Cycloartanes from Oxyanthus pallidus and derivatives with analgesic activities

BACKGROUND: The leaves of Oxyanthus pallidus Hiern (Rubiaceae) are extensively used in the west region of Cameroon as analgesic. These leaves are rich in cycloartanes, a subclass of triterpenes known to possess analgesic and anti-inflammatory properties. The present study aimed at evaluating the analgesic properties of three cycloartanes isolated from Oxyanthus pallidus leaves as well as their aglycones and acetylated derivatives. METHODS: Three cycloartanes OP(3), OP(5) and OP(6) obtained by successive chromatography of the crude methanol extract of the leaves were hydrolysed to yield respective aglycone AOP(1), AOP(2), AOP(3) and acetylated to HOP(1), HOP(2) and HOP(3) respectively. Formalin-induced pain model was used to evaluate the acute anti-nociceptive properties of these cycloartanes (5 mg/kg, p.o) in mice and to determine the structure-activity relationship. Acute (24 h) and chronic (10 days) anti-hyperalgesic and anti-inflammatory activities of OP(5) were evaluated at the doses of 2.5 and 5 mg/kg/day administered orally. OP(6) was also evaluated in acute experiments. The antioxidant and hepato-protective activities of OP(5) were evaluated at the end of the chronic treatment. RESULTS: The mixture and the individual isolated cycloartanes significantly inhibited both phases of formalin-induced pain with percentage inhibition ranging from 13 to 78 %. Acid hydrolysis did not significantly affect their antinociceptive activities while acetylation significantly reduced the effects of these compounds during the second phase of pain. OP(5) and OP(6) induced acute anti-hyperalgesic activity in formalin-induced mechanical hyperalgesia but not an anti-inflammatory effect. Repeated administration of OP(5) for 10 days did not induce any anti-hyperalgesic effect. The evaluation of in vivo antioxidant properties showed that OP(5) significantly reduced malondialdehyde and increased superoxide dismutase levels in liver without significantly affecting other oxidative stress and hepatotoxic parameters. Chronic administration of OP(5) did not cause gastric ulceration. CONCLUSION: Cycloartanes isolated from Oxyanthus pallidus possess analgesic effects but lack anti-inflammatory activities. This analgesic effect especially on inflammatory pain may be due to the presence of hydroxyl group in front of the plane. OP(5) is devoid of ulcerogenic effect and possess antioxidant properties that might be of benefit to its analgesic properties.