The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
권호 표지
DOI QR코드

DOI QR Code

Effect of Haegan-jeon on Thioacetamide-Induced Liver Fibrosis

해간전(解肝煎)이 Thioacetamide로 유발된 간섬유화에 미치는 영향

  • Choi, Jeong Won (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Kim, Gun Woo (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Shin, Mi-Rae (Dept. of Herbology, College of Korean Medicine, Daegu Haany University) ;
  • Roh, Seong-Soo (Dept. of Herbology, College of Korean Medicine, Daegu Haany University)
  • 최정원 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 김건우 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 신미래 (대구한의대학교 한의과대학 본초약리학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2022.09.05
  • Accepted : 2022.10.04
  • Published : 2022.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: To investigate the protective effects of Haeganjeon on a thioacetamide (TAA)-induced liver fibrosis mouse model and to determine the Haegan-jeon signaling pathway. Methods: Mice were randomly divided into 4 groups: Normal group (Nor), TAA-induced liver fibrosis group (Con), TAA-induced liver fibrosis group administered 50 mg/kg silymarin (S50), TAA-induced liver fibrosis group administered 200 mg/kg Haegan-jeon (H200). The liver fibrosis mouse model was established by intraperitoneal injection with TAA three times a week for 8 weeks. During the 8 weeks, mice were orally administered silymarin and Haegan-jeon every day. At the end of the study, serum was collected to measure the levels of AST, ALT, ammonia, and myeloperoxidase (MPO). Liver tissue was harvested and analyzed by western blotting and Masson's trichrome staining. Results: Administration of Haegan-jeon suppressed the increase in serum levels of AST, ALT, ammonia, and MPO due to TAA-induced liver fibrosis. Compared to the Con group, the H200 group showed increases in antioxidant-related factors (Nrf2, HO-1, catalase, and GPx-1/2) and decreases in inflammatory-related factors (NF-κB p65, p-IκB-α, Cox-2, iNOS, TNF-α, and IL-1β) in western blots. The H200 treatment inhibited the expression of α-SMA and Collagen I. Conclusions: Haegan-jeon showed a hepatoprotective effect induced by activation of antioxidant-related factors, such as Nrf2, and it regulated the inflammation response by suppression of NF-κB.

Keywords

Acknowledgement

본 성과물은 2022년도 정부(과학기술정보통신부)의 재원으로 한국연구재단(No. 2018R1A5A2025272)의 지원에 의해 수행되었습니다.

References

  1. Kim HY. Effects of Water Extracts of Black Tea on Hepatic Functional Improvement and Anti-fibrosis in Rats. J East Asian Soc Dietary Life 2013;23(1):44-52.
  2. Lee HS, Koo YC, Lee KW. Suppressive Activity of Extract of Termialia chebula Retz. On Hepatic Fibrosis. Korean J Food Sci Techonl 2009;5(41):597-601.
  3. Wang R, Song F, Li S, Wu B, Gu Y, Yuan Y. Salvianolic acid A attenuates CCl4-induced liver fibrosis by regulating the PI3K/AKT/mTOR, Bcl-2/Bax and caspase-3/cleaved caspase-3 signaling pathways. Drug Des Devel Ther 2019;13:1889-900. https://doi.org/10.2147/DDDT.S194787
  4. Kim SY, Kim SJ, Choi YJ, Yu KY, Chung CH, Shim JS. Analysis of Active Components in Cirsium japonicum var. ussuriense Extracts and Their Effect on TGF-beta Induced Hepatic Stellate Cells Activation. Kor J Pharmacogn 2013;44(2):110-7.
  5. El-Gendy ZA, El-Marasy SA, Ahmed RF, El-Batran SA, Abd El-Rahman SS, Ramadan A, et al. Hepatoprotective effect of Saccharomyces Cervisciae Cell Wall Extract against thioacetamide-induced liver fibrosis in rats. Heliyon 2021;7(6):e07159. https://doi.org/10.1016/j.heliyon.2021.e07159
  6. Liu Y, Meyer C, Xu C, Weng H, Hellerbrand C, ten Dijke P, et al. Animal models of chronic liver disease. Am J Physiol Gastrointest Liver Physiol 2013;304(5):G449-68. https://doi.org/10.1152/ajpgi.00199.2012
  7. Perez Tamayo R. Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis? Hepatology 1983;3(1):112-20.
  8. Lee JA, Shin MR, Lee JH, Park HJ, Roh SS. The Effect of Chaenomelis Fructus on Thioacetamide -Induced Acute Hepatic injury. J Korean Soc Food Sci Nutr 2021;50(4):332-29.
  9. El-Baz FK, Salama A, Ali SI, Elgohary R. Haematococcus pluvialis Carotenoids Enrich Fractions Ameliorate Liver Fibrosis Induced by Thioacetamide in Rats: Modulation of Metalloproteinase and Its Inhibitor. Biomed Res Int 2021;2021:6631415.
  10. Hwang TW, Sim HC, Kim SB, Yoo SK, Cho HB. Effects of Haeganjeon on Immobilization-Stress or Cold-Stress in Mice. J Orient Gynecol 2005;18(3):51-66.
  11. Kim JK, Jung JY, Park SM, Park JA, Ku SK, Byun SH, et al. Study of hepatoprotective effect of Haegan-jeon through activation of nuclear factor erythroid 2-related factor 2 and optimization of herbal composition based on molecular mechanism. Herb Formula Sci 2018;26(3):207-21.
  12. Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 1965;16:144-58. https://doi.org/10.5344/ajev.1965.16.3.144
  13. Jiao H, Wang SY. Correlation of antioxidant capacities to oxygen radical scavenging enzyme activities in blackberry. J Agric Food Chem 2000;48(11):5672-6. https://doi.org/10.1021/jf000765q
  14. Blois MS. Antioxidant determinations by the use of a stable free radical. Nature 1958;181:1199-200. https://doi.org/10.1038/1811199a0
  15. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biol Med 1999;26(9-10):1231-7. https://doi.org/10.1016/S0891-5849(98)00315-3
  16. Choi JW, Shin MR, Lee JH, Roh SS. Hepatoprotective Effect of Uncaria rhynchophylla on Thioacetamide -Induced Liver Fibrosis Model. Biomed Sci Lett 2021;27(3):142-53. https://doi.org/10.15616/BSL.2021.27.3.142
  17. Abenavoli L, Izzo AA, Milic N, Cicala C, Santini A, Capasso R. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. Phytother Res 2018;32(11):2202-13. https://doi.org/10.1002/ptr.6171
  18. Gillessen A, Schmidt HH. Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review. Adv Ther 2020;37(4):1279-301. https://doi.org/10.1007/s12325-020-01251-y
  19. Ahn BT, Kim JD, Moon JY. Antioxidative and Protective Effects of Haeganjeon Extract on Oxidative Damage of Hepatocytes. Herbal formula science 2002;10(2):127-41.
  20. Pientaweeratch S, Panapisal V, Tansirikongkol A. Antioxidant, anti-collagenase and anti-elastase activities of Phyllanthus emblica, Manilkara zapota and silymarin: an in vitro comparative study for anti-aging applications. Pharm Biol 2016;54(9):1865-72. https://doi.org/10.3109/13880209.2015.1133658
  21. Kim HJ, Kim SY, Shin SP, Yang YJ, Bang CS, Baik GH, et al. Immunological measurement of aspartate/alanine aminotransferase in predicting liver fibrosis and inflammation. Korean J Intern Med 2020;35(2):320-30. https://doi.org/10.3904/kjim.2018.214
  22. De Chiara F, Thomsen KL, Habtesion A, Jones H, Davies N, Gracia-Sancho J, et al. Ammonia Scavenging Prevents Progression of Fibrosis in Experimental Nonalcoholic Fatty Liver Disease. Hepatology 2020;71(3):874-92. https://doi.org/10.1002/hep.30890
  23. Li JP, Gao Y, Chu SF, Zhang Z, Xia CY, Mou Z, et al. Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis. Acta Pharmacol Sin 2014;35(8):1031-44. https://doi.org/10.1038/aps.2014.41
  24. de Souza Basso B, Haute GV, Ortega-Ribera M, Luft C, Antunes GL, Bastos MS, et al. Methoxyeugenol deactivates hepatic stellate cells and attenuates liver fibrosis and inflammation through a PPAR-γ and NF-kB mechanism. J Ethnopharmacol 2021;280:114433. https://doi.org/10.1016/j.jep.2021.114433
  25. Abdel-Rahman RF, Fayed HM, Asaad GF, Ogaly HA, Hessin AF, Salama AAA, et al. The involvement of TGF-β1 /FAK/α-SMA pathway in the antifibrotic impact of rice bran oil on thioacetamide-induced liver fibrosis in rats. PLoS One 2021;16(12):e0260130. https://doi.org/10.1371/journal.pone.0260130
  26. Jia Q, Cao H, Shen D, Li S, Yan L, Chen C, et al. Quercetin protects against atherosclerosis by regulating the expression of PCSK9, CD36, PPARγ, LXRα and ABCA1. Int J Mol Med 2019;44(3):893-902.