|
|
|
题名
|
作者
|
年代
|
出处
|
被引量
|
| 1 | Betulinic acid hydroxamate prevents colonic inflammation and fibrosis in murine models of inflammatory bowel disease显示文摘Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) and is defined as an excessive accumulation of scar tissue in the intestinal wall. Intestinal fibrosis occurs in both forms of IBD: ulcerative colitis and Crohn’s disease. Small-molecule inhibitors targeting hypoxia-inducing factor (HIF) prolyl-hydroxylases are promising for the development of novel antifibrotic therapies in IBD. Herein, we evaluated the therapeutic efficacy of hydroxamate of betulinic acid (BHA), a hypoxia mimetic derivative of betulinic acid, against IBD in vitro and in vivo. We showed that BAH (5–20 μM) dose-dependently enhanced collagen gel contraction and activated the HIF pathway in NIH-3T3 fibroblasts;BAH treatment also prevented the loss of trans-epithelial electrical resistance induced by proinflammatory cytokines in Caco-2 cells. In two different murine models (TNBS- and DSS-induced IBD) that cause colon fibrosis, oral administration of BAH (20, 50 mg/kg·d, for 17 days) prevented colon inflammation and fibrosis, as detected using immunohistochemistry and qPCR assays. BAH-treated animals showed a significant reduction of fibrotic markers (Tnc, Col1a2, Col3a1, Timp-1, α-SMA) and inflammatory markers (F4/80+, CD3+, Il-1β, Ccl3) in colon tissue, as well as an improvement in epithelial barrier integrity and wound healing. BHA displayed promising oral bioavailability, no significant activity against a panel of 68 potential pharmacological targets and was devoid of genotoxicity and cardiotoxicity. Taken together, our results provide evidence that oral administration of BAH can alleviate colon inflammation and colitis-associated fibrosis, identifying the enhancement of colon barrier integrity as a possible mechanism of action, and providing a solid rationale for additional clinical studies. | María EPrados Adela García-Martín Juan DUnciti-Broceta Belén Palomares Juan ACollado Alberto Minassi Marco ACalzado Giovanni Appendino Eduardo Muñoz | 2021 | Acta Pharmacologica Sinica2021，42，7： | 3 |
| 2 | A new P-glycoproteininhibitor from the caper spurge(Euphorbia lathyris)显示文摘 | G Appendino A D Pictor G Conseil | 2003 | J NatProd2003，66，1： | 1 |
| 3 | Sesquiterpenoids from Pallenis spinosa显示文摘 | Appendino G Jakupovic J Jakupovic S | 1997 | Phytochemistry1997，46，6： | 1 |
| 4 | Prenylalted Coumarins and Sesquiterpenoids from Ferula Communis 显示文摘 | Valle MG Appendino G Nano GM | 1987 | Phytochem1987，26，1： | 1 |
| 5 | A new P-glycoprotein inhibitor from the caper spurge(Euphorbia lathyris)显示文摘 | Appendino G Porta C D Conseil G | 2003 | J Nat Prod2003，，： | 1 |
| 6 | Oxygenated Sesquiterpenoids from a Nonpoisonous Sardinian Chemotype of Giant fennel (ferula communis) 显示文摘 | Appendino G Cravotto F Sterner O | 2001 | J Nat Prod2001，64，： | 1 |
| 7 | Daucne Esters from Ferula Arrigonii 显示文摘 | Appendino G Jakupovi J Alloatti S | 1997 | Phytochem1997，45，4： | 1 |
| 8 | Joining of C/C composites to copper显示文摘 | Appendino P Casalegno V Ferraris M | 2003 | Fusion engineering and design2003，6668，2003： | 1 |
| 9 | Acid and base catalysed rearrangement of 9,10-dioxotaxanes显示文摘 | Appendino G Jakupovic J Varese M | 1996 | Tetrahedron Lett1996，37，5： | 1 |
| 10 | Antibacterial cannabinoids from Cannabis sativa: a structure-activity study显示文摘 | Appendino G Gibbons S Giana A | 2008 | Journal Of Natural Products2008，71，8： | 1 |
| 11 | Proposal for a new technique to join C/C composites to copper 显示文摘 | Appendino P Ferraris M Casalegno V | 2006 | J Nuel Mater2006，348，： | 1 |
| 12 | Morphoagronomic and biochemical variation in an Argen-tinean landrace of wheat显示文摘 | TRANQUILLI G APPENDINO ML PF-LUGER L | 2000 | Genetic Resources and Crop Evolution2000，47，： | 1 |
| 13 | Primary bladder phaeochromocytoma diagnosed by a vet 显示文摘 | Oderda M Michelon F Appendino M | 2010 | Scand J Urol Neph- rol2010，44，： | 1 |
| 14 | A new p-cglycoprotein inhibitor from the caper spurge (Euphorbia lathyris) 显示文摘 | Appendino G Conseil G Pietro A D etal | 2003 | J Nat Prod2003，66，： | 1 |
| 15 | Protective glass coating for carbon-carbon composites显示文摘 | Isola C Appendino P Bosco F | 1998 | Carbon1998，36，78： | 1 |
| 16 | The stereochemistry of ar- glabin, a cytotoxic guaianolide from Artemisia myriantha 显示文摘 | Appendino G Gariboldi P Menichini F | 1991 | Fitote- rapia1991，62，： | 1 |
| 17 | A new P-glycoprotein inhibitor from the caper spurge(Euphorbia lathyris)显示文摘 | Appendino G Porta C D Conseil G | 2003 | J Nat Prod2003，，： | 1 |
| 18 | Halogenation of a capsaicin analogue leads to novel vanilloid TRPV1 receptor antagonists显示文摘 | Appendino G Harrison S De Petrocellis L | 2003 | Br J Pharmacol2003，139，8： | 1 |
| 19 | Polycyclic diterpenoidsfrom Euphorbia charac-ias显示文摘 | APPENDINO G BELLORO E BALLERO M | 2000 | Fitoterapia2000，71，： | 1 |
| 20 | Direct joining of CFC to copper显示文摘 | P APPENDINO | 2004 | Journal of Nuclear Materials2004，，329： | 1 |
您所在的机构暂未开通此部分的功能，请联系管理员