Anti-inflammatory and antinociceptive activities of LQFM002 - A 4-nerolidylcatechol derivative.

AIMS: The current study describes the synthesis and pharmacological evaluation of (E)-N-(3,7-dimethylocta-2,6-dienyl)-1,3-dimethyl-1H-pyrazol-5-amine (LQFM002), a compound originally designed through a molecular simplification strategy from 4-nerolidylcatechol. LQFM002 was evaluated for preservation of the PLA(2) enzyme inhibitory effects of the lead compound, 4-nerolidylcatechol, using in vitro and in vivo models. MAIN METHODS: Rota-rod, open field and pentobarbital-induced sleeping tests were used to evaluate the effects of LQFM002 on the central nervous system. A gel plate assay of PLA(2) activity, carrageenan-induced pleurisy and TNF-α levels was used to assay anti-inflammatory activity. Antinociceptive activities of LQFM002 were evaluated with acetic acid-induced writhing, formalin and hot-plate tests, while involvement of the opioid pathway in the LQFM002 antinociceptive effect was investigated with naloxone pre-treatment. KEY FINDINGS: LQFM002 inhibited PLA(2) activity, cell migration into the pleural cavity, and capillary permeability (Evan's blue concentration) and reduced TNF-α levels in pleural exudates. LQFM002 also reduced acetic acid-induced writhing and the licking time in both phases of the formalin test and increased latency in the hot-plate test. Pre-treatment with 8.25 µmol/kg naloxone (3mg/kg) reversed the analgesic effects of LQFM002 in the early phase of the formalin test. SIGNIFICANCE: LQFM002 showed anti-inflammatory activity, which possibly involved reduction of leukocyte migration and TNF-α levels. LQFM002 also demonstrated inhibition of PLA(2) activity in vitro. LQFM002 had an antinociceptive effect that involved the opioidergic system.

Antidepressant-like effect of Lafoensia pacari A. St.-Hil. ethanolic extract and fractions in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Lafoensia pacari A. St.-Hil. (Lythraceae) has been referred in Brazilian traditional medicine for the treatment of different diseases, among them depression. Nevertheless, there are not studies about this possible effect on the central nervous system (CNS). AIM OF THE STUDY: To evaluate the antidepressant-like effects of the ethanolic extract of Lafoensia pacari (PEtExt) and its fractions on the performance of male mice. MATERIALS AND METHODS: Antidepressant activity was studied using forced swimming (FST) and tail suspension (TST) tests, and motor activity in the open-field test. The ethanolic extract of Lafoensia pacari (PEtExt) were administered acutely (1.0 g/kg, p.o.), for 21 days (100, 300 mg, and 1.0 g/(kg day), p.o.), three administration in a 24-h period (1.0 g/kg, p.o.), and the fractions for 21 days. Imipramine (15 mg/(kg day), p.o.) was used as the control positive. RESULTS: The PEtExt significantly reduced immobility time in FST and TST, without affecting the motor activity. Only the chloroformic fraction (50 mg/(kg day), p.o.) increase the latency to immobility and decrease the immobility time in the FST. CONCLUSIONS: These data indicate that the extract of Lafoensia pacari A. St.-Hil. possesses antidepressant-like properties in mice.