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Antinociceptive activity of ethanolic extract of Azadirachta indica A. Juss (Neem, Meliaceae) fruit through opioid, glutamatergic and acid-sensitive ion pathways in adult zebrafish (Danio rerio)

2018; Elsevier BV; Volume: 108; Linguagem: Inglês

10.1016/j.biopha.2018.08.160

1950-6007

Francisco Lucas Alves Batista, Luiza Michelly Gonçalves Lima, Izamar A. Abrante, José Ismael Feitosa de Araújo, Francisca Leidivânia Alves Batista, Izabel A. Abrante, Erlândia A. Magalhães, Daniele R. Lima, Maria da Conceição L. Lima, Brenda Silva do Prado, Luiz Francisco Wemmenson Gonçalves Moura, Maria Izabel Florindo Guedes, Maria Kueirislene Amâncio Ferreira, Jane Eire Silva Alencar de Menezes, Sacha Aubrey Alves Rodrigues Santos, Francisco Rogênio da Silva Mendes, Renato de Azevedo Moreira, Ana Cristina de Oliveira Monteiro‐Moreira, Adriana Rolim Campos, Francisco Ernani Alves Magalhães,

Pain Mechanisms and Treatments

Neem fruit (Azadirachta indica A. Juss.) are popularly used to treat infections, diarrhea, fever, bronchitis, skin diseases, infected burns and hypertension. Although the antinociceptive and anti-inflammatory potential of A. indica has already been investigated in experimental models of pain and inflammation in mice, the current research is the first to report the evaluation of the capacity of A. indica fruit ethanolic extract (EtFrNeem) in acute pain attenuation using the adult zebrafish (Danio rerio) as an alternative model to the use in rodents. EtFrNeem was submitted to antioxidant action, preliminary chemical prospecting, FT-IR and determination of phenol and flavonoid content tests. Subsequently, EtFrNeem was tested for acute nociception and abdominal inflammation, locomotor activity, and acute toxicity in adult zebrafish. Possible neuromodulation mechanisms were also evaluated. EtFrNeem showed low antioxidant activity, but was shown to be rich in flavonoids. EtFrNeem showed no anti-inflammatory action, did not alter the locomotor system, and it was not toxic. However, EtFrNeem significantly reduced the nociceptive behavior induced by formalin, glutamate and acidic saline, when compared to the control group. These effects of EtFrNeem were significantly similar to those of morphine, used as a positive control. The antinociceptive effect of EtFrNeem was inhibited by naloxone, ketamine and amiloride. EtFrNeem has the pharmacological potential for acute pain treatment and this effect is modulated by the opioid system, NMDA receptors and ASICs channels. These results lead us to studies of isolation and characterization of EtFrNeem bioactive principles, using adult zebrafish as an experimental model.