title: Anti-inflammatory and antinociceptive activity of epiisopiloturine, an imidazole alkaloid isolated from Pilocarpus microphyllus.
abstract: The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1β levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.
authors.affiliation: Biotechnology and Biodiversity Center Research (BIOTEC), Federal University of Piauí, Campus of Parnaíba, Avenida São Sebastião, 64202-020, Parnaíba-PI, Brazil.
authors.forename: Valdelânia G
authors.initials: VG
authors.lastname: Silva
authors.forename: Renan O
authors.initials: RO
authors.lastname: Silva
authors.forename: Samara R B
authors.initials: SR
authors.lastname: Damasceno
authors.forename: Nathalia S
authors.initials: NS
authors.lastname: Carvalho
authors.forename: Rafael S
authors.initials: RS
authors.lastname: Prudêncio
authors.forename: Karoline S
authors.initials: KS
authors.lastname: Aragão
authors.forename: Maria A
authors.initials: MA
authors.lastname: Guimarães
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Campos
authors.forename: Leiz M C
authors.initials: LM
authors.lastname: Véras
authors.forename: Markus
authors.initials: M
authors.lastname: Godejohann
authors.forename: José Roberto S A
authors.initials: JR
authors.lastname: Leite
authors.forename: André L R
authors.initials: AL
authors.lastname: Barbosa
authors.forename: Jand-Venes R
authors.initials: JV
authors.lastname: Medeiros
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000470:Alkaloids / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D001938:Brazil; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects; D010147:Pain Measurement; D009195:Peroxidase / Q000097:blood / Q000378:metabolism; D032103:Pilocarpus / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007093:Imidazoles; C575691:epiisopiloturine; D009195:Peroxidase; D015107:4-Butyrolactone