Abstract：
:The therapeutic efficacy of immunosuppressive agents has been intensively studied for colitis management. We synthesized a series of andrographolide derivatives and reported their structure-activity-relationship and anti-inflammatory activity in our previous studies. Among these derivatives, compound 3b exhibited the most potent immunosuppressive activity. In the present study, we assessed the efficacy of 3b in dextran sulfate sodium (DSS)-induced model of acute colitis. Compound 3b was administered intragastrically. The therapeutic effect of 3b was evaluated using disease score and immune cell infiltration. The effect of 3b on Toll-like receptor 4/NF-κB and β-catenin signaling was primarily determined by using immunohistochemistry staining and quantitative real-time PCR. The crosstalk between NF-κB and β-catenin signaling was then assessed in HCT-116 cells. Treatment with 3b significantly downregulated the disease activity index and suppressed the histologic evidence of inflammation in DSS-induced model of acute colitis. Compound 3b inhibited proinflammatory cytokine expression at both the serum and transcription levels. Treatment with 3b also upregulated the number of PCNA-positive and goblet cells in the intestinal crypt and the intestinal expression of mRNA levels of β-catenin target genes. β-Catenin level regulation affected the antiinflammation and anti-apoptotic activities of 3b. This study demonstrated that 3b, a novel andrographolide derivative, suppressed inflammation and significantly reversed colitis pathology. The outcome of colitis treatment with an immunosuppressive agent depends upon the intestinal expression and mutation status of β-catenin.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Guo BJ,Liu Z,Ding MY,Li F,Jing M,Xu LP,Wang YQ,Zhang ZJ,Wang Y,Wang D,Zhou GC,Wang Ydoi
10.1016/j.bcp.2019.03.019subject
Has Abstractpub_date
2019-05-01 00:00:00pages
416-424eissn
0006-2952issn
1873-2968pii
S0006-2952(19)30105-4journal_volume
163pub_type
杂志文章abstract：:In this study we compared two methods, electron spin resonance (ESR) spectroscopy and high performance liquid chromatography (HPLC), which are currently used to detect directly hydroxyl radical (OH.) formation in the ischemic and reperfused heart. Isolated buffer-perfused rat hearts were subjected to 30 min of normoth...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
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doi：10.1016/0006-2952(87)90189-4
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90553-u
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pub_type： 杂志文章,评审
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journal_title：Biochemical pharmacology
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pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90184-k
更新日期：1992-05-28 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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更新日期：1989-01-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90592-7
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pub_type： 杂志文章
doi：10.1016/j.bcp.2011.01.015
更新日期：2011-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2003.08.007
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journal_title：Biochemical pharmacology
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journal_title：Biochemical pharmacology
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更新日期：2014-04-15 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.013
更新日期：2010-12-01 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.08.013
更新日期：2005-11-25 00:00:00
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
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journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90728-8
更新日期：1986-06-15 00:00:00
abstract：:The genetically controlled polymorphic oxidation of debrisoquine and sparteine is caused by the absence or functional deficiency of a cytochrome P-450 isozyme. In order to elucidate the mechanisms underlying the differences in cytochrome P-450 function we have studied the 1'-hydroxylation of the prototype drug bufural...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90573-9
更新日期：1987-12-01 00:00:00
abstract：:gamma-Carbolines are tricyclic aromatic compounds which intercalate into DNA base pairs and exhibit significant cytotoxic and antitumor activities. These compounds which are structurally related to ellipticine by deletion of an aromatic ring, induce DNA breaks in cultured L1210 cells. Since the mechanism of cytotoxic ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90144-a
更新日期：1990-02-15 00:00:00
