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Anti-nociceptive effect of total alkaloids isolated from the seeds of Areca catechu L (Arecaceae) in mice Zhao, Lei; Li, Yu; Yang, Shaohui; Zhang, Pei & Wang, Jing Abstract Purpose: To investigate the antinociceptive effect of the total alkaloids (TA) isolated from the seeds of Areca catechu L. (SAC) and to elucidate the probable mechanism of action. Methods: TA extraction conditions including concentration of ethanol, extraction temperature, liquid– solid ratio and designed pH were optimized by an orthogonal experiment {L9(3)4} test. The anti-nociceptive effect of the extract in mice was evaluated by acetic acid writhing reflex test, hot plate test, capsaicin-induced nociception test, tail-flick test and formalin-induced pain test in mice. Furthermore, pretreatment of the animals with naloxone (2 mg/kg) was performed to investigate whether the anti-nociceptive effect involved the opioid route or not. The locomotor activity of TA in mice were also assessed. Results: The optimum extraction conditions of TA were as follows: solid-liquid ratio of 1: 15 (w/v), ethanol concentration of 80 %, pH of 9.0 and extraction temperature of 70 °C. Oral administration of TA produced a marked anti-nociceptive activity in mice, and pretreatment with naloxone did not reverse the anti-nociceptive activity of TA in mice. Also, the locomotor activity of mice was not affected by TA. In addition, TA significantly down-regulated the expression levels of COX-2 in the dorsal root of mice spinal cord at 100, 200 and 400 mg/kg doses. Conclusion: The results demonstrate that TA possesses significant anti-nociceptive effects, and the mechanisms are closely related to suppression of COX-2 expression. Overall, the results provided scientific support for the use of TA in treatment of pain. Keywords Areca catechu; Total alkaloids; Anti-nociceptive; Formalin-induced pain; Naloxone

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