Antinociceptive effect of hydroalcoholic extract and isoflavone isolated from Polygala molluginifolia in mice: evidence for the involvement of opioid receptors and TRPV1 and TRPA1 channels.

PURPOSE: The plants of the genus Polygala (Polygalaceae) have been used for a long time in folk medicine to treat pain and inflammation. The species Polygala molluginifolia is native to southern Brazil and is popularly known as "cânfora". The presented study analyzes the antinociceptive effect of hydroalcoholic extract from Polygala molluginifolia (HEPm) and an isoflavone (ISO) isolated from the extract, in behavioral models of pain in mice, as well as the mechanism underlying this effect. MATERIALS AND METHODS: The phytochemical analysis of HEPm was performed through a capillary electrophoresis analysis and colorimetric test. The antinociceptive effects of HEPm and ISO (10-1000 mg/kg, i.g.) were evaluated by applying the formalin test; mechanical and thermal hyperalgesia to postoperative pain in mice. The possible involvement of opioid receptors, TRPV1 and TRPA1 channels in the antinociceptive effect of HEPm and ISO were also evaluated. Finally, the nonspecific effects of HEPm and ISO were evaluated by measuring locomotor activity (Open-field Test) and corporal temperature. RESULTS: The 5,3',4'-trihydroxy-6″,6″-dimethylpyrano[2″,3″:7,6] isoflavone (ISO) was identified in HEPm by capillary electrophoresis analysis and selected for the experimental tests. The oral administration of HEPm or of ISO significantly inhibited the neurogenic and inflammatory phases of formalin-induced pain, edema formation and local hyperemia, without causing any change to locomotor activity. Acute and repeated treatment of animals with HEPm reduced mechanical and thermal (heat and cold) hyperalgesia in the postoperative pain. In addition, administering HEPm or ISO markedly reduced nociceptive behavior induced by the peripheral and central injection of TRPV1 and TRPA1 channels activators. Finally, the antinociception provided by the administration of HEPm or ISO was reversed by the preadministration of naloxone. CONCLUSIONS: Taken together, these results provide the first experimental evidence of the significant antinociceptive effect of HEPm and ISO in animal models of acute pain without causing sedation or locomotor dysfunction. This effect appears to be mediated, at least in part, by the activation of opioid receptors and/or by the inhibition of TRPV1 and TRPA1 channels. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant Polygala molluginifolia in the development of phytomedicines with analgesic properties.

Oleaginous extract from the fruits Pterodon pubescens Benth induces antinociception in animal models of acute and chronic pain.

ETHNOPHARMACOLOGICAL RELEVANCE: Pterodon pubescens Benth is a medicinal plant commonly used for therapeutic purposes in folk medicine for rheumatic diseases' treatment. In the present work we analyzed the chemical composition of the oleaginous extract of P. pubescens Benth (OEPp) and extended the antinociceptive effect of OEPp evaluating its role on animal models of acute and chronic pain. MATERIALS AND METHODS: The antinociceptive and antiedematogenic effects of OEPp (3-100mg/kg, i.g.) were evaluated in the formalin test; mechanical allodynia in the postoperative pain and complex regional pain syndrome type-I (CRPS-I) animal models; and thermal hyperalgesia was induced by plantar incision. Finally, we performed a phytochemical analysis of OEPp. RESULTS: The chemical composition of OEPp was analyzed by mass spectrometry (GC/MS) and eight sesquiterpene compounds were identified, i.e. three major sesquiterpene (E-cariofilene, γ-muurolene, biciclogermacrene), and nine vouacapane diterpenes, four of which showed in major concentration (6α-acetoxyvouacapane, 6α,7ß-dimetoxivouacapan-17-ene, 6α-acetoxy,7ß-hidroxyvouacapane, 6α,7ß-diacetoxycouacapane). Furthermore, the results of the present study demonstrate, for the first time, that the OEPp reduced mechanical allodynia in the postoperative pain and CRPS-I animal models. OEPp also increased the paw withdrawal latency in hot- and cold-plate tests in the postoperative pain model. In addition, the present work confirms and extends previous data from literature showing that systemic administration of OEPp caused significant inhibition against both phases of pain response to formalin intraplantar injection and edema formation. CONCLUSIONS: Together, present and previous findings show that OEPp given intra-gastrically caused significant inhibition against both phases of formalin intraplantar injection and effectively inhibited mechanical and thermal hyperalgesia in the postoperative pain and CRPS-I animal models.