The mechanisms of the anti-inflammatory activity of the leaf extracts of Culcasia scandens P. Beauv were evaluated. The methanol leaf extract (CE) of C scandens was subjected to bioactivity-guided separation to obtain fraction C as the most active anti-inflammatory fraction. Further activity-guided fractionation of fraction C led to the isolation of an anti-inflammatory principle, CS-1, identified as sitosterol. Phytochemical analysis of CE indicated the presence of carbohydrates, glycosides, alkaloids, saponins, flavonoids, tannins, sterols and terpenoids. Fraction C tested positive for flavonoids, sterols and terpenoids while CS-I tested positive for sterols. Acute toxicity test on CE in mice established an intraperitoneal (i.p.) and oral (p.o.) LD50 of > 5 g/kg. The isolated compound, CS-1, inhibited topical edema in the mouse ear while CE and fraction C were devoid of any such activity. The methanol extract (CE), fraction C and CS-1 suppressed paw edema in rats with inhibitory order of magnitude: CS-1 > fraction C > CE. The methanol extract (CE), fraction C and CS-1 caused gastrointestinal irritation in rats to varying extents and reduced neutrophil and lymphocyte counts while CE and fraction C reduced total leukocyte count (TLC). The methanol extract (CE) was effective in inhibiting heat-induced hemolysis of human red blood cells (RBCs) but exhibited no inhibitory effect on hypotonicity-induced hemolysis. However, fraction C and CS-1 inhibited both heat- and hypotonicity-induced hemolysis. These results suggest that the leaf extract of C scandens has a good anti-inflammatory profile, indicating a nonspecific mechanism of action. (C) 2004 Elsevier Inc. All rights reserved.