Biomed Environ Sci, 2014; 27(4): 295-299 295 doi: 10.3967/ bes2014.052 1. Centre of Advanced Study in Marine Biology, Faculty of Marine Sciences, Annamalai University, Parangipettai 608502, Tamil Nadu, India; 2. Nandha College of Pharmacy and Research Institute, Erode, Tamil Nadu, India Letter to the Editor Anti-Nociceptive Effect in Mice of Thillai Flavonoid Rutin Gurudeeban Selvaraj 1,# , Satyavani Kaliamurthi 1 , Ramanathan Thirungnasambandam 1 , Lalitha Vivekanandan 2 , and Balasubramanian Thangavel 1 We investigated the anti-nociceptive effect of Excoecaria agallocha (E.agallocha) against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction (Alk-CF) of E.agallocha by oral administration. Compared with controls, Alk-CF decreased the writhing numbers (P<0.01) in a dose dependent manner. Further we determined that, Alk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.agallocha that involve opioid receptor, and in which the active compound is Rutin. The human environment contains a large number factor responsible for pain which is a sensory modality that often represents the only symptom for the diagnosis of variety diseases. Moreover the administration of synthetic drugs to the treatment of pain is in some cases associated with side effects, such as the induction of gastric lesions by non steroidal anti-inflammatory drugs (NSAIDs) [1] . Plant-based drugs have recently been garnering increased attention and in particular those derived from mangroves, which are used by coastal fishing communities have been both toxicologically and medicinally validated [2] . Mangroves contain a variety of phenolic compounds with biological activity, which includes flavonoids and their glycosylated derivatives performed physiological roles, also act as catalysts and regulators in photo-phosphorylation [3] as well as more than 100 alkaloids. Excoecaria agallocha (E. agallocha) commonly termed as Thillai, is an ever green mangrove of Euphorbiaceae family, which is distributed along the southeast coast of India. Although the extracts of leave and bark of this plant have been used for the treatment of chronic pains, rheumatism, leprosy, paralysis, inflammation and ulcers [4] , it active compound has not yet been identified. Accordingly, the aim of the study was to identify the antinociceptive compounds in the extracts of E. agallocha in animal models and to evaluate its efficiency in in silico docking with cyclooxygenase (COX) receptor. Leaves of E. agallocha were collected from Kollidam coast, Tamil Nadu, India during January 2011. The vouchered specimen (AUCASMB 63/2011) was deposited in the herbarium of C.A.S. in Marine Biology, Annamalai University, Parangipettai, India. 5 kg of air-dried, powdered leaf was extracted with ethanol using a percolation method. The obtained extract was evaporated under reduced pressure to generate a viscous mass. 250 g of extract was suspended in 500 mL of distilled water and partitioned sequentially with n-hexane (5×250 mL), dichloromethane (DCM) (5×250 mL), to generate acid (pH3, 5×250 mL) and alkaline Alk-CF (pH9, 5×250 mL) chloroform fractions. Five fractions were collected and concentrated under vacuum and stored at 20 °C until experiments. Both the total extract and fractions were screened to determine the presence of alkaloids, flavonoids, terpenoids, and saponins [5] . Swiss albino mice of either sex (20-25 g) were used for experiment. The acute oral toxicity study was performed according to OECD-423 guidelines. Animals were fasted for 4 h with free access to water only. Isolated fractions and total extract were suspended in a 0.5% carboxy methyl cellulose (CMC) solution and administered orally at initial doses of 1 to 2000 mg/kg after which mortality was assessed for 3 d [6] . A dose was considered toxic when