Budlein A from Viguiera robusta

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• 作者：Roberto Nicolete ; Nilton S. Arakawa ; Cristina Rius ; Auro Nomizo ; Peter J. Jose ; Fern ; o B. Da Costa ; Marí ; a-Jesú ; s Sanz ; Lú ; cia H. Faccioli
• 关键词：Budlein A ; Viguiera robusta ; Leukocyte-endothelium ; LPS-stimulated cells ; Cytokines ; Chemokines
• 刊名：Phytomedicine
• 出版年：2009
• 出版时间：October 2009
• 年：2009
• 卷：16
• 期：10
• 页码：904-915
• 全文大小：563 K

文摘

Budlein A has been reported to exert some analgesic and anti-inflammatory properties. In this study, we have evaluated its effect on LPS-induced leukocyte recruitment in vivo and the mechanisms involved in its anti-inflammatory activity. In vivo, intravital videomicroscopy was used to determine the effects of budlein A on LPS-induced leukocyte-endothelial cell interactions in the murine cremasteric microcirculation. In vitro, the effects of budlein A on LPS-induced cytokine, chemokine and nitrites release, T-cell proliferative response as well as cell adhesion molecule expression (CAM) were evaluated. In vivo, intraperitoneal administration of budlein A (2.6 mM/kg) caused a significant reduction of LPS-induced leukocyte rolling flux, adhesion and emigration by 84, 92 and 96 % respectively. In vitro, T-cell proliferative response was also affected by budlein A. When murine J774 macrophages were incubated with the sesquiterpene lactone, LPS-induced IL-1β, tumor necrosis factor-α (TNF-α) and keratinocyte-derived chemokine (KC) release were concentration-dependently inhibited. In human umbilical vein endothelial cells (HUVECs), budlein A also reduced the production of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, nitrites and CAM expression elicited by LPS. Budlein A is a potent inhibitor of LPS-induced leukocyte accumulation in vivo. This effect appears to be mediated through inhibition of cytokine and chemokine release and down-regulation of CAM expression. Thus, it has potential therapeutic interest for the control of leukocyte recruitment that occurs in different inflammatory disorders.