Synergistic effect of the interaction between curcumin and diclofenac on the formalin test in rats |
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| Institution: | 1. Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México, DF, Mexico;2. Área Académica de Medicina del Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico;3. Universidad del Fútbol y Ciencias del Deporte, San Agustín Tlaxiaca, Hidalgo, Mexico;4. Laboratorio de Farmacología, Sección de Estudios Posgrado e Investigación. Escuela Nacional de Medicina y Homeopatía Instituto Politécnico Nacional, México, DF, Mexico;1. Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Dübendorf 8600, Switzerland;2. EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne 1015, Switzerland;3. ETHZ, Institute of Biogeochemistry and Pollutant Dynamics, Zürich 8092, Switzerland;1. Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore, Singapore;2. Immunology Program, Life Science Institute; National University of Singapore, Singapore, Singapore;1. Department of Anatomy, College of Medicine, Kyungpook National University, Daegu 700-422, South Korea;2. Aquaculture Management Division, National Fisheries Research and Development Institute, Busan 619-705, South Korea;3. Laboratory of Cell and Developmental Signaling, National Cancer Institute-Frederick, Frederick, MD 21702, USA;4. Department of Pharmacology, College of Medicine, Kyungpook National University, Daegu 700-422, South Korea;5. ABRC, School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu 702-701, South Korea;1. Reproductive Biology and Toxicology Laboratory, UNESCO Satellite Center of Trace Element Research & School of Studies in Zoology, Jiwaji University, Gwalior, Madhya Pradesh, India;2. Department of Zoology, DDU Gorakhpur University, Gorakhpur, Uttar Pradesh, India;3. School of Pharmacy and Technology Management (SPTM), Shri Vile Parle Kelavani Mandal’s (SVKM''s),Narsee Monjee Institute of Management Studies (NMIMS), Mukesh Patel Technology Park, Babulde, Bank of Tapi River, Mumbai-Agra Road, Shirpur, Dist. Dhule-India;1. Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA;2. College of Pharmacy/Division of Medicinal Chemistry and Pharmacognosy, The Ohio State University, 434 Parks Hall, 500 W 12th Avenue, Columbus, OH 43210, USA |
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| Abstract: | The association of non-steroidal anti-inflammatory drugs with certain plant extracts can increase antinociceptive activity, permitting the use of lower doses and thus limiting side effects. Therefore, the aim objective of the current study was to examine the effects of curcumin on the nociception and pharmacokinetics of diclofenac in rats. Antinociception was assessed using the formalin test. Diluted formalin was injected subcutaneously into the dorsal surface of the right hind paw. Nociceptive behavior was quantified as the number of flinches of the injected paw during 60 min after injection, and a reduction in formalin-induced flinching was interpreted as an antinociceptive response. Rats were treated with oral diclofenac (1–31 mg/kg), curcumin (3.1–100 mg/kg) or the diclofenac–curcumin combination (2.4–38.4 mg/kg). To determine the possibility of a pharmacokinetic interaction, the oral bioavailability of diclofenac (10 mg/kg) was studied in presence and the absence of curcumin (31 mg/kg). Diclofenac, curcumin, or diclofenac–curcumin combination produced an antinociceptive effect on the formalin test. ED30 values were estimated for the individual drugs, and an isobologram was constructed. The derived theoretical ED30 for the antinociceptive effect (19.2 mg/kg) was significantly different from the observed experimental ED30 value (9.8 mg/kg); hence, the interaction between diclofenac and curcumin that mediates the antinociceptive effect was synergistic. Notwithstanding, the interaction does not appear to involve pharmacokinetic mechanisms, as oral curcumin failed to produce any significant alteration in oral diclofenac bioavailability. Data suggest that the diclofenac–curcumin combination can interact at the systemic level and may have therapeutic advantages for the clinical treatment of inflammatory pain. |
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| Keywords: | Curcumin Diclofenac Synergism Nociception Rats Pharmacokinetic |
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