Echinodorus macrophyllus fraction with a high level of flavonoid inhibits peripheral and central mechanisms of nociception

Daniele Corrêa Fernandes; Bruna Paiva Martins; Girlaine Pereira da Silva; Eduardo Nunes da Fonseca; Shirley Vânia Moura Santos; Leosvaldo Salazar Marques Velozo; Carlos Roberto Machado Gayer; Kátia Costa de Carvalho Sabino; Marsen Garcia Pinto Coelho

doi:10.1016/j.jtcme.2021.07.001

Echinodorus macrophyllus fraction with a high level of flavonoid inhibits peripheral and central mechanisms of nociception

J Tradit Complement Med. 2021 Jul 15;12(2):123-130. doi: 10.1016/j.jtcme.2021.07.001. eCollection 2022 Mar.

Authors

Daniele Corrêa Fernandes¹, Bruna Paiva Martins¹, Girlaine Pereira da Silva¹, Eduardo Nunes da Fonseca², Shirley Vânia Moura Santos¹, Leosvaldo Salazar Marques Velozo¹, Carlos Roberto Machado Gayer¹, Kátia Costa de Carvalho Sabino¹, Marsen Garcia Pinto Coelho¹

Affiliations

¹ Department of Biochemistry and Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
² Department of Plant Biology, Institute of Biology Roberto Alcantara Gomes, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract

Background and aim: Echinodorus macrophyllus (Kunth.) Micheli is popularly used for acute and chronic inflammatory conditions. The anti-inflammatory activity was previously demonstrated for its flavonoid-enriched fractions. The aim of this work assessed the antinociceptive properties of both aqueous extract and its fractions.

Experimental procedure: The antinociceptive activity was determined by acetic acid-induced writhing, formalin test, tail immersion test, hot-plate test, xylene-induced ear edema methods, and the evaluation of its mechanism was performed in the writhing model. The aqueous extract of Echinodorus macrophyllus (AEEm) was fractionated, yielding Fr20, and Fr40. Fr40 composition was determined by HPLC-DAD-ESI-MS.

Results and conclusion: Fr20 (all doses) and Fr40 (100 mg/kg) reduced the nociception in the tail-flick model. Both fractions increased the percentage of maximum possible effect with 25 mg/kg, in the hot-plate assay, at 60 min, while AEEm reduced pain only with 50 and 100 mg/kg. There was a reduction in xylene-edema index, with Fr40 (25 mg/kg), AEEm (50 mg/kg) and Fr20 (50 mg/kg). All doses of AEEm, Fr20, and Fr40 reduced both phases of the formalin model. In the abdominal contortion model, Fr40 presented the highest activity, reducing 96% of contortions and its antinociceptive mechanism was evaluated. The results indicated the involvement of NO and adrenergic activation pathways. The main components of Fr40 are swertisin, swertiajaponin, isoorientin 7,3'-dimethyl ether, swertisin-O-rhamnoside, isoorientin, isovitexin, isovitexin-Orhamnoside, and isovitexin-7-O-glucoside. The aqueous extract of E. macrophyllus leaves and its fractions exhibited significant analgesic effect, mediated through both peripheral and central mechanisms being considered a potentially antinociceptive drug.

Keywords: 7-NI, 7-nitroindazole; AEEm, aqueous extract of E. macrophyllus; Adrenergic pathway; Chemical; DAD-UV diode array detector, ultraviolet; ESI-MS, electrospray ionization mass spectrometer; Flavonoid derivatives; Fr20, fraction isolated from EAEm on Sephadex LH-20 with 20% ethanol; Fr40, fraction isolated from EAEm on Sephadex LH-20 with 40% ethanol; GMPc, cyclic guanosine monophosphate; HPLC, high-performance liquid chromatography; HPTLC, high-performance thin-layer chromatography; MPE, percentage of the maximum possible effect; Medicinal plants; NO pathway; NO, nitric oxide; NP/PEG, natural products reagent/polyethylene glycol.; NSAIDs, nonsteroidal anti-inflammatory drugs; ODQ, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; Q-TOF, quadrupole time-of-flight; Thermal and neurogenic assays.