Antinociceptive Effect of the Essential Oil of Schinus terebinthifolius (female) Leaves on Adult Zebrafish (Danio rerio).

Schinus terebinthifolius Raddi (Anacardiaceae) is popularly known in Brazil as aroeira-da-praia and has pharmacological use as an astringent, antidiarrheal, anti-inflammatory, depurative, diuretic, and antifebrile agent. Although the neuropathic antinociceptive potential of S. terebinthifolius fruits has already been investigated, this study is the first one to analyze the acute antinociceptive effect of the essential oil of S. terebinthifolius (female) leaves (EOFSt) on adult zebrafish. EOFSt was submitted to antioxidant activity evaluation by two methods (ferrous ion-chelating capacity [FIC] and ß-carotene). The animals (n = 6/group) were treated orally (20 µL) with EOFSt (0.1, 0.5, or 1.0 mg/mL) or vehicle (0.9% sodium chloride [NaCl]; 20 µL), and submitted to nociception (formalin, cinnamaldehyde, capsaicin, glutamate, acidic saline, and hypertonic saline). Possible neuromodulation mechanisms, as well motor alterations and toxicity were also evaluated. In the FIC assay, EOFSt showed ferrous ion-chelating capacity in ∼40% to 90%. Regarding the ß-carotene bleaching assay, EOFSt showed inhibition in a 58% to 80% range. Oral administration of EOFSt showed no acute toxicity and did not alter the locomotor system of aZF, and reduced the nociceptive behavior in all tested models. These effects of EOFSt were significantly similar to those of morphine, used as a positive control. The antinociceptive effect of EOFSt was inhibited by naloxone, L-NAME, ketamine, camphor, ruthenium red, and amiloride. The antinociceptive effect of the EOFSt cornea was inhibited by capsazepine. EOFSt has the pharmacological potential for acute pain treatment and this effect is modulated by the opioid system, NMDA receptors, and transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid 1 (TRPV1), and acid-sensing ion channels. The EOFSt also has the pharmacological potential for corneal pain treatment and this effect is modulated by the TRPV1 channel.

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).

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.

Orofacial antinociceptive effect of Mimosa tenuiflora (Willd.) Poiret.

Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles.