation and bone tesorption-associated acidification due to chlorogenic acid, hyperoside, and scoparone. Int J Mol Sci 2017; 18(2): 322-335. https://doi.org/10.3390/ijms18020322
  11. Kwon H, Jung JW, Lee YC, Ryu JH, Kim DH. Neuroprotective effect of the ethanol extract of Artemisia capillaris on transient forebrain ischemia in mice via nicotinic cholinergic receptor. Chin J Nat Med 2018; 16(6): 428-435.
  12. Luo M, Dong L, Li J, Wang Y, Shang B. Protective effects of pentoxifylline on acute liver injury induced by thioacetamide in rats. Int J Clin Exp Pathol 2015; 8(8): 8990-8996.
  13. El Awdan SA, Amin MM, Hassan A. Cilostazol attenuates indices of liver damage induced by thioacetamide in albino rats through regulating inflammatory cytokines and apoptotic biomarkers. Eur J Pharmacol 2018; 822: 168-176. https://doi.org/10.1016/j.ejphar.2018.01.021
  14. Kim KJ, Shin MR, Kim SH, Kim SJ, Lee AR, Kwon O, et al. Protective effect of Tongyuhwalhyeol-tang on liver injury in thioacetamide-induced rat. Korea J Herbol 2018; 33(1): 37-46. https://doi.org/10.6116/kjh.2018.33.1.37
  15. Brusilow SW. Hyperammonemic encephalopathy. Medicine (Baltimore) 2002; 81(3): 240-249. https://doi.org/10.1097/00005792-200205000-00007
  16. De Minicis S, Bataller R, Brenner DA. NADPH oxidase in the liver: defensive, offensive, or fibrogenic? Gastroenterology 2006; 131(1): 272-275. https://doi.org/10.1053/j.gastro.2006.05.048
  17. Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD. Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 2001; 269(1-2): 131-140. https://doi.org/10.1016/S0378-1119(01)00449-8
  18. Paik YH, Kim J, Aoyama T, De Minicis S, Bataller R, Brenner DA. Role of NADPH oxidases in liver fibrosis. Antioxid Redox Signal 2014; 20(17): 2854-2872. https://doi.org/10.1089/ars.2013.5619
  19. Kasai S, Shimizu S, Tatara Y, Mimura J, Itoh K. Regulation of Nrf2 by mitochondrial reactive oxygen species in physiology and pathology. Biomolecules 2020; 10(2): 320-340. https://doi.org/10.3390/biom10020320
  20. Lee JA, Park HJ, Kim SH, Kim MJ, Kim KJ, Shin MR, et al. Evaluation of Evodiae Fructus extract on the chronic acid reflux esophagitis in rats. Korea J Herbol 2019; 34(2): 15-23. https://doi.org/10.6116/KJH.2019.34.2.15
  21. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 2010; 141(1): 52-67. https://doi.org/10.1016/j.cell.2010.03.015
  22. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 2003; 92(8): 827-839. https://doi.org/10.1161/01.RES.0000070112.80711.3D
  23. Naim A, Pan Q, Baig MS. Matrix metalloproteinases (MMPs) in liver diseases. J Clin Exp Hepatol 2017; 7(4): 367-372. https://doi.org/10.1016/j.jceh.2017.09.004