Cycloartanes from Oxyanthus pallidus and derivatives with analgesic activities

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.

Three cycloartanes OP3, OP5 and OP6 obtained by successive chromatography of the crude methanol extract of the leaves were hydrolysed to yield respective aglycone AOP1, AOP2, AOP3 and acetylated to HOP1, HOP2 and HOP3 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 OP5 were evaluated at the doses of 2.5 and 5 mg/kg/day administered orally. OP6 was also evaluated in acute experiments. The antioxidant and hepato-protective activities of OP5 were evaluated at the end of the chronic treatment.

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. OP5 and OP6 induced acute anti-hyperalgesic activity in formalin-induced mechanical hyperalgesia but not an anti-inflammatory effect. Repeated administration of OP5 for 10 days did not induce any anti-hyperalgesic effect. The evaluation of in vivo antioxidant properties showed that OP5 significantly reduced malondialdehyde and increased superoxide dismutase levels in liver without significantly affecting other oxidative stress and hepatotoxic parameters. Chronic administration of OP5 did not cause gastric ulceration.

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. OP5 is devoid of ulcerogenic effect and possess antioxidant properties that might be of benefit to its analgesic properties.