Seeking to develop a new analgesic phytomedicine, a spray-dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2′′-O-rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan-induced mechanical hypernociception, with an ID50% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund's adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)-induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2′′-O-rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2′′-O-rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids.
The study analyzes the chemical composition of the essential oil obtained from the leaves of Ugni myricoides (Kunth) O. Berg (U. myricoides EO). The composition of the essential oil was characterized by GC-FID and GC-MS analysis, showing at least six major constituents: α-pinene (52.1%), 1,8-cineole (11.9%), α-humulene (4.6%), caryophyllene oxide + globulol (4.5%), humulene epoxide II (4.2%) and β-caryophyllene (2.9%). It demonstrates for the first time the systemic anti-hypernociceptive properties of this orally administered oil in inflammatory and neuropathic models of hypernociception in mice. The effects of U. myricoides EO and its major constituent, α-pinene, were compared with those of indomethacin or gabapentin, drugs used clinically to treat inflammatory and neuropathic processes. Like indomethacin (5 or 10 mg/kg, p.o.), U. myricoides EO (5-50 mg/kg, p.o.) was able to significantly prevent mechanical hypernociception induced by carrageenan or complete Freund's adjuvant (CFA) in mice. These effects were observed for up to 48 h after i.pl. injection of flogistic agents. Repeated treatment with U. myricoides EO (5-25 mg/kg, p.o.), α-pinene (5-50 mg/kg, p.o.), or gabapentin (70 mg/kg, p.o.) also abolished the mechanical sensitization induced by CFA, or following the partial ligation of the sciatic nerve (PLSN). The present results indicate that U. myricoides EO produces marked anti-hypernociceptive effects in carrageenan and CFA mechanical sensitization models, and also inhibited neuropathic pain-like behavior after PLSN with efficacy similar to that observed for indomethacin or gabapentin. The relevant effects shown by U. myricoides EO are related, at least in part, to the presence of α-pinene and may be of potential interest for the management of inflammatory and neuropathic pain.
These results provide strong evidence that NA-3,4-DCM produces antihypernociception in mice at peripheral, spinal, and supraspinal sites, and that interaction with the group I metabotropic glutamate receptors and NMDA receptors contributes to the mechanisms underlying its effect.
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