Flavonoid glycosides from the leaves of Allium victorialis var. platyphyllum and their anti-neuroinflammatory effects Kyeong Wan Woo a , Eunjung Moon b , So Young Park c , Sun Yeou Kim d , Kang Ro Lee a,⇑ a Natural Products Laboratory, School of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon, Gyeonggi-do 440-746, Republic of Korea b Graduate School of East-West Medical Science, Kyung Hee University Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea c Laboratory of Pharmacognosy, College of Pharmacy, Dankook University, San#29, Anseo-dong, Dongnam-gu, Cheonan 330-714, Republic of Korea d College of Pharmacy, Gachon University, #191 Hambakmoe-ro, Yeonsu-gu, Incheon 406-799, Republic of Korea article info Article history: Received 3 September 2012 Revised 4 October 2012 Accepted 9 October 2012 Available online 23 October 2012 Keywords: Allium victorialis var. platyphyllum Liliaceae Allivictoside A–H Anti-neuroinflammatory effect abstract Eight new flavonoid glycosides, named allivictoside A–H (1–8), together with twelve known flavonoids (9–20) were isolated from the leaves of Allium victorialis var. platyphyllum. The structures of 1–8 were determined by chemical and spectroscopic methods, including 1D, 2D NMR analyses and HR-MS. To eval- uate the anti-neuroinflammatory activities of all isolates, we measured the secreted nitric oxide levels in murine microglia BV-2 cells stimulated by lipopolysaccharide. In this study, compounds 2, 6, 10, and 18 significantly inhibited nitric oxide production (IC 50 values of 20.67, 20.42, 21.48 and 19.80 lM, respectively) without cell toxicity. Therefore, we suggest that allivictoside B (2) and F (6), 3-O-b-D-gluco- syl-7-O-b-D-(2-O-feruloyl)glucosylkaempferol (10) and quercetin 3-O-b-D-glucopyranoside (18) may be considered as candidates for the treatment of diseases associated with neuroinflammation. Ó 2012 Elsevier Ltd. All rights reserved. Neuroinflammation is a general innate immune response of the brain aimed at protecting the central nervous system (CNS) against infectious pathogens and injuries. 1 In most cases, it plays impor- tant roles in the defense against injury and restoring homeostasis. However, chronic neuroinflammation may contribute to the pro- gressive neuronal damage observed in many neurodegenerative disorders, most notably parkinson’s disease, alzheimer’s disease and neuronal injury associated with stroke. 2–4 Therefore, the role of neuroinflammation has become a prominent theme for investi- gation in various neurological diseases and neuroprotective drug development. Microglia are the immune cells present in the CNS. However, uncontrolled and chronic activated microglia contribute to produce various proinflammatory factors such as nitric oxide (NO), tumor necrosis factor a (TNF-a), and prostaglandin E 2 (PGE 2 ). These factors become important causes of inflammation in the brain, and finally contribute to neuroinflammation. 5 Thus, many studies have been focusing on the development of materials that can inhibit microglia activation in a safer and more effective fashion. The genus Allium contains about 20 species. Among the species, Allium victorialis var. platyphyllum (Liliaceae), better known as ‘Myung-i’ in Korea, is widely distributed in the northern part of Korea. The leaves of A. victorialis var. platyphyllum are used as veg- etable, such as pickles in soy sauce, wrapped pock, and kim-chi and also as a Korean traditional medicine for the treatment of gastritis and heart failures. 6 It has been reported that the EtOH extract of A. victorialis var. platyphyllum showed several pharmacological activ- ities including anti-hyperlipidemic, anti-obesity, 7 anti-athero- genic, 8 cytotoxic, 9 and anti-hepatotoxic effects. 10 Previous phytochemical studies on this plant reported the isolation of flavo- noids, steroidal saponins, and sulfur compounds. 11–13 However, the effects of flavonoids isolated from A. victorialis var. platyphyllum on the regulation of neuroinflammation have not yet been reported. Herein, we describe the structural elucidation of new isolated flavonoid glycosides (1–8), named allivictoside A–H (1–8) (Figure 1), on the basis of 1D, 2D NMR data and chemical methods, and evaluation of the anti-neuroinflammatory activities of all iso- lated compounds by measuring the production of proinflammatory factor and nitric oxide (NO) in lipopolysaccharide (LPS)-activated murine microglia BV-2 cells. The half dried leaves of A. victorialis var. platyphyllum (2.7 kg) were extracted with 80% MeOH three times at room temperature and evaporated under reduced pressure to give a residue (314.0 g), which was dissolved in water (800 ml) and partitioned with solvent to give n-hexane (17.0 g), CHCl 3 (2.2 g), EtOAc (3.4 g) and n-BuOH (50.0 g) soluble portions. Purification of the EtOAc and n-BuOH-soluble fractions by multiple chromatographic steps (Supplementary data) led to the isolation of eight new flavonoid gly- cosides, together with twelve known flavonoid derivatives. The isolated known compounds were identified as kaempferol 7-O-b- D-glucopyranoside (9), 3-O-b-D-glucosyl-7-O-b-D-(2-O-feruloyl)glu- cosylkaempferol (10), kaempferol 3,7,4 0 -tri-O-b-D-glucopyranoside 0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bmcl.2012.10.043 ⇑ Corresponding author. Tel.: +82 31 290 7710; fax: +82 31 290 7730. E-mail address: krlee@skku.ac.kr (K.R. Lee). Bioorganic & Medicinal Chemistry Letters 22 (2012) 7465–7470 Contents lists available at SciVerse ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl