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 ED50 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 PGE2 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.
Highlights
Inflammation is a body’s protective response to infection, tissue injury and other noxious conditions.On the other hand, the outcome may be deleterious if it leads to chronic inflammation, which stimulates the development of many diseases, such as atherosclerosis, diabetes, neurodegenerative diseases and cancer [1]
Of for the first time, that riparin IV possesses antinociceptive and anti-inflammatory described effects deprived for the first time, that riparin possesses antinociceptive and anti-inflammatory effects deprived immunosuppressive action, possibly related to its ability to inhibit the production of PGE2 . of immunosuppressive action, possibly related to its ability to inhibit the production of PGE2
Under the same conditions, (40 μM) was able to reduce the levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and IL-6 (p < 0.05), while dexamethasone (40 μM) was able to reduce the levels of pro-inflammatory cytokines, TNF-α and IL-6 enhanced the anti-inflammatory cytokine IL-10 (p < 0.01) in activated macrophages. These results demonstrated that inhibition of NO and pro-inflammatory cytokines by activated macrophage is not a mechanism involved in the anti-inflammatory effect of riparin IV
Summary
Inflammation is a body’s protective response to infection, tissue injury and other noxious conditions. Its anti-inflammatory activities in preclinical studies [14,15,16,17,18] These properties awakened interest in verifying natural alkaloids, known as riparins, showed antimicrobial, anxiolytic, antinociceptive and antithe pharmacological potential of these amides, which can be obtained synthetically by condensation inflammatory activities in preclinical studies [14,15,16,17,18]. These properties awakened interest in verifying between acyl chlorides and. Of for the first time, that riparin IV possesses antinociceptive and anti-inflammatory described effects deprived for the first time, that riparin possesses antinociceptive and anti-inflammatory effects deprived immunosuppressive action, possibly related to its ability to inhibit the production of PGE2 . of immunosuppressive action, possibly related to its ability to inhibit the production of PGE2
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
