ORIGINAL RESEARCH Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.) Soma Ghosh • Debprasad Chattopadhyay • Anurup Mandal • Sudipta Kaity • Amalesh Samanta Received: 14 July 2012 / Accepted: 21 December 2012 / Published online: 8 January 2013 Ó Springer Science+Business Media New York 2013 Abstract 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), vas- cular 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 recor- ded in yeast-induced pyrexia model. Chemical study of CE and ME yielded five known compounds, namely epifriedela- nyl acetate (1), friedelanol (2), b-sitosterol (3), ursolic acid (4), and luteolin (5), along with the new compound 1,2-tetrade- canediol 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 forma- tion 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. Keywords Pedilanthus tithymaloides Á Antiinflammatory Á Carrageenan-induced paw edema Á Antinociceptive Á Antipyretic Introduction India is a rich reservoir of medicinal plants and until recently only a small percentage of these reserves has been scientifically explored. Plant-derived natural products such as flavonoids, terpenes, and alkaloids (Osawa et al., 1990; Keith et al., 1990) have received considerable attention in recent years due to their diverse pharmacological activities, which include antiinflammatory, antipyretic, analgesic. Inflammation is a protective immune response of injured tissues against harmful stimuli whose long-time continua- tion results in a host of diseases, including rheumatoid arthritis, inflammatory bowel disease (Medzhitov, 2008). Although several steroidal and nonsteroidal antiinflamma- tory drugs (NSAID) are available, but most of the current antiinflammatory drugs have toxicity and adverse drug reactions in long-term clinical use. Therefore, the devel- opment of new, less toxic antiinflammatory agents with analgesic potential continues to be of enormous interest. Pedilanthus tithymaloides (L.) Poit. of Euphorbiaceae, commonly known as devil’s-backbone in English, and Brihatgokshura, Trikantaka, or Bhakshantaka in Ayurveda, is a low tropical shrub grown in different parts of India. In Electronic supplementary material The online version of this article (doi:10.1007/s00044-012-0449-4) contains supplementary material, which is available to authorized users. S. Ghosh Á A. Mandal Á S. Kaity Á A. Samanta (&) Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India e-mail: asamanta61@yahoo.co.in D. Chattopadhyay ICMR Virus Unit, I.D and B.G Hospital, Beliaghata, Kolkata 700010, India 123 Med Chem Res (2013) 22:4347–4359 DOI 10.1007/s00044-012-0449-4 MEDICINAL CHEMISTR Y RESEARCH