Shikimic acid inhibits LPS-induced cellular pro-inflammatory cytokines and attenuates mechanical hyperalgesia in mice.

作者: Thallita Kelly Rabelo , Adriana Gibara Guimarães , Marlange Almeida Oliveira , Juciano Gasparotto , Mairim Russo Serafini

DOI: 10.1016/J.INTIMP.2016.07.016

关键词:

摘要: Abstract Background and aims Shikimic acid (SA) is present in a wide variety of plants microorganisms used traditional folk medicine also an essential starting material for the synthesis antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed SA-enriched products include antioxidant anti-inflammatory activities. Here, we investigated antinociceptive isolated SA. Methods RAW 264.7 macrophage cells were treated with bacterial LPS (1 μg/mL) effect SA on modulation cell viability, nitric oxide (NO) production, TNF-α, IL-1β content MAPK (ERK1/2 p38) activation was evaluated. Besides, anti-hyperalgesic vivo model mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α prostaglandin (PGE 2 ) assessed. Results In cells, suppressed LPS-induced decrease viability nitrite accumulation to control values inhibited up-regulation (65%) (39%). These effects may be mediated at least part inhibition ERK 1/2 (22%) p38 (17%) phosphorylation. mice, 50, 100, 200 mg/kg decreased formalin-induced nociceptive behavior (around 50%) inflammatory nociception PGE (50 75% each). Moreover, (100 200 mg/kg) significantly attenuated CG DA (25 40% Conclusions results indicate that presents potential development drugs treat pro-inflammatory painful conditions.

参考文章(61)
R. -R. Ji, Y. Kawasaki, Z. -Y. Zhuang, Y. -R. Wen, Y. -Q. Zhang, Protein kinases as potential targets for the treatment of pathological pain. Handbook of experimental pharmacology. ,vol. 177, pp. 359- 389 ,(2006) , 10.1007/978-3-540-33823-9_13
D. E. O'Brien, B. J. Alter, M. Satomoto, C. D. Morgan, S. Davidson, S. K. Vogt, M. E. Norman, G. B. Gereau, J. A. Demaro, G. E. Landreth, J. P. Golden, R. W. Gereau, ERK2 Alone Drives Inflammatory Pain But Cooperates with ERK1 in Sensory Neuron Survival. The Journal of Neuroscience. ,vol. 35, pp. 9491- 9507 ,(2015) , 10.1523/JNEUROSCI.4404-14.2015
Manfred Zimmermann, Ethical considerations in relation to pain in animal experimentation. Acta Physiologica Scandinavica. ,vol. 554, pp. 221- 233 ,(1986)
Adriana G Guimarães, Geovana F Oliveira, Mônica S Melo, Sócrates CH Cavalcanti, Angelo R Antoniolli, Leonardo R Bonjardim, Francilene A Silva, João Paulo A Santos, Ricardo F Rocha, José Claudio F Moreira, Adriano AS Araújo, Daniel P Gelain, Lucindo J Quintans‐Júnior, None, Bioassay‐guided Evaluation of Antioxidant and Antinociceptive Activities of Carvacrol Basic & Clinical Pharmacology & Toxicology. ,vol. 107, pp. 949- 957 ,(2010) , 10.1111/J.1742-7843.2010.00609.X
Yukinori Nagakura, Challenges in drug discovery for overcoming 'dysfunctional pain': an emerging category of chronic pain. Expert Opinion on Drug Discovery. ,vol. 10, pp. 1043- 1045 ,(2015) , 10.1517/17460441.2015.1066776
W.D. McCall, Kimberly D. Tanner, Jon D. Levine, Formalin induces biphasic activity in C-fibers in the rat Neuroscience Letters. ,vol. 208, pp. 45- 48 ,(1996) , 10.1016/0304-3940(96)12552-0
Jen-Kun Cheng, Ru-Rong Ji, Intracellular Signaling in Primary Sensory Neurons and Persistent Pain Neurochemical Research. ,vol. 33, pp. 1970- 1978 ,(2008) , 10.1007/S11064-008-9711-Z
Tomonori NAKAMURA, Emi OKUYAMA, Mikio YAMAZAKI, Neurotropic components from star anise (Illicium verum Hook. fil.) Chemical & Pharmaceutical Bulletin. ,vol. 44, pp. 1908- 1914 ,(1996) , 10.1248/CPB.44.1908
Steinar Hunskaar, Ole Bernt Fasmer, Kjell Hole, Formalin test in mice, a useful technique for evaluating mild analgesics Journal of Neuroscience Methods. ,vol. 14, pp. 69- 76 ,(1985) , 10.1016/0165-0270(85)90116-5
David Bradley, Star role for bacteria in controlling flu pandemic Nature Reviews Drug Discovery. ,vol. 4, pp. 945- 946 ,(2005) , 10.1038/NRD1917