대한한의학방제학회지 (Herbal Formula Science)

  • 제31권1호
  • /
  • Pages.53-65
  • /
  • 2023
  • /
  • 1229-1218(pISSN)
  • /
  • 2288-5641(eISSN)
대한한의학방제학회 (The Korean Medicine Society for the Herbal Formula Study)
권호 표지
DOI QR코드

DOI QR Code

사염화탄소 유발 급성 간 손상에 대한 발효 오미자박 및 헛개과병 추출물의 혼합 비율에 따른 간 보호효능

Hepatoprotective effect of fermented Schizandrae Fructus Pomace extract and Hoveniae Semen Cum Fructus extract combination mixtures against carbon tetrachloride-induced acute liver injured mice

  • 박혜림 (뉴트라코어) ;
  • 제갈경환 (대구한의대학교 한의과대학 원전학교실) ;
  • 최범락 (뉴트라코어) ;
  • 김재광 (한국한의학연구원 한의기술응용센터) ;
  • 구세광 (대구한의대학교 한의과대학 해부조직학교실)
  • Hye-Rim, Park (Nutracore Co., Ltd) ;
  • Kyung Hwan, Jegal (Department of Korean Medical Classics, College of Korean Medicine, Daegu Haany University) ;
  • Beom-Rak, Choi (Nutracore Co., Ltd) ;
  • Jae Kwang, Kim (Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine) ;
  • Sae Kwang, Ku (Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University)
  • 투고 : 2023.02.03
  • 심사 : 2023.02.20
  • 발행 : 2023.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objectives : Present study investigated the hepatoprotective effects and the optimal mixing ratio of fermented Schizandrae Fructus Pomace (fSFP) and Hoveniae Semen Cum Fructus (HSCF) extract combination in carbon tetrachloride (CCl4)-induced acute liver injury mice. Methods : ICR mice were orally administered with 200 mg/kg of fSFP, HSCF and mixtures of fSFP and HSCF [MSH (w:w); 1:1, 1:2, 1:4, 1:6, 2:1, 4:1, 6:1, and 8:1] for 7 consecutive days. Silymarin (100 mg/kg) was administered as a reference drug. 0.5 mL/kg of CCl4 was injected intraperitoneally to induce acute liver injury. Body weight gain, relative liver weight, serum chemistry, histopathological analysis, and hepatic endogenous antioxidants capacities were observed. Results : All diverse combinations of MSH significantly reduced relative liver weight increase by CCl4. In addition, MSH administrations significantly decreased the elevation of serum alanine aminotransferase and aspartate aminotransferase activities by CCl4. Histopathological observation indicated that all MSH treatments significantly reduced the increase of degenerated hepatocytes, inflammatory cell infiltration, and histological activity index score by CCl4. Moreover, all MSH administrations reduced the elevation of malondialdehyde contents, and ameliorated the reduction of hepatic glutathione contents, superoxide dismutase activity, and catalase activity. Among the various mixing ratio of MSH combinations, MSH 1:1 and 2:1 showed the most potent anti-oxidative stress, and hepatoprotective effect. Conclusion : Present results suggest that 1:1 and 2:1 combinations of MSH is promising herbal formulation with the hepatoprotective effect against oxidative stress.

키워드

과제정보

본 연구는 2020년도 중소벤처기업부(과제번호: S2940975)의 기술개발사업 지원을 받아 수행되었으며 이에 감사드립니다.

참고문헌

  1. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363-83.  https://doi.org/10.1038/s41580-020-0230-3
  2. He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species. Cell Physiol Biochem. 2017;44(2):532-53.  https://doi.org/10.1159/000485089
  3. Gaschler MM, Stockwell BR. Lipid peroxidation in cell death. Biochem Biophys Res Commun. 2017;482(3):419-25.  https://doi.org/10.1016/j.bbrc.2016.10.086
  4. Cichoz-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014;20(25):8082-91.  https://doi.org/10.3748/wjg.v20.i25.8082
  5. Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol. 2001;35(2):297-306.  https://doi.org/10.1016/S0168-8278(01)00142-8
  6. Sakaguchi S, Takahashi S, Sasaki T, Kumagai T, Nagata K. Progression of alcoholic and non-alcoholic steatohepatitis: common metabolic aspects of innate immune system and oxidative stress. Drug Metab Pharmacokinet. 2011;26(1):30-46.  https://doi.org/10.2133/dmpk.DMPK-10-RV-087
  7. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, et al. The Role of Oxidative Stress and Antioxidants in Liver Diseases. Int J Mol Sci. 2015;16(11):26087-124.  https://doi.org/10.3390/ijms161125942
  8. Professors of herbology in colleges of Korean medicine. Herbology. Seoul:Yeonglimsa. 2004:685-737. 
  9. Szopa A, Ekiert R, Ekiert H. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: a review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem Rev. 2017;16(2):195-218.  https://doi.org/10.1007/s11101-016-9470-4
  10. Kopustinskiene DM, Bernatoniene J. Antioxidant Effects of Schisandra chinensis Fruits and Their Active Constituents. Antioxidants (Basel). 2021;10(4):620. 
  11. Park HJ, Lee SJ, Song Y, Jang SH, Ko YG, Kang SN, et al. Schisandra chinensis prevents alcohol-induced fatty liver disease in rats. J Med Food. 2014;17(1):103-10.  https://doi.org/10.1089/jmf.2013.2849
  12. Jang MK, Nam JS, Kim JH, Yun YR, Han CW, Kim BJ, et al. Schisandra chinensis extract ameliorates nonalcoholic fatty liver via inhibition of endoplasmic reticulum stress. J Ethnopharmacol. 2016;185:96-104.  https://doi.org/10.1016/j.jep.2016.03.021
  13. Seo YM, Kim HJ, Lee EJ, Chung CW, Sung HJ, Sohn HY, et al. Effects of Pomace of Schizandra chinensis, Schizandrin, and Gomisin A on LPS-induced Inflammatory Responses in RAW264.7 Cells. J Life Sci. 2018;28(3):339-44.  https://doi.org/10.5352/JLS.2018.28.3.339
  14. Kim MS, Sung HJ, Park JY, Sohn HY. Evaluation of Anti-oxidant, Anti-microbial and Anti-thrombosis Activities of Fruit, Seed and Pomace of Schizandra chinensis Baillon. J Life Sci. 2017;27(2):131-8.  https://doi.org/10.5352/JLS.2017.27.2.131
  15. Kim HJ, Seo YM, Lee EJ, Chung CW, Sung HJ, Sohn HY, et al. Anti-proliferative and Proapoptotic Activities by Pomace of Schisandra chinensis (Turcz.) Baill. and Schizandrin. J Life Sci. 2018;28(4):415-20.  https://doi.org/10.5352/JLS.2018.28.4.415
  16. Cho IJ, Kim JW, Jung JJ, Sung SH, Kim JK, Lee NJ, et al. Hepatoprotective effects of hoveniae semen cum fructus extracts in ethanol intoxicated mice. J Exerc Nutrition Biochem. 2016;20(1):49-64.  https://doi.org/10.20463/jenb.2016.03.20.1.4
  17. Kim YS, Park J, Kwon Y, Lim DW, Song M, Choi HY, et al. Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride. Kor J Herbology. 2013;28(4):25-32.  https://doi.org/10.6116/KJH.2013.28.4.25
  18. Hase K, Ohsugi M, Xiong Q, Basnet P, Kadota S, Namba T. Hepatoprotective effect of Hovenia dulcis THUNB. on experimental liver injuries induced by carbon tetrachloride or D-galactosamine/lipopolysaccharide. Biol Pharm Bull. 1997;20(4):381-5.  https://doi.org/10.1248/bpb.20.381
  19. Choi BR, Cho IJ, Jung SJ, Kim JK, Park SM, Lee DG, et al. Lemon balm and dandelion leaf extract synergistically alleviate ethanol-induced hepatotoxicity by enhancing antioxidant and anti-inflammatory activity. J Food Biochem. 2020;44(8):e13232.  https://doi.org/10.1111/jfbc.13376
  20. Choi B-R, Cho IJ, Jung S-J, Kim JK, Lee DG, Ku SK, et al. Study on the hepatoprotective effects of lemon balm and dandelion leaf extract combination in carbon tetrachloride-mediated liver injured mice. Herb Formular Sci. 2019;27(3):199-211. 
  21. Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696-9.  https://doi.org/10.1016/0168-8278(95)80226-6
  22. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25:192-205.  https://doi.org/10.1016/0003-2697(68)90092-4
  23. Sun Y, Larry WO, Ying L. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.  https://doi.org/10.1093/clinchem/34.3.497
  24. Chung W. The cost of liver disease in Korea: methodology, data, and evidence. Clin Mol Hepatol. 2015;21(1):14-21.  https://doi.org/10.3350/cmh.2015.21.1.14
  25. Scholten D, Trebicka J, Liedtke C, Weiskirchen R. The carbon tetrachloride model in mice. Lab Anim. 2015;49:4-11.  https://doi.org/10.1177/0023677215571192
  26. Zimmermann R, Flohe L, Weser U, Hartmann HJ. Inhibition of lipid peroxidation in isolated inner membrane of rat liver mitochondria by superoxide dismutase. Febs Letters. 1973;29:117-20.  https://doi.org/10.1016/0014-5793(73)80539-3
  27. Ighodaro OM, Akinloye OA. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid. Alex J Med. 2018;54(4):287-93.  https://doi.org/10.1016/j.ajme.2017.09.001
  28. Kang KS, Kim ID, Kwon RH, Lee JY, Kang JS, Ha BJ. The effects of fucoidan extracts on CCl(4)-induced liver injury. Arch Pharm Res. 2008;31(5):622-7.  https://doi.org/10.1007/s12272-001-1203-8
  29. Shin SM, Yang JH, Ki SH. Role of the Nrf2-ARE Pathway in Liver Diseases. Oxid Med Cell Longev. 2013;2013:763257. 
  30. Lee SB, Kim CY, Lee HJ, Yun JH, Nho CW. Induction of the phase II detoxification enzyme NQO1 in hepatocarcinoma cells by lignans from the fruit of Schisandra chinensis through nuclear accumulation of Nrf2. Planta Med. 2009;75(12):1314-8.  https://doi.org/10.1055/s-0029-1185685
  31. Shan Y, Jiang B, Yu J, Wang J, Wang X, Li H, et al. Protective Effect of Schisandra chinensis Polysaccharides Against the Immunological Liver Injury in Mice Based on Nrf2/ARE and TLR4/NF-κB Signaling Pathway. J Med Food. 2019;22(9):885-95.  https://doi.org/10.1089/jmf.2018.4377
  32. Chen Q, Zhang H, Cao Y, Li Y, Sun S, Zhang J, et al. Schisandrin B attenuates CCl4-induced liver fibrosis in rats by regulation of Nrf2-ARE and TGF-β/Smad signaling pathways. Drug Des Devel Ther. 2017;11:2179-91.  https://doi.org/10.2147/DDDT.S137507
  33. Zhao J, Ding K, Hou M, Li Y, Hou X, Dai W et al. Schisandra chinensis essential oil attenuates acetaminophen-induced liver injury through alleviating oxidative stress and activating autophagy. Pharm Biol. 2022;60(1):958-67.  https://doi.org/10.1080/13880209.2022.2067569
  34. Cho IJ, Kim JW, Jung JJ, Sung SH, Ku SK, Choi JS. In vitro protective effects of Hoveniae Semen cum Fructus extracts against oxidative stress. Toxicol Environ Health Sci. 2016;8:19-27.  https://doi.org/10.1007/s13530-016-0258-0
  35. Jeong MJ, Kim SR, Jung UJ. Schizandrin A supplementation improves nonalcoholic fatty liver disease in mice fed a high-fat and high-cholesterol diet. Nutr Res. 2019;64:64-71.  https://doi.org/10.1016/j.nutres.2019.01.001
  36. Yan T, Liu B, Li F, Wu B, Xiao F, He B, et al. Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation. Immunopharmacol Immunotoxicol. 2021;43(2):212-22.  https://doi.org/10.1080/08923973.2021.1879847
  37. Yan LS, Zhang SF, Luo G, Cheng BC, Zhang C, Wang YW, et al. Schisandrin B mitigates hepatic steatosis and promotes fatty acid oxidation by inducing autophagy through AMPK/mTOR signaling pathway. Metabolism. 2022;131:155200. 
  38. Wang HQ, Wan Z, Zhang Q, Su T, Yu D, Wang F, et al. Schisandrin B targets cannabinoid 2 receptor in Kupffer cell to ameliorate CCl4-induced liver fibrosis by suppressing NF-κB and p38 MAPK pathway. Phytomedicine. 2022;98:153960.  https://doi.org/10.1016/j.phymed.2022.153960
  39. Li Z, Zhao L, Xia Y, Chen J, Hua M, Sun Y. Schisandrin B Attenuates Hepatic Stellate Cell Activation and Promotes Apoptosis to Protect against Liver Fibrosis. Molecules. 2021;26(22):6882. 
  40. Yoshikawa M, Murakami T, Ueda T, Yoshizumi S, Ninomiya K, Murakami N, et al. Bioactive constituents of Chinese natural medicines. III. Absolute stereostructures of new dihydroflavonols, hovenitins I, II, and III, isolated from hoveniae semen seu fructus, the seed and fruit of Hovenia dulcis THUNB. (Rhamnaceae): inhibitory effect on alcohol-induced muscular relaxation and hepatoprotective activity. Yakugaku Zasshi. 1997;117(2):108-18. https://doi.org/10.1248/yakushi1947.117.2_108