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| 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 structure-activity relationship study on N-arachidonoyl-amino acids as possible endog- enous inhibitors of fatty acid amide hydrolase 显示文摘 | Grazia CM Minassi A Ligresti A | 2004 | Biochem Biophys Res Commun2004，314，1： | 1 |
| 3 | Protective effect and relation structure-activity of nonivamide and iododerivatives in several models of lipid oxidation显示文摘 | Antonella Rosa Giovanni Appendino M. Paola Melis Monica Deiana Angela Atzeri Incani Alessandra Alberto Minassi M. Assunta Dessì | 2009 | Chemico-Biological Interactions2009，，2： | 1 |
| 4 | In vivo estrogenic comparisons of Trifolium pratense (red clover) Humulus lupulus (hops), and the pure compounds isoxanthohumol and 8-prenylnaringenin显示文摘 | Cassia R. Overk Jian Guo Lucas R. Chadwick Daniel D. Lantvit Alberto Minassi Giovanni Appendino Shao-Nong Chen David C. Lankin Norman R. Farnsworth Guido F. Pauli Richard B. van Breemen Judy L. Bolton | 2008 | Chemico-Biological Interactions2008，，1： | 1 |
| 5 | The reaction of cinnamaldehyde and cinnam(o)yl derivatives with thiols显示文摘Spurred by the alleged relevance of the thia-Michael reaction in the bioactivity of various classes of cinnam(o)yl natural products and by the development of a quick NMR assay to study this reaction, we have carried out a systematic study of the 'native' reactivity of these compounds with dodecanethiol and cysteamine as models, respectively, of simple thiols and reactive protein thiols that can benefit from iminium ion catalysis in Michael reactions. Cinnamoyl esters and amides, as well as cinnamyl ketones and oximes, did not show any reactivity with the two probe thiols, while cinnamaldehyde(1a) reacted with cysteamine to afford a mixture of a thiazoline derivative and compounds of multiple addition, and with aliphatic thiols to give a single bis-dithioacetal(6). Chalchones and their vinylogous C5-curcuminoid derivatives were the only cinnamoyl derivatives that gave a thiaMichael reaction. From a mechanistic standpoint, loss of conjugation in the adduct might underlie the lack of a native Michael reactivity. This property is restored by the presence of another conjugating group on the carbonyl, as in chalcones and C5-curcuminoids. A critical mechanistic revision of the chemical and biomedical literature on cinnamaldehyde and related compounds seems therefore required. | Alessandro Autelitano Alberto Minassi Alberto Pagani Orazio Taglialatela-Scafati Giovanni Appendino | 2017 | Acta Pharmaceutica Sinica B2017，7，4： | 0 |
| 6 | The dimerization of ⊿~9-tetrahydrocannabinolic acid A(THCA-A)显示文摘The renewed interest in dimeric salicylates as broad-spectrum anti-inflammatory and antidiabetic agents provided a rationale to investigate the dimerization of the substituted salicylate D9-tetrahydrocannabinolic acid(THCA-A, 3 a) as a strategy to solve its instability to decarboxylation and to generate analogues and/or pro-drugs of this native pre-cannabinoid. Activation of the carboxylic group with the DCC-HOBt-DMAP protocol afforded a high yield of the OBt ester 4, that was next converted into the highly crystalline di-depsidic dimer 5 upon treatment with DMAP. The mono-depsidic dimer 6 was also formed when the reaction was carried out with partially decarboxylated THCA-A samples. The structure of the depsidic dimers was established by spectroscopic methods and by aminolysis of 5 into the pre-cannabinoid amide 7. Both dimers showed excellent shelf stability and did not generate significant amounts of D9-THC upon heating. However, only the didepsidic dimer 5 activated PPAR-g, the major target of pre-cannabinoids, but strong binding to serum proteins abolished this activity, also shielding it from the action of esterases. | Arben Cuadari Federica Pollastro Juan D.Unciti-Broceta Diego Caprioglio Alberto Minassi Annalisa Lopatriello Eduardo Munoz Orazio Taglialatela-Scafati Giovanni Appendino | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 0 |
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