Improvement of p-cymene antinociceptive and anti-inflammatory effects by inclusion in β-cyclodextrin.
Previously, we have demonstrated the analgesic-like property of p-cymene in rodents. Short half-life is a limitation for p-cymene application and several approaches have been used to improve pharmaceutical properties of monoterpenes, including the employment of drug-delivery systems. Here, we used p-cymene/β-cyclodextrin (β-CD) complex and p-cymene (PC) isolated to evaluated whether the complex formulation is able to improve the antinociceptive activity of this monoterpene. Male mice (26-30g) were pretreated with PC/β-CD (20 or 40mg/kg, p.o.), PC (20 or 40mg/kg, p.o.) or vehicle (distilled water), 0.5h before painful tests and antinociceptive effect was evaluated at times: 0.5, 1, 2, 4, 8, and 16h after treatment. We evaluated the analgesic-like effect of PC/β-CD and PC in acetic acid-induced abdominal writhes, hot-plate, carrageenan-induced paw edema and in rota-rod apparatus. Our results demonstrated that acute treatment with complex PC/β-CD produced an antinocicepitve effect (p<0.01 or p<0.001) for 8h followed whereas isolated PC produced the same effect for 2h. Similar results were obtained in hot-plate test, PC/β-CD, in all doses, significantly reduces (p<0.01 or p<0.001) nociceptive behavior for 8h while isolated PC for 1h, did so only in higher dose. Such results were unlikely to be caused by motor abnormality. Systemic pretreatment with PC/β-CD and PC inhibited the development paw edema by carrageenan 1%, but PC/β-CD did so during a longer period when compared with isolated monoterpene alone. Our results provide evidence to propose that the complex with β-CD improved analgesic and anti-inflammatory effects of p-cymene.
Departamento de Fisiologia da Universidade Federal de Sergipe (DFS/UFS), Aracaju-SE, Brazil.
Jullyana de Souza Siqueira
Jde S
Quintans
Paula Passos
PP
Menezes
Márcio Roberto Viana
MR
Santos
Leonardo Rigoldi
LR
Bonjardim
Jackson Roberto Guedes Silva
JR
Almeida
Daniel Pens
DP
Gelain
Adriano Antunes de Souza
AA
Araújo
Lucindo José
LJ
Quintans-Júnior
D019342:Acetic Acid / Q000009:adverse effects; D000700:Analgesics / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D001522:Behavior, Animal; D002351:Carrageenan / Q000494:pharmacology; D000081007:Cymenes; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D006358:Hot Temperature; D046911:Macromolecular Substances / Q000737:chemistry; D008297:Male; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D010147:Pain Measurement / Q000379:methods; D008517:Phytotherapy; D013997:Time Factors; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000627:therapeutic use*
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000081007:Cymenes; D046911:Macromolecular Substances; D039821:Monoterpenes; D047392:beta-Cyclodextrins; C007210:4-cymene; D002351:Carrageenan; D019342:Acetic Acid