Agrimonia pilosa Ledeb. produces an antinociceptive effect in ICR mice in both chemically\ninduced and thermal pain models. In the present study, we examined the antinociceptive\neffects of single components isolated from Agrimonia pilosa Ledeb. (AP) extract in ICR mice.\nThree active compounds isolated from AP, including rutin, luteolin-7-O-glucuronide, and\napigenin-7-O-glucuronide, were isolated and identified by comparing EI-MS, 1H-, 13C-NMR,\nand UV. We studied the antinociceptive effects of three single components administered orally\nat doses of 10 and 20 mg/kg in monosodium urate (MSU)-treated pain model as measured\nby von Frey test. Among these compounds, apigenin-7-O-glucuronide was more effective in\nthe production of antinociceptive effects. We further characterized the antinociceptive effects\nand possible mechanisms of apigenin-7-O-glucuronide in writhing and formalin tests. Oral\nadministration of Apigenin-7-O-glucuronide caused a reduction in the number of writhing and\neffectively reduced the pain behavior observed during the second phase of the formalin test in\na dose-dependent manner. In addition, the pretreatment of yohimbine instead of naloxone or\nmethysergide attenuated apigenin-7-O-glucuronide-induced antinociception in the writhing test.\nMoreover, apigenin-7-O-glucuronide caused reduction in the expression of p-P38, p-CREB, and\np-mTOR induced by formalin injection. Our results indicate that apigenin-7-O-glucuronide shows an\nantinociceptive effect in various pain models. In addition, spinal alpha2-adrenergic receptors appear to\nbe involved in the production of antinociception induced by apigenin-7-O-glucuronide. Furthermore,\nthe antinociceptive effect of apigenin-7-O-glucuronide appears to be mediated by reduction in the\nexpression of p-P38, p-CREB and p-mTOR levels in the spinal cord.
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