Estudo do efeito antinociceptivo, anti-inflamatório e do perfil químico do extrato e frações dos frutos de Dillenia Indica Linn

Abstract

Dillenia indica is a tree classified as medicinal plant, belonging to the family Dilleniacea, which may also be known as elephant-apple or April-flower. The leaves, bark, stem and fruits of this plant are used in traditional medicine as a drink for the treatment of fever and cough, and an effusion is used topically in the joints for the treatment of pain and inflammation. In this work, the crude extract and its hydroalcoholic, hexane and ethyl acetate fractions were studied chemically and pharmacologically, in order to validate the popular use of this plant. The results confirmed the antinociceptive activity of the crude extract and its fractions of the fruits of D. indica observed in the formalin-induced nociception model. The administration of naloxone, an opioid receptor antagonist, inhibited the antinociceptive effect of the crude extract in the first phase of the formalin test, suggesting an effect on the opioid receptor. In addition, pretreatment with AM251, a CB1 receptor antagonist, inhibited the antinociceptive activity of the crude extract and almost all its fractions tested in the first and second phases of the formalin test, suggesting also de involvement of cannabinoid system. The chemical dereplication study by HPLC-MS-MS, supported by the GNPS platform (Global Natural Products System) led to the identification of a number of known chemical constituents in the crude extract and fractions, including flavonoids such as caffeoylmalic acid, naringenin, quercetin, caempferol, among others, which literature data corroborate the observed moderate activity, along with anti-inflammatory and analgesic activities. Therefore, the crude extract of Dillenia indica and its fractions are also constituted by flavonoids, that could be responsible by the antioxidant, in addition to the anti-inflammatory and antinociceptive activities mediated by both opioid and cannabinoid systems in mice. The fractions also showed flavonoids as constituents, that could be responsible by the antioxidant activity, and involvement of cannabinoid system in the modulation of the observed anti-inflammatory and antinociceptive activities. These results indicate that Dillenia indica could be useful in the treatment and relief of pain, confirming its traditional use as analgesic.