Analysis of the anti-inflammatory and chemopreventive potential and description of the antimutagenic mode of action of the Annona crassiflora methanolic extract

作者:Rocha Roberta Schroder; Leite Kassuya Candida Aparecida; Nazari Formagio Anelise Samara; Mauro Mariana de Oliveira; Andrade Silva Magaiver; Duenhas Monreal Antonio Carlos; Cunha Laura Andrea Luiza; Vieira Maria do Carmo; Oliveira Rodrigo Juliano*
来源:Pharmaceutical Biology, 2016, 54(1): 35-47.
DOI:10.3109/13880209.2015.1014567

摘要

Context: Annona crassiflora Mart. (Annonaceae) is a medicinal plant that is widely used in folk medicine, which leads to its investigation as a potential source of new pharmacological principles.Objective: This study describes the anti-inflammatory, antiallodynic, and antimutagenic/chemopreventive activities of the leaves A. crassiflora methanolic extract. Its antimutagenic mode of action was analyzed in a plant or animal experimental model.Materials and methods: Total flavonoids were quantified by spectrophotometry at 415nm and its composition was analyzed by H-1 NMR spectra. Animals received orally, 30, 100, and 300mg/kg of extract in both tests, carrageenan-induced paw edema and myeloperoxidase activity. Animals were treated with 100 and 300mg/kg, in all the analyzed tests, pleural cell migration and protein exudation, carrageenan-induced cell migration into the pouch, induction of joint inflammation and carrageenan-induced allodynia response in the mouse paw. To evaluate the antimutagenic/chemopreventive activity through the Allium cepa test, we used 5, 10, and 15mg/L of extract, and for the micronucleus test in the peripheral blood, we used the dose of 15mg/kg.Results: The fractionation of the ethyl acetate (EA) fraction, resulting from the partition of the methanol extract of the A. crassiflora, afforded through chromatographic methods resulted in the isolation of kaempferol 3-O--glucoside and kaempferol 3-O--diglucoside. Oral treatment with 100 and 300mg/kg of extract significantly inhibited the carrageenan-induced edema formation, with inhibitions of 537% and 47 +/- 10%; in MPO activity, the observed inhibitions were 60 +/- 7% for 100mg/kg treatment and 63 +/- 7% for 300mg/kg. The ACME reduced significantly the total leukocytes (an inhibition of 78 +/- 9% with 100mg/kg and 90 +/- 7% with 300mg/kg) and protein levels (approximately 100% inhibition with both doses) in the pleurisy model. Incarrageenan-induced leukocyte migration into the pouch, the extract inhibited leukocyte migration only when administered 300mg/kg per dose (the reduction was 43 +/- 5%). Pretreatment with extract failed to reduce the zymosan-induced edema formation and did not inhibit the carrageenan-induced mechanical allodynia. Damage reduction in Allium cepa tested with different concentrations (5, 10, and 15mg/L) was 66.17, 75.75, and 69.19% for the pre-treatment; 72.72, 33.33, and 22.22% for the simple simultaneous treatment; 100.50, 93.93, and 102.52% for the simultaneous treatment with pre-incubation; 89.39, 79.79, and 84.34%; for the post-treatment, and 86.36, 81.31, and 93.43% for the continuous treatment. The antimutagenic evaluation in the micronucleous test showed a damage reduction of 75.00 and 64.58% for the pre-treatment and simultaneous protocols, respectively. The post-treatment protocol increased the cyclophosphamide effects in 45.83%.Conclusion: These results suggest that this medicinal plant has chemopreventive and anti-inflammatory therapeutic potential.

  • 出版日期2016-1-2