Isosecotanapartholide

Effect of isosecotanapartholide isolated from Artemisia princeps Pampanini on IL33 production and STAT1 activation in HaCaT keratinocytes.[Pubmed:28447741]

Mol Med Rep. 2017 May;15(5):2681-2688.

The present study aimed to investigate the antiinflammatory effect and mechanism of action of Isosecotanapartholide (ISTP), isolated from Artemisia princeps Pampanini extract (APE). The effects of ISTP and APE on the proliferation of human keratinocytes following stimulation by tumor necrosis factoralpha/interferongamma were assessed. ISTP and APE downregulated the expression levels of signal transducer and activator of transcription1 (STAT1), and reduced interleukin33 (IL33) production. ISTP and APE inhibited the mRNA expression levels of thymus and activationregulated chemokine (TARC/CCL17) in a dosedependent manner. Western blot analysis demonstrated that ISTP and APE dosedependently inhibited protein expression levels of intercellular adhesion molecule1 and phosphorylation of STAT1. The results of the present study indicate that ISTP may inhibit TARC/CCL17 production in human epidermal keratinocytes via the STAT1 signaling pathway and may be associated with the inhibition of IL33 production. The current study indicated that ISTP is an active component in APE and may be a potential therapeutic agent for the treatment of inflammatory skin disorders.

Differential growth inhibitory effects of highly oxygenated guaianolides isolated from the Middle Eastern indigenous plant Achillea falcata in HCT-116 colorectal cancer cells.[Pubmed:23860275]

Molecules. 2013 Jul 15;18(7):8275-88.

Medicinal plants play a crucial role in traditional medicine and in the maintenance of human health worldwide. Sesquiterpene lactones represent an interesting group of plant-derived compounds that are currently being tested as lead drugs in cancer clinical trials. Achillea falcata is a medicinal plant indigenous to the Middle Eastern region and belongs to the Asteraceae family, which is known to be rich in sesquiterpene lactones. We subjected Achillea falcata extracts to bioassay-guided fractionation against the growth of HCT-116 colorectal cancer cells and identified four secotanapartholides, namely 3-beta-methoxy-Isosecotanapartholide (1), Isosecotanapartholide (2), tanaphallin (3), and 8-hydroxy-3-methoxyIsosecotanapartholide (4). Three highly oxygenated guaianolides were isolated for the first time from Achillea falcata, namely rupin A (5), chrysartemin B (6), and 1beta, 2beta-epoxy-3beta,4alpha,10alpha-trihydroxyguaian-6alpha,12-olide (7). These sesquiterpene lactones showed no or minor cytotoxicity while exhibiting promising anticancer effects against HCT-116 cells. Further structure-activity relationship studies related the bioactivity of the tested compounds to their skeleton, their lipophilicity, and to the type of functional groups neighboring the main alkylating center of the molecule.

Inhibitors of inducible nitric oxide synthase expression from Artemisia iwayomogi.[Pubmed:12735688]

Arch Pharm Res. 2003 Apr;26(4):301-5.

Nitric oxide (NO) is an important bioactive agent that mediates a wide variety of physiological and pathophysiological events. NO overproduction by inducible nitric oxide synthase (iNOS) results in severe hypotension and inflammation. This investigation is part of a study to discover new iNOS inhibitors from medicinal plants using a macrophage cell culture system. Two sesquiterpenes (1 and 2) were isolated from Artemisia iwayomogi (Compositae) and were found to inhibit NO synthesis (IC50 3.64 microg/mL and 2.81 microg/mL, respectively) in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Their structures were identified as 3-O-methyl-Isosecotanapartholide (1) and iso-secotanapartholide (2). Compounds 1 and 2 inhibited the LPS-induced expression of the iNOS enzyme in the RAW 264.7 cells. The inhibition of NO production via the down regulation of iNOS expression may substantially modulate the inflammatory responses.