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: The fruit hull of Garcinia mangostana L. contains oxygenated and prenylated phenol derivatives, such as xanthones or xanthen-9H-ones, and is used by people in Southeast Asia as a traditional medicine for the treatment of abdominal pain, dysentery, wound infections, suppuration, and chronic ulcer. We isolated the active ingredients from the crude ethanol extract of G. mangostana L. (CEM) and investigated their analgesic effects and underlying mechanisms. CEM at intragastric (i.g.) doses of 0.5, 1, and 3 g/kg clearly exhibited antinociceptive effects in the hot-plate and acetic acid-induced writhing tests in mice. Two isolated compounds, [alpha]-mangostin and [gamma]-mangostin, exhibited analgesic effects at doses of 25 and 50 mg/kg (i.g.) in the hot-plate and formalin tests, respectively. CEM at doses of 0.5, 1, and 3 g/kg significantly inhibited xylene-induced release of inflammatory mediators. CEM, [alpha]-mangostin, and [gamma]-mangostin each dose-dependently demonstrated the ability to scavenge reactive oxygen species. In conclusion, our results demonstrate that CEM and mangostins possess potent peripheral and central antinociceptive effects in mice and suggest that xanthones may be developed as novel analgesics and anti-inflammatory drugs.

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