Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)

Pedilanthus tithymaloides (PT) leaves are widely used in Indian medicine to treat inflammation and pain, but until recently no systematic study of these activities were reported. This study aimed to evaluate the antiinflammatory, antinociceptive, and antipyretic activity of the chloroform (CE) and methanol extract (ME) of PT leaves and its isolated constituents in animal models. The results revealed significant antiinflammatory activity of CE and ME in carrageenan-induced paw edema (acute), vascular permeability and cotton pellet granuloma (chronic) models. Both extracts also produced significant increase in hot-plate reaction time but decrease in writhing response in a dose-dependent manner, indicating their antinociceptive activity. Moreover, significant antipyretic activity was recorded in yeast-induced pyrexia model. Chemical study of CE and ME yielded five known compounds, namely epifriedelanyl acetate (1), friedelanol (2), β-sitosterol (3), ursolic acid (4), and luteolin (5), along with the new compound 1,2-tetradecanediol 1-(hydrogen sulfate) sodium salt (6). This is the first report showing isolation of compound 5 from PT leaves, and of compound 6, from any plant source. Among these, compounds 4 and 5 (10 mg/kg, p.o.) produced significant inhibition of pain response elicited by acetic acid, increased latency in hot-plate, and caused inhibition of carrageenan-induced edema and cotton pellet-induced granuloma formation in mice. Thus, our results clearly demonstrated the justification of the traditional use of P. tithymaloides leaves as an antiinflammatory drug in primary health care.