Cirsilineol

Biochem Pharmacol. 2010 Jan 15;79(2):229-38.

Novel immunomodulatory properties of cirsilineol through selective inhibition of IFN-gamma signaling in a murine model of inflammatory bowel disease.[Pubmed: 19698701]

Regulation of signal transducer and activator of transcription (STAT) 1 signaling is being explored as a new approach to the treatment of inflammatory bowel diseases. However, few chemicals have been reported to inhibit IFN-gamma/STAT1 signaling for Crohn's disease therapy.
METHODS AND RESULTS:
In the present study, we found that Cirsilineol, a small natural compound isolated from Artemisia vestita, significantly ameliorated trinitro-benzene sulfonic acid (TNBS)-induced T-cell-mediated experimental colitis in mice, which was closely associated with reduced autoreactive T-cell proliferation and activation. Moreover, the regulatory action of pro-inflammatory and anti-inflammatory cytokine by Cirsilineol treatment was found to decrease the activity of effector Th1 cells but increase the activity of regulatory T cells as characterized by down-regulation of IFN-gamma and corresponding up-regulation of IL-10 and TGF-beta. The therapeutic effect of Cirsilineol was attributable to a novel regulatory mechanism with selective inhibiting IFN-gamma signaling in colonic lamina propria CD4(+) T cells, which was mediated through down-regulating STAT1 activation and T-bet expression. Furthermore, Cirsilineol was found to down-regulate the activation of JAK2, a critical kinase for IFN-gamma/STAT1 signaling, and abrogate the expression of T-bet, resulting in markedly decreased proliferation and activation of T cells in vitro. Importantly, the inhibition of IFN-gamma/STAT1 signaling by Cirsilineol was reversible in the presence of high level of IFN-gamma.
CONCLUSIONS:
These results strongly suggest that Cirsilineol might be potentially useful for treating T-cell-mediated human inflammatory bowel diseases.

J Pharm Pharmacol. 2008 Nov;60(11):1523-9.

Cirsilineol inhibits proliferation of cancer cells by inducing apoptosis via mitochondrial pathway.[Pubmed: 18957174]

Cirsilineol (4',5-dihydroxy-3',6,7-trimethoxyflavone) is a compound isolated from the herb of Artemisia vestita Wall (Compositae).
METHODS AND RESULTS:
In this study, we aimed at examining the anti-proliferative activity of Cirsilineol against multiple types of cancer cells and the underlying mechanisms. Cirsilineol significantly inhibited proliferation of Caov-3, Skov-3, PC3 and Hela cells in a concentration-dependent manner. The compound also dose-dependently induced apoptosis in Caov-3 cells, as determined by annexin V/propidium iodide staining. Besides, Cirsilineol induced a remarkable change in mitochondrial membrane potential and caused release of cytochrome c to cytosol. Furthermore, the compound caused a marked activation of capase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP).
CONCLUSIONS:
These results suggested that the induction of apoptosis via the mitochondrial pathway was involved in the anti-proliferative activity of Cirsilineol against cancer cells.