Anti-inflammatory and analgesic effects of the sesquiterpene lactone budlein A in mice: inhibition of cytokine production-dependent mechanism.
The anti-inflammatory activities of some medicinal plants are attributed to their contents of sesquiterpene lactones. In the present study, the anti-inflammatory and anti-nociceptive activity of a sesquiterpene lactone isolated from Viguiera robusta, budlein A in mice was investigated. The treatment with budlein A dose--(1.0-10.0 mg/kg, p.o., respectively) dependently inhibited the carrageenan-induced: i. neutrophil migration to the peritoneal cavity (2-52%), ii. neutrophil migration to the paw skin tissue (32-74%), iii. paw oedema (13-74%) and iv. mechanical hypernociception (2-58%) as well as the acetic acid-induced writhings (0-66%). Additionally, budlein A (10.0 mg/kg) treatment inhibited the mechanical hypernociception-induced by tumour necrosis factor (TNF-alpha, 36%), Keratinocyte-derived chemokine (KC, 37%) and Interleukin-1beta (IL-1beta, 28%), but not of prostaglandin E(2) or dopamine. Budlein A also inhibited the carrageenan-induced release of TNF-alpha (52%), KC (70%) and IL-1beta (59%). Furthermore, an 8 days treatment with budlein A inhibited Complete Freund's adjuvant (10 microl/paw)-induced hypernociception, paw oedema and paw skin myeloperoxidase activity increase while not affecting the motor performance or myeloperoxidase activity in the stomach. Concluding, the present data suggest that budlein A presents anti-inflammatory and antinociceptive property in mice by a mechanism dependent on inhibition of cytokines production. It supports the potential beneficial effect of orally administered budlein A in inflammatory diseases involving cytokine-mediated nociception, oedema and neutrophil migration.
Valério
Daniel A R
DA
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Avenida Bandeirantes, 3900, 14049-900-Ribeirão Preto, São Paulo, Brazil.
Cunha
Thiago M
TM
Arakawa
Nilton S
NS
Lemos
Henrique P
HP
Da Costa
Fernando B
FB
Parada
Carlos A
CA
Ferreira
Sergio H
SH
Cunha
Fernando Q
FQ
Verri
Waldiceu A
WA
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry; D001522:Behavior, Animal / Q000187:drug effects; D002351:Carrageenan / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D015232:Dinoprostone / Q000633:toxicity; D004298:Dopamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005620:Freund's Adjuvant / Q000633:toxicity; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010529:Peritoneal Cavity / Q000473:pathology; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007783:Lactones; D012717:Sesquiterpenes; C520233:budlein A; D002351:Carrageenan; D005620:Freund's Adjuvant; D015232:Dinoprostone; D004298:Dopamine