Pharmacological Properties of Riparin IV in Models of Pain and Inflammation

Abstract

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and IV (1.56-100 mg/kg; ip) produced dose-related antinociceptive effects in the formalin test, exhibiting ED 50 values of 22.93, 114.2, 31.05 and 6.63 mg/kg, respectively. Taking the greater potency as steering parameter, riparin IV was further investigated. Riparin IV did not produce antinociceptive effect on the tail flick, suggesting that its antinociception is not a centrally-mediated action. In fact, riparin IV (1.56-25 mg/kg) produced dose-related antinociceptive and antiedematogenic effects on the complete Freund's adjuvant (CFA)-induced paw inflammation in mice. During CFA-induced inflammation, riparin IV did not modulate either the production of cytokines, TNF-α and IL-10, or COX-2 mRNA expression. On the other hand, riparin IV decreased the PGE 2 levels in the inflamed paw. In in vitro assays, riparin IV did not exhibit suppressive activities in activated macrophages. These results indicate, for the first time, that riparin IV induces antinociceptive and anti-inflammatory effects, possibly through the inhibition of prostanoid production.

Conditioned Medium of Bone Marrow-Derived Mesenchymal Stromal Cells as a Therapeutic Approach to Neuropathic Pain: A Preclinical Evaluation

“…Animal care and handling procedures were in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH, 8023) and the Institutional Animal Care and Use Committee FIOCRUZ (CPqGM 025/2011). Every effort was made to minimize the number of animals used and to avoid any discomfort [ 26 ].…”

“…The bar rotated at a constant speed of 8 revolutions per min. The animals were selected 24 h previously by eliminating those mice that did not remain on the bar for two consecutive periods of 120 s [ 26 ]. At the test day, mice from different experimental groups were placed on a rotating rod and the resistance to falling was measured up to 120 s. Mice treated with diazepam (10 mg/kg; Cristália, Itapira, Brazil), the reference drug of the test, were placed on a rotating rod 1 h after treatment.…”

“…Tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels were estimated using commercially available immunoassay ELISA kits for mice (R&D System, Minneapolis, MN, USA), according to the manufacturer's instructions. The results are expressed as picograms of cytokine per milligram of protein [ 26 ].…”

Analgesic, anti-inflammatory and immuno-modulatory effects of dezocine-propofol anesthesia combination following colonoscopy

“…Its secretion is increased in response to inflammatory reactions [14]; IL-1β is an important pro-inflammatory mediator derived from mononuclear macrophages and lymphocytes. It mediates the amplification cascade of inflammatory reactions [15,16]. The results obtained in this study indicate that before and during colonoscopy inspection, there were no significant differences in the serum contents of CRP, HSP70 and IL-1βbetween the two groups.…”

(E)-2-Cyano-3-(1H-Indol-3-yl)-N-Phenylacrylamide, a Hybrid Compound Derived from Indomethacin and Paracetamol: Design, Synthesis and Evaluation of the Anti-Inflammatory Potential

“…The paws were injected with indomethacin (50 µg/paw) 10 min before tissue retrieval to block PGE 2 production during tissue processing. The PGE 2 levels were determined by radioimmunoassay, as previously described [55]. Briefly, the plantar tissue samples were homogenized in a mixture of 3.0 mL of extraction solvent (isopropanol/ethyl acetate/0.1 N HCl, 3:3:1) and 3.0 mL of distilled water containing 20 µg/mL of indomethacin.…”