Budlein A from Viguiera robusta inhibits leukocyte-endothelial cell interactions, adhesion molecule expression and inflammatory mediators release.
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-1beta, tumor necrosis factor-alpha (TNF-alpha) 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-alpha, 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.
Nicolete
Roberto
R
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14040-903 Ribeirão Preto, Brazil.
Arakawa
Nilton S
NS
Rius
Cristina
C
Nomizo
Auro
A
Jose
Peter J
PJ
Da Costa
Fernando B
FB
Sanz
María-Jesús
MJ
Faccioli
Lúcia H
LH
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D003907:Dexamethasone; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000302:isolation & purification*; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D036904:Leukocyte Rolling / Q000187:drug effects*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects
D015815:Cell Adhesion Molecules; D018925:Chemokines; D007166:Immunosuppressive Agents; D007783:Lactones; D008070:Lipopolysaccharides; D009573:Nitrites; D010936:Plant Extracts; D012717:Sesquiterpenes; C520233:budlein A; D009569:Nitric Oxide; D003907:Dexamethasone