Arch Pharm Res Vol 29, No 8, 617-623, 2006 ~r~ibe~ of !~armaraI ~e~earcb http://apr.psk.or.kr Chemical Constituents of the Root of Dystaenia takeshimana and Their Anti-Inflammatory Activity Ju Sun Kim, Jin Cheul Kim 1, Sang Hee Shim, Eun Ju Lee, WenYi Jin 2, KiHwan Bae 2, Kun Ho Son 3, Hyun Pyo Kim 4, Sam Sik Kang, and Hyeun Wook Chang 1 Natura/ Products Research Institute and College of Pharmacy, Seou/ Nationa/ University, Seou/ 110-460, Korea, 1College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Korea, 2College of Pharmacy, Chungnam National University, Daejeon 305-764, Korea, 3Department of Food and Nutrition, Andong National University, Andong 760-749, Korea, and 4College of Pharmacy, Kangwon National University, Chuncheon 200-701, Korea (Received February 23, 2006) In our ongoing search for bioactive compounds originating from the endemic species in Korea, we found that the hexane and EtOAc fractions of the MeOH extract from the root of Dystaenia takeshimana (Nakai) Kitagawa (Umbelliferae) showed cyclooxygenase-2 (COX-2) and 5- lipoxygenase (5-LOX) dual inhibitory activity by assessing their effects on the production of prostaglandin D2(PGD2) and leukotriene C4 (LTC4) in mouse bone marrow-derived mast cells. By activity-guided fractionation, five coumarins, viz. psoralen (2), xanthotoxin (3), scopoletin (4), umbelliferone (5), and (+)-marmesin (6), together with 13-sitosterol (1), were isolated from the hexane fraction, and two phenethyl alcohol derivatives, viz. 2-methoxy-2-(4'-hydroxyphe- nyl)ethanol (7) and 2-hydroxy-2-(4'-hydroxyphenyl)ethanol (8), three flavonoids, viz. apigenin (9), luteolin (18), and cynaroside (11), as well as daucosterol (12) were isolated from the EtOAc fraction using silica gel column chromatography. In addition, D-mannitol (13) was iso- lated from the BuOH fraction by recrystallization. Two of the coumarins, scopoletin (4) and (+)- marmesin (6), the two phenethyl alcohol derivatives (7, 8) and the three flavonoids (9-11) were isolated for the first time from this plant. Among the compounds isolated from this plant, the five coumarins as well as the three flavonoids showed COX-2/5-LOX dual inhibitory activity. These results suggest that the anti-inflammatory activity of D. takeshimana might in part occur via the inhibition of the generation of eicosanoids. Key words: Dystaenia takeshimana, Umbelliferae, Chemical constituents, Cyclooxygenase-2, 5-Lipoxygenase, Anti-inflammatory activity INTRODUCTION Dystaenia takeshimana (Nakai) Kitagawa, which belongs to the family Umbelliferae, is a 1.5-2 meter tall perennial herb distributed in Ulreung island as an endemic species in Korea. The root of this plant has long been used as pig feed and is sometimes called pig herb (Lee, 1996). Previous phytochemical investigations carried out on the roots of this plant resulted in the isolation of various coumarins and sterols, as well as mannitol (Kwon et al., Correspondence to: Hyeun Wook Chang, College of Pharmacy, Yeungnam University,Gyeongsan 712-749, Korea Tel: 82-53-810-2811, Fax: 82-53-810-4654 E-mail: hwchang@yu.ac.kr Sam Sik Kang, Natural Products Research Institute and College of Pharmacy, Seoul National University, Seoul 110-460, Korea Tel: 82-2-740-8925, Fax: 82-2-743-3323 E-mail: sskang@snu.ac.kr 1992; Kim et al., 1993). A preliminary biological assay on D. takeshimana indicated that the MeOH extracts of the roots and herbs exhibited potent inhibitory activity against NO production in LPS-activated murine macrophage-like RAW 264.7 cells (Kim et al., 2004). During the course of our studies on the bioactive constituents derived from the endemic species in Korea (Park et aL, 2002; Jung et al., 2002; Thuong et al., 2005), we found that the hexane and EtOAc fractions of the MeOH extract showed potent inhibitory effects in the COX-2 and 5-LOX assays. However, the bioactive constituents of the roots of D. takeshimana have not yet been characterized. This paper describes the isolation, identification and biological activity of the compounds from the bioactive fractions, along with the inhibitory effects of the isolates on COX-2 and 5-LOX. Therefore, the development of dual inhibitors, which can simultaneously inhibit CQX-2/5-LOX, might enhance their 617