Antiproliferative triterpenes from the leaves and twigs of Juglans sinensis on HSC-T6 cells.

Bioassay-guided fractionation of an 80% MeOH extract of leaves and twigs of Juglan sinensis has resulted in the isolation of four new triterpenes (1-4) and 17 known triterpenes (5-21). The new compounds were determined to be 1-oxo-3β,23-dihydroxyolean-12-en-28-oic acid 28-O-β-D-glucopyranoside (1), 1-oxo-3β-hydroxyolean-18-ene (2), 3β,23-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (3), and 3β,22α-dihydroxyurs-12-en-28-oic acid 28-O-β-D-glucopyranoside (4) by spectroscopic analysis. Compounds 2, 13, 15, and 21 showed antiproliferative activities (14.2, 14.8, 15.6, and 11.0% at 100 μM, respectively) in HSC-T6 cells. Flow cytometry assays revealed that these compounds inhibited HSC-T6 proliferation by inducing apoptosis.

[1]  P. Agrawal,et al.  NMR spectroscopy in the structural elucidation of oligosaccharides and glycosides. , 1992, Phytochemistry.

[2]  S. Zographos,et al.  Naturally occurring pentacyclic triterpenes as inhibitors of glycogen phosphorylase: synthesis, structure-activity relationships, and X-ray crystallographic studies. , 2008, Journal of medicinal chemistry.

[3]  M. Zern,et al.  Hepatic stellate cells: a target for the treatment of liver fibrosis , 2000, Journal of Gastroenterology.

[4]  G. Cordell,et al.  Constituents of the leaves and twigs of Calyptranthes pallens collected from an experimental plot in Southern Florida. , 2005, Journal of natural products.

[5]  Seung-Hyung Kim,et al.  Immunomodulatory effect of Juglans sinensis, Psoralea corylifolia, Cheong-a-hwan extract and cyclosporine A on Th1(IFN-γ)/Th2(IL-4) cytokine balance, eosinophil accumulation in a murine model of asthma , 2008 .

[6]  M. Domenico,et al.  New therapeutic approaches to liver fibrosis: a practicable route? , 2008 .

[7]  Yin Han,et al.  Cytotoxic diarylheptanoids from the pericarps of walnuts (Juglans regia). , 2008, Planta medica.

[8]  Eun-Young Kim,et al.  Protective Effects of Cinnamomum cassia Blume in the Fibrogenesis of Activated HSC-T6 Cells and Dimethylnitrosamine-Induced Acute Liver Injury in SD Rats , 2010, Bioscience, biotechnology, and biochemistry.

[9]  H. Ji,et al.  Antifibrotic effects of ZK14, a novel nitric oxide-donating biphenyldicarboxylate derivative, on rat HSC-T6 cells and CCl4-induced hepatic fibrosis , 2010, Acta Pharmacologica Sinica.

[10]  A. Shashkov,et al.  Triterpene glycosides from Kalopanax septemlobum. VII. Minor glycosides from stems of Kalopanax septemlobum var. maximowiczii and Kalopanax septemlobum var. typicum , 2006, Chemistry of Natural Compounds.

[11]  Jun Yu,et al.  Stephania tetrandra prevents and regresses liver fibrosis induced by carbon tetrachloride in rats , 2009, Journal of gastroenterology and hepatology.

[12]  Á. Ravelo,et al.  13C NMR spectra of olean-18-ene derivatives , 1981 .

[13]  V. Křen,et al.  Biocatalyzed Generation of Molecular Diversity: Selective Modification of the Saponin Asiaticoside , 2005 .

[14]  Christopher J. Parsons,et al.  Mechanisms of liver fibrosis. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[15]  T. G. Fourie,et al.  A pentacyclic triterpene acid, with anti-ulcer properties, from Cussonia natalensis☆ , 1989 .

[16]  M. A. Khuroo,et al.  Lupene derivatives from Skimmia laureola , 1988 .

[17]  Toshiyuki Fukuda,et al.  Antioxidative polyphenols from walnuts (Juglans regia L.). , 2003, Phytochemistry.

[18]  Ren-bo An,et al.  Free Radical Scavenging and Hepatoprotective Constituents from the Leaves of Juglans sinensis , 2005, Archives of pharmacal research.

[19]  S. Mahato,et al.  Triterpenoids and their glycosides from Terminalia chebula. , 1993 .

[20]  Kyung-Tae Lee,et al.  Saponins from Cussonia bancoensis and their inhibitory effects on nitric oxide production. , 2003, Journal of natural products.

[21]  H. Kasper,et al.  Morphologische Veränderungen der medikamenteninduzierten Leberschädigung , 2006, Der Pathologe.

[22]  H. Sakagami,et al.  Production of bioactive triterpenes by Eriobotrya japonica calli. , 2002, Phytochemistry.

[23]  R. Weis,et al.  Complete assignments of 1H and 13C NMR resonances of oleanolic acid, 18α‐oleanolic acid, ursolic acid and their 11‐oxo derivatives , 2003 .

[24]  D. Schuppan,et al.  Hepatitis C and liver fibrosis , 2003, Cell Death and Differentiation.

[25]  Anping Chen,et al.  The Antioxidant (–)-Epigallocatechin-3-gallate Inhibits Rat Hepatic Stellate Cell Proliferation in Vitro by Blocking the Tyrosine Phosphorylation and Reducing the Gene Expression of Platelet-derived Growth Factor-β Receptor* , 2003, Journal of Biological Chemistry.

[26]  R. Urtasun,et al.  Alcohol and liver fibrosis. , 2009, Seminars in liver disease.

[27]  Y. Okada,et al.  A new triterpenoid isolated from Lagerstronemia speciosa (L.) Pers. , 2003, Chemical & pharmaceutical bulletin.

[28]  Y. Fukuyama,et al.  Oleanane-type triterpenes from Viburnum awabuki , 1998 .

[29]  T. Mosmann.  Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[30]  R. Tan,et al.  Anti-proliferative and pro-apoptotic effects of tectorigenin on hepatic stellate cells. , 2010, World journal of gastroenterology.

[31]  S. Friedman,et al.  Liver fibrogenesis and the role of hepatic stellate cells: New insights and prospects for therapy , 1999, Journal of gastroenterology and hepatology.

[32]  Young Hyun Park,et al.  Triterpenoic acids of Prunella vulgaris var. lilacina and their cytotoxic activities In Vitro , 2008, Archives of pharmacal research.

[33]  S. Friedman,et al.  Mechanisms of hepatic fibrogenesis. , 2008, Gastroenterology.