Lafoensia pacari alleviates intestinal damage by modulating cyclooxygenase-2:In silico and in vivo evaluation in a colitis model

查看全文 作　　者：Gabrielle Caroline [1]Peiter;Thayene Kamyli Moesch [2]Queiroz;Edson Luiz Michalkiewicz [3]Jr;Raphael Henrique [3]Chappuis;Jennefer Sousa [3]Luz;Luiz Henrique Casagrande [3]Piovezani;Cleison Ferreira [3]Silva;Matheus Nozomi [3]Tsutumi;Augusto Fernandes [3]Chaves;Rafael Messias [2]Luiz;Cinthia Façanha [3]Wendel;Ana Carla Zarpelon-[3]Schutz;Kádima Nayara [1]Teixeira

机构地区：[1]Programa Multicêntrico de Pós-graduação em Biquímica e Biologia Molecular-Setor Palotina,Universidade Federal do Paraná,Palotina 85.950-000,Paraná,Brazil;[2]Programa de Pós-graduação em Biotecnologia-Setor Palotina,Universidade Federal do Paraná,Palotina 85.950-000,Paraná,Brazil;[3]Campus Toledo,Universidade Federal do Paraná,Toledo 85.919-899,Paraná,Brazil

出　　处：《World Journal of Gastroenterology》索引2023年第29卷第17期,共14页

摘　　要：BACKGROUND Inflammatory bowel diseases(IBD)are a worldwide health problem and mainly affect young people,consequently affecting the workforce.Available treatments are often associated with side effects,and new therapeutic options are needed.For centuries,plants have represented important substrates in the field of drug development.Lafoensia pacari(L.pacari)is a plant whose pharmaceutical potential has been described,and may have biological activity relevant to the treatment of IBD symptoms.AIM To investigate the activity of keto-alcoholic extracts of L.pacari with respect to ameliorating the inflammatory and nociceptive symptoms of acute experimental colitis in mice.METHODS Keto-alcoholic extracts of L.pacari leaves and bark were administered to male andfemale Swiss mice weighing 25 g to 30 g(n=8 male mice and n=8 female mice).The effect of these extracts was observed in an acetic acid-induced acute experimental model of colitis with regard to antinociception/analgesia and inflammatory tissue damage.Recorded macroscopic indices included the Wallace score and the colon weight obtained using a precision scale.Mechanical hyperalgesia was determined using an electronic analgesimeter.Behavior related to overt pain was determined by quantifying the number of writhing instances within 20 min of administration of acetic acid.Molecular docking was performed using human and murine cyclooxygenase-2(COX-2)with 3 flavonoids(ellagic acid,kaempferol,and quercetin)on the AutoDock Vina software.Analysis of variance followed by Tukey’s posttest was used with P<0.05 indicating significance.RESULTS In this murine model of colitis,administration of extracts from L.pacari ameliorated acetic acidinduced writhing and colitis-associated inflammatory pain.These improvements may be attributable to the reduction in edema,inflammation(e.g.,ulcers,hyperemia,and bowel wall damage),and the intensity of abdominal hyperalgesia.The keto-alcoholic extracts of L.pacari leaves and bark administered at a dose of either 100 mg/kg or 300 mg/kg significantly reduced the number of writhing events when compared to the negative control(P<0.05).Additionally,extracts of L.pacari bark also performed better than Dipyrone.Leaf extracts administered at 10 mg/kg,30 mg/kg,and 100 mg/kg and bark extracts administered at 30 mg/kg significantly reduced or prevented the development of edema in the colon of treated mice,while mesalazine did not.Moreover,using molecular docking,we observed that the flavonoids present in L.pacari extracts bind to COX-2,an event not unique to ellagic acid.CONCLUSION The results of this study demonstrate a potential novel application of L.pacari extracts for the reduction of inflammation and promotion of antinociception/analgesia as demonstrated by our findings in a murine model of colitis.These findings were also corroborated by in silico analyses,and suggest that L.pacari extracts may be a promising therapeutic agent in the treatment of IBD. 关键词：Antinociceptive activity Anti-inflammatory activity CYCLOOXYGENASE-2 FLAVONOIDS Inflammatory bowel disease Lafoensia pacari

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Lafoensia pacari alleviates intestinal damage by modulating cyclooxygenase-2:In silico and in vivo evaluation in a colitis model

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