Shen Y, Luo Q, Xu H et al.Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis. Biochem Pharmacol 82:260-268

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Biochemical pharmacology (Impact Factor: 5.01). 05/2011; 82(3):260-8. DOI: 10.1016/j.bcp.2011.04.013
Source: PubMed


Facilitating T-cell apoptosis is implicated as an effective therapeutic strategy for treatment of T cell-mediated disease, including inflammatory bowel disease. Here, we report that astin C, a plant cyclopeptide isolated from the roots of Aster tataricus (Compositae), induced apoptosis of activated T cells in a mitochondria-dependent but Fas-independent manner in that such activity was still observed in T cells from Fas-mutated MRLlpr/lpr mice. Although caspase 8 was not activated, astin C treatment led to the cleavage of caspase 9 and caspase 3, the upregulation of Bad protein expression as well as release of cytochrome c in activated T cells. Astin C did not induce the expression of GRP78 and GADD153, excluding involvement of endoplasmic reticulum stress-mediated pathway. Moreover, oral administration of astin C protected mice against TNBS-induced colonic inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Administering astin C significantly decreased serum levels of TNF-α, IL-4 and IL-17, accompanied with the induction of apoptosis in activated T cells in vivo. The results demonstrate, for the first time, the ability of astin C to induce apoptosis in activated T cells and its potential use in the treatment of colonic inflammation.

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Available from: Qiong Luo, Jul 01, 2014
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    • "There are three different death signaling pathways leading to apoptosis: the extrinsic death receptor-dependent pathway, the intrinsic mitochondria-dependent pathway and the intrinsic ER stress-mediated pathway 46. For the intrinsic mitochondria-dependent pathway, the release of cytochrome c from mitochondria into the cytosol is fundamental to apoptosome formation and downstream caspase-3 activation 47. "
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    • "It has been reported that the main components of this plant are terpenoids, sterols, flavonoids, and cyclopeptides [2] [3]. Among them cyclopeptides and triterpenoids are the main metabolites with antitussive, expectorant and immunosuppressive activities [4] [5] [6] [7] [8]. Shionanetype triterpenoids with a unique all six-membered tetracyclic skeleton and 3-oxo-4-monomethyl group are one of the main triterpenoid components of A. tataricus [9] [10], but only 9 ones were reported from natural resources (i. "
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    ABSTRACT: Six new shionane-type triterpenes, astershionones A-F (1-6), were obtained from the roots and rhizomes of Aster tataricus. Their structures were elucidated on the basis of spectroscopic data, mainly NMR and MS data. The absolute configuration of 1 was determined by single crystal X-ray diffraction analysis and CD analysis. 3 showed inhibitory activity against HBsAg and HBeAg secretion with IC50 values of 23.0 and 23.1μM, and cytotoxicity against HepG 2.2.15 cells with CC50 value of 170.5μM. 3 also exhibited inhibitory activity against HBV DNA replication with IC50 value of 22.4μM.
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