Anti-fibrotic effects of Orostachys japonicus A. Berger (Crassulaceae) on hepatic stellate cells and thioacetamide-induced fibrosis in rats
0
조회
0
다운로드
5
인용
0
참고문헌
키워드
초록
BACKGROUND/OBJECTIVE: Orostachys japonicus A. Berger (Crassulaceae) has been used in traditional herbal medicines in Korea and other Asian countries to treat various diseases, including liver disorders. In the present study, the anti-fibrotic effects of O. japonicus extract (OJE) in cellular and experimental hepatofibrotic rat models were investigated. MATERIALS/METHODS: An in vitro hepatic stellate cells (HSCs) system was used to estimate cell viability, cell cycle and apoptosis by MTT assay, flow cytometry, and Annexin V-FITC/PI staining techniques, respectively. In addition, thioacetamide (TAA)-induced liver fibrosis was established in Sprague Dawley rats. Briefly, animals were divided into five groups (n = 8): Control, TAA, OJE 10 (TAA with OJE 10 mg/kg), OJE 100 (TAA with OJE 100 mg/kg) and silymarin (TAA with Silymarin 50 mg/kg). Fibrosis was induced by treatment with TAA (200 mg/kg, i.p.) twice per week for 13 weeks, while OJE and silymarin were administered orally two times per week from week 7 to 13. The fibrotic related gene expression serum biomarkers glutathione and hydroxyproline were estimated by RT-PCR and spectrophotometry, respectively, using commercial kits. RESULTS: OJE (0.5 and 0.1 mg/ mL) and silymarin (0.05 mg/mL) treatment significantly (P < 0.01 and P < 0.001) induced apoptosis (16.95% and 27.48% for OJE and 25.87% for silymarin, respectively) in HSC-T6 cells when compared with the control group (9.09%). Further, rat primary HSCs showed changes in morphology in response to OJE 0.1 mg/mL treatment. In in vivo studies, OJE (10 and 100 mg/kg) treatment significantly ameliorated TAA-induced alterations in levels of serum biomarkers, fibrotic related gene expression, glutathione, and hydroxyproline (P < 0.05-P < 0.001) and rescued the hist
Abstract
BACKGROUND/OBJECTIVE: Orostachys japonicus A. Berger (Crassulaceae) has been used in traditional herbal medicines in Korea and other Asian countries to treat various diseases, including liver disorders. In the present study, the anti-fibrotic effects of O. japonicus extract (OJE) in cellular and experimental hepatofibrotic rat models were investigated. MATERIALS/METHODS: An in vitro hepatic stellate cells (HSCs) system was used to estimate cell viability, cell cycle and apoptosis by MTT assay, flow cytometry, and Annexin V-FITC/PI staining techniques, respectively. In addition, thioacetamide (TAA)-induced liver fibrosis was established in Sprague Dawley rats. Briefly, animals were divided into five groups (n = 8): Control, TAA, OJE 10 (TAA with OJE 10 mg/kg), OJE 100 (TAA with OJE 100 mg/kg) and silymarin (TAA with Silymarin 50 mg/kg). Fibrosis was induced by treatment with TAA (200 mg/kg, i.p.) twice per week for 13 weeks, while OJE and silymarin were administered orally two times per week from week 7 to 13. The fibrotic related gene expression serum biomarkers glutathione and hydroxyproline were estimated by RT-PCR and spectrophotometry, respectively, using commercial kits. RESULTS: OJE (0.5 and 0.1 mg/ mL) and silymarin (0.05 mg/mL) treatment significantly (P < 0.01 and P < 0.001) induced apoptosis (16.95% and 27.48% for OJE and 25.87% for silymarin, respectively) in HSC-T6 cells when compared with the control group (9.09%). Further, rat primary HSCs showed changes in morphology in response to OJE 0.1 mg/mL treatment. In in vivo studies, OJE (10 and 100 mg/kg) treatment significantly ameliorated TAA-induced alterations in levels of serum biomarkers, fibrotic related gene expression, glutathione, and hydroxyproline (P < 0.05-P < 0.001) and rescued the hist
참고문헌 (33)
- Giannandrea M, "Diverse functions of matrix metalloproteinases during fibrosis", Dis Model Mech, 7, pp.193~203 (2014)
- Popper H, "Hepatic fibrosis. Correlation of biochemical and morphologic investigations", Am J Med, 49, pp.707~721 (1970)
- Friedman SL, "Mechanisms and therapy of hepatic fibrosis: report of the AASLD Single Topic Basic Research Conference", Hepatology, 32, pp.1403~1408 (2000)
- Rudolph KL, "Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery", Science, 287, pp.1253~1258 (2000)
- Geerts A, "History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells", Semin Liver Dis, 21, pp.311~335 (2001)
- Lee JJ, "Liver fibrosis protective effect of Hovenia dulcis fruit.", Curr Top Nutraceutical Res, 12, pp.43~50 (2014)
- Friedman SL, "Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver", Physiol Rev, 88, pp.125~172 (2008)
- 이수정, "와송과 한약재 복합물의 in vitro 생리활성 평가", 한국식품영양과학회지, 41(3), pp.295~301 (2012), 한국식품영양과학회
- Kim JK, "Illustrated Natural Drugs" (1984), Namsandang Publishing Co
- 이수정, "건조 방법에 따른 와송의 항산화 효과", 한국식품영양과학회지, 37(5), pp.605~611 (2008), 한국식품영양과학회
- 윤진아, "손바닥선인장 복합물이 당뇨 쥐의 혈당 및 지질대사에 미치는 영향", 한국식품영양학회지, 22(1), pp.48~56 (2009), 한국식품영양학회
- 이수정, "Hypolipidemic and hypoglycemic effects of Orostachys japonicus A. Berger extracts in streptozotocin-induced diabetic rats", Nutrition Research and Practice, 5(4), pp.301~307 (2011), 한국영양학회
- Hendriks HF, "Perisinusoidal fat-storing cells are the main vitamin A storage sites in rat liver", Exp Cell Res, 160, pp.138~149 (1985)
- Knook DL, "Fat-storing cells of the rat liver. Their isolation and purification", Exp Cell Res, 139, pp.468~471 (1982)
- Ellman GL, "Tissue sulfhydryl groups", Arch Biochem Biophys, 82, pp.70~77 (1959)
- Takayama T, "Control of oxalate formation from L-hydroxyproline in liver mitochondria", J Am Soc Nephrol, 14, pp.939~946 (2003)
- Gressner AM, "The cell biology of liver fibrogenesis - an imbalance of proliferation, growth arrest and apoptosis of myofibroblasts", Cell Tissue Res, 292, pp.447~452 (1998)
- Friedman SL, "Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications", Nat Clin Pract Gastroenterol Hepatol, 1, pp.98~105 (2004)
- Johnston DE, "Special considerations in interpreting liver function tests", Am Fam Physician, 59, pp.2223~2230 (1999)
- McClatchey KD, "Clinical Laboratory Medicine" (2002), Lippincott Wiliams & Wilkins
- Bruck R, "Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats", J Hepatol, 40, pp.86~93 (2004)
- Krane SM, "The importance of proline residues in the structure, stability and susceptibility to proteolytic degradation of collagens", Amino Acids, 35, pp.703~710 (2008)
- Pálfi VK, "How stable is a collagen triple helix? An ab initio study on various collagen and beta-sheet forming sequences", J Comput Chem, 29, pp.1374~1386 (2008)
- Verrecchia F, "Transforming growth factor-beta and fibrosis", World J Gastroenterol, 13, pp.3056~3062 (2007)
- Liu Y, "Inhibition of PDGF, TGF-beta, and Abl signaling and reduction of liver fibrosis by the small molecule Bcr-Abl tyrosine kinase antagonist Nilotinib", J Hepatol, 55, pp.612~625 (2011)
- Jakowlew SB, "Transforming growth factor-beta (TGF-beta) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-beta", Cell Regul, 2, pp.535~548 (1991)
- Hori N, "Hemodynamic characterization in experimental liver cirrhosis induced by thioacetamide administration", Dig Dis Sci, 38, pp.2195~2202 (1993)
- Park HJ, "Flavonoids from the whole plants of Orostachys japonicus", Arch Pharm Res, 14, pp.167~171 (1991)
- Yoon Y, "Protective effects of Orostachys japonicus A. Berger (Crassulaceae) on H2O2-induced apoptosis in GT1-1 mouse hypothalamic neuronal cell line", J Ethnopharmacol, 69, pp.73~78 (2000)
- Na Young Yoon, "A Potent Anti-Complementary Acylated Sterol Glucoside from Orostachys japonicus", Archives of Pharmacal Research, 28(8), pp.892~896 (2005), 대한약학회
- Hernández-Ortega LD, "Quercetin improves hepatic fibrosis reducing hepatic stellate cells and regulating pro-fibrogenic", anti-fibrogenic molecules balance, 2012, pp.27, 1865~1872
- Zhou YP, "Preliminary exploration on anti-fibrosis effect of Kaempferol in mice with Schistosoma Japonicum infection", Eur J Inflamm, 11, pp.161~168 (2013)
- Hsieh SC, "Gallic acid selectively induces the necrosis of activated hepatic stellate cells via a calcium-dependent calpain I activation pathway", Life Sci, 102, pp.55~64 (2014)