• Adarly Kroth, Maria do Carmo Quevedo Santos, da SilvaThaisla Cristiane BorellaTCBDepartamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Bairro Farroupilha, CEP 90050-170, Porto Alegre, RS, Brazil., SilveiraElza Maria SantosEMSDepartamento de Fisiologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Sarmento Leite, 500, Bairro Farroupilha, CEP 90050-170, Porto Alegre, RS, Brazil., Márcia Trapp, Rosângela Maria Nunes Bezzerra, Fernando Simabuco, Rivaldo Niero, and Wania Aparecida Partata.
• Área Ciências da Vida e Saúde, Universidade do Oeste de Santa Catarina, Rua Getúlio Vargas, 2125, Bairro Flor da Serra, CEP 89600-000, Joaçaba, SC, Brazil.
• J Ethnopharmacol. 2020 Jun 28; 256: 112761.

Ethnopharmacological RelevanceLuehea divaricata, popularly known in Brazil as "açoita-cavalo", has been widely explored by different ethnic groups native to Brazil to treat different pathologic conditions, including inflammatory pain. However, no report could be found on the effect that extract of L. divaricata has on neuropathic pain. This is an important topic because convergent and divergent mechanisms underlie inflammatory vs. neuropathic pain indicate that there may not always be a clear mechanistic delineation between these two conditions.Aim Of The StudyThe study aimed to determine antioxidant activity and macronutrient composition of aqueous extract from leaves of L. divaricata, and the effect of oral administration on nociception in rats with chronic constriction injury (CCI) of sciatic nerve-induced neuropathic pain, one of the most commonly employed animal models of neuropathic pain.Materials And MethodsThe antioxidant activity of the extract was evaluated by total phenolic content and DPPH, ABTS●+ and ORAC methods. Vitexin was determined by HPLC to show that the composition of the extract of the present study is similar to that used in previous studies with this genus. Total sugar and sucrose concentrations were assessed by the anthrone method, while glucose and triacilglycerides were determined using commercially available kits. Fructose concentration was calculated from values for total sugars, glucose and sucrose. Total protein was determined by Bradford assay. The effect on DNA strand breaking was investigated by inhibition of strand breaking of supercoiled DNA by hydroxyl radical. The antinociceptive effects of aqueous extract (100, 300, 500, and 1000 mg/kg, i.g.) were evaluated on thermal and mechanical thresholds for neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats. We also compared the antinociceptive effect of the extract (500 mg/kg, i.g.) with that induced by gabapentin (50 mg/kg, i.g.), a first-line clinical treatment for neuropathic pain. The effect of co-administration of extract (500 mg/kg, i.g.) and low-dose gabapentin (30 mg/kg, i.g.) was also assessed. In addition, the effect of the extract on body weight, and blood and hepatic parameters were investigated to reveal possible side effects of treatment.ResultsThe extract showed high content of total phenol; good reducing capacity for DPPH, ABTS●+ and ORAC assays; presence of vitexin; and a high capacity to inhibit strand breaking of supercoiled DNA. The predominant sugar was sucrose, followed by glucose and fructose. Total protein was greater than triacylglycerides, with the latter being present in a trace amount in the extract. The extract increased the thermal and mechanical thresholds, which was reduced by CCI. The antinociceptive effect was comparable to gabapentin and was also found after co-administration of extract and low-dose gabapentin. No significant change was found in body weight and blood and hepatic indicators after extract treatment.ConclusionsAqueous extract from L. divaricata leaves was as effective as gabapentin at attenuating CCI-induced neuropathic pain, indicating for first time the therapeutic potential of this species for this type of pain.Copyright © 2020 Elsevier B.V. All rights reserved.

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