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.

Anti-migraine effect of Areca Catechu L. nut extract in bradykinin-induced plasma protein extravasation and vocalization in rats

“…The anti-migraine effect of ANE is probably through its action on bradykinin receptors (B1 or B2) and inhibiting PPE and vocalization in rats. As the alkaloids from other plant shown to be effective in inhibiting bradykinin receptors (Silva et al, 2013), the observed protective effect could be via antagonism of bradykinin receptors by alkaloids from ANE. Thus the alkaloids from ANE might possess the anti-migraine potential and could be the future specific target molecule for evaluation of anti-migraine properties.…”

Analgesic and anti-inflammatory activity of crude leaf and bark extract of Lantana Camara

“…was injected to the positive and negative control groups. After acetic acid administration, for 20 min the number of writhes was counted [22,23]. The extracts and acetylsalicylic acid suspended in tween 80 prior to administration and given orally.…”

Imidazole alkaloids inhibit the pro-inflammatory mechanisms of human neutrophil and exhibit anti-inflammatory properties in vivo

“…Anti‐inflammatory and antinociceptive activities were evaluated in acute inflammation and nociception models (1 mg/kg, i.p.) such as carrageenan‐induced paw oedema, acetic acid‐induced writhing, hot plate and the formalin tests in mice . The antinociceptive effect of EPI seems to be partially mediated by the activation of the opioid receptors, while the anti‐inflammatory effect occurred by the reduction in the paw oedema and decrease in leucocyte migration, and TNF‐α and IL‐1β levels in the peritoneal cavity .…”