LASSBio-1586, an N-acylhydrazone derivative, attenuates nociceptive behavior and the inflammatory response in mice

Abstract

Pain and inflammation are complex clinical conditions that are present in a wide variety of disorders. Most drugs used to treat pain and inflammation have potential side effects, which makes it necessary to search for new sources of bioactive molecules. In this paper, we describe the ability of LASSBio-1586, an N-acylhydrazone derivative, to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In these experimental models, LASSBio-1586 significantly (p<0.05) reduced nociceptive behavior. Several methods of acute and chronic inflammation induced by different chemical (carrageenan, histamine, croton oil, arachidonic acid) and physical (cotton pellet) agents were used to evaluate the anti-inflammatory effect of LASSBio-1586. LASSBio-1586 exhibited potent anti-inflammatory activity in all tests (p<0.05). Study of the mechanism of action demonstrated the possible involvement of the nitrergic, serotonergic and histamine signaling pathways. In addition, a molecular docking study was performed, indicating that LASSBio-1586 is able to block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. In summary, LASSBio-1586 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Anti-inflammatory potential of dichloromethane leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in mice

“…These two enzymes catalyze the synthesis of prostaglandins, which stimulate inflammation. The NSAIDs blocks the cyclooxygenase enzymes and decrease prostaglandin levels in the entire body, leading to a reduction of inflammation 26 , 27 .…”

Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice

“…Mice were kept in groups of six individuals (n = 6) in polypropylene cages at room temperature set at 22 ± 1°C with a relative humidity of 60–80%, light/dark cycle of 12 h (start 06:00 and end 18:00), and water and food (Purina Labina) ad libitum . This work was developed according to the Conselho Nacional para o Controle de Experimentação Animal (CONCEA, Brazil) and implemented following the recommendations of the International Association for the Study of Pain [ 13 , 14 ]. All experimental procedures were accredited by the Comitê de Ética no Uso de Animais of the Universidade Federal do Vale do São Francisco (CEUA-UNIVASF, Brazil) under the authorization number 0004/241017.…”

“…After each protocol, mice were anesthetized with an injection of 60 mg/kg of ketamine associated with 7.5 mg/kg of xylazine, intraperitoneally, followed by cervical dislocation. Syringes of 1 ml with a needle of 13 x 0.45 mm were used for intraperitoneal injections whereas a gavage needle was used for the oral route administrations [ 14 ].…”

“…For the initial screenings, we chose the writhing test as a model to evaluate the analgesic effect of the hydrazone derivatives [ 14 , 15 ]. The referred test was performed as described by Collier and collaborators [ 14 , 16 ] with minor adjustments. To perform it, mice were split into thirteen groups of six animals each (n = 78), being treated orally (p.o.)…”

“…or saline (negative control, p.o.) 1 h before the nociceptive agent (10 ml/kg of a 0.9% acetic acid solution) [ 14 , 17 ]. After five minutes of the acetic acid injection, the number of abdominal writhing was recorded for 10 min [ 14 , 18 ].…”