小柴胡湯이 thioacetamide로 유발된 간섬유증 동물 모델에 미치는 영향
Effect of Sosiho-tang on a Thioacetamide-induced Liver Fibrosis Mouse Model
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms. Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting. Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen Ⅰ. Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.
Abstract
Objectives: The aim of the current study was to investigate the effect of Sosiho-tang on thioacetamide (TAA)-induced liver fibrosis in mice and to elucidate its underlying mechanisms. Methods: The mice were divided into 4 groups: Normal mice (Normal), TAA-induced control mice (Control), TAA-induced and silymarin-treated (50 mg/kg) mice (Silymarin), and TAA-induced and Sosiho-tang treated (200 mg/kg) mice (SSHT). Liver fibrosis was induced via intraperitoneal injection of TAA three times a week for 8 weeks. Silymarin and Sosiho-tang were concomitantly administered for 8 weeks. Serum and liver tissues were then collected and the anti-oxidant and inflammatory protein levels in the liver tissues were evaluated using western blotting. Results: SSHT administration significantly reduced the levels of AST, ALT, ammonia, and MPO in the serum. SSHT also significantly down-regulated liver NADPH oxidase and regulated the Nrf2/Keap1 signaling pathway. SSHT treatment downregulated the liver NF-κB levels and suppressed inflammatory cytokines. SSHT treatment also decreased bile acid-related factors, such as CYP7A1 and NTCP, and fibrosis-related factors, such as α-SMA and Collagen Ⅰ. Conclusions: Taken together, these data suggest that SSHT administration suppressed the progression of liver fibrosis by activating the Nrf2/Keap1 pathway and inhibiting NF-κB.
참고문헌 (28)
- Feng J, "Salidroside ameliorates autophagy and activation of hepatic stellate cells in mice via NF-kappaB and TGF-beta1", Smad3 pathways, 2018, pp.12, 1837~1853
- Tu T, "Hepatocytes in liver injury:Victim, bystander, or accomplice in progressive fibrosis?", J Gastroenterol Hepatol, 30(12), pp.1696~1704 (2015)
- Nieto N, "Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P4502E1-derived reactive oxygen species", Hepatology, 35(1), pp.62~73 (2002)
- Sánchez-Valle V, "Role of oxidative stress and molecular changes in liver fibrosis: a review", Curr Med Chem, 19(28), pp.4850~4860 (2012)
- 大韓藥師會, "韓藥調劑指針解說" (1995), 여강출판사
- Li J, "Xiaochaihutang attenuates liver fibrosis by activation of Nrf2 pathway in rats", Biomedicine & Pharmacotherapy, 96, pp.847~853 (2017)
- Shao S, "Xiao-Chai-Hu-Tang ameliorates tumor growth in cancer comorbid depressive symptoms via modulating gut microbiota-mediated TLR4", MyD88, Phytomedicine, pp.2021, 88[DOI]
- Chang JS, "Sho-saiko-to (Xiao-Chai-Hu-Tang)and crude saikosaponins inhibit hepatitis B virus in a stable HBV-producing cell line", Am J Chin Med, 35(2), pp.341~351 (2007)
- Jin J, "Network pharmacology and molecular docking study on the mechanism of colorectal cancer treatment using Xiao-Chai-Hu-Tang", PLoS One, 16(6), pp.e0252508~ (2021)
- 서상희, "과산화수소로 유도된 산화성 간세포 손상에 대한 소시호탕(小柴胡湯)의 효과", 대한한방내과학회지, 32(4), pp.487~496 (2011), 대한한방내과학회
- Kim DH, "Hepatoprotective Effects of Sosihotang on CCl4 induced Liver Injury in Rats", J Korean Soc Hygienic Sciences, 4(2), pp.1~6 (1998)
- Lin CC, "Renal Protective Effect of Xiao-Chai -Hu-Tang on Diabetic Nephropathy of Type 1-Diabetic Mice", Evidence Based Complement Alternative Med, 2012, pp.984024~ (2012)
- Hernandez-Gea V, "Pathogenesis of liver fibrosis", Annu Rev Pathol, 6, pp.425~456 (2011)
- Fitzhugh OG, "Liver tumors in rats fed thiourea or thioacetamide", Sci, 108(2814), pp.626~628 (1948)
- Hunter AL, "Thioacetamide -induced hepatic necrosis. Involvement of the mixed-function oxidase enzyme system", J Pharmacol Exp Ther, 200(2), pp.439~448 (1977)
- Satyabhama S, "Effects of thioacetamide on cytochrome P450 synthesis in rat liver", Biochem J, 218(2), pp.371~377 (1984)
- Kong DZ, "Xiao Chai Hu Tang, a herbal medicine, for chronic hepatitis B", Cochrane Database Syst Rev, 2019(11), pp.CD13090~ (2019)
- Hsu LM, "Acute Hepatitis Induced by Chinese Hepatoprotective Herb, Xiao-Chai-Hu-Tang", J Chin Med Assoc, 69(2), pp.86~88 (2006)
- Liang S, "The Role of NADPH Oxidases (NOXs) in Liver Fibrosis and the Activation of Myofibroblasts", Front Physiol, 7, pp.17~ (2016)
- Xu W, "The Nrf2 transcription factor protects from toxin-induced liver injury and fibrosis", Lab Invest, 88(10), pp.1068~1078 (2008)
- Schreck R, "Nuclear factor kappa B: an oxidative stress-responsive transcription factor of eukaryotic cells (a review)", Free Radic Res Commun, 17(4), pp.221~237 (1992)
- Yu Q, "PPARγββ", NF-κB and TGF-β1, J Cell Mol Med, pp.2021, 25(3)[DOI]
- Fathy M, "Modulation of inducible nitric oxide synthase pathway by eugenol and telmisartan in carbon tetrachloride -induced liver injury in rats", Life Sciences, 216, pp.207~214 (2019)
- Britton RS, "Role of free radicals in liver diseases and hepatic fibrosis", Hepatogastroenterology, 41(4), pp.343~348 (1994)
- Wang M, "Network pharmacology-based mechanism prediction and pharmacological validation of Xiaoyan Lidan formula on attenuating alphanaphthylisothiocyanate induced cholestatic hepatic injury in rats", J Ethnopharmacol, 270, pp.113816~ (2021)
- Li N, "Modification effects of SanWei GanJiang Powder on liver and intestinal damage through reversing bile acid homeostasis", Biomed Pharmacother, 116, pp.109044~ (2019)
- Zhang Y, "Chemical profile of Swertia mussotii Franch and its potential targets against liver fibrosis revealed by cross-platform metabolomics", J Ethnopharmacol, 274, pp.114051~ (2021)
- Wu JZ, "Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy", Chin J Nat Med, 19(4), pp.241~254 (2021)