Quantification of Major Compounds from Ixeris dentata, Ixeris dentata Var. albiflora, and Ixeris sonchifolia and Their Comparative Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW 264.7 Cells

다국어 초록 (Multilingual Abstract)

The aim of the present study was to evaluate the comparative anti-inflammatory activities of Ixeris dentata (ID), Ixeris dentata var. albiflora (IDA), and Ixeris sonchifolia (IS) and to identify the main compounds present in extracts. The anti-inflammatory activity was evaluated through lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 murine macrophages. Five main compounds consisting of chlorogenic acid, caffeic acid, luteolin 7-O-glucoside, luteolin 7-O-glucuronide, and luteolin were used for simultaneous high-performance liquid chromatography quantification. The total phenolic content present in ID (30 mg/g GAE), IDA (35.33 mg/g GAE), and IS (43.79 mg/g GAE) was correlated to the corresponding LPS-induced NO production inhibitory effect in RAW 264.7 cells as expressed with IC50 values 26.19, 21.43, and 7.59 μg/mL, respectively. Luteolin 7-O-glucoside was found as the major compound in ID (8.76 mg/g dry weight) and IDA (10.35 mg/g dry weight) and luteolin 7-O-glucuronide was the major compound in IS (34.66 mg/g dry weight). Luteolin 7-O-glucoside and luteolin 7-O-glucuronide inhibited LPS-induced NO production with IC50 values of 30 and 4.5 μM, respectively. Furthermore, luteolin, luteolin 7-O-glucoside, and luteolin 7-O-glucuronide suppressed the expression of iNOS and COX-2, and t-BHP-induced ROS generation in LPS-stimulated RAW 264.7 cells. These results clearly showed that the anti-inflammatory potential of ID, IDA, and IS extract are primarily due to their contents of luteolin 7-O-glucoside and luteolin 7-O-glucuronide, respectively.

참고문헌 (Reference)

• 1 홍슬기, "흰씀바귀 (苦菜, Ixeris dentata var. albiflora Nakai)뿌리의 성분 분석과 추출물의 세포 생존율 및 DPPH 라디칼 소거 활성" 한국영양학회 43 (43): 105-113, 2010
• 2 이은, "씀바귀 추출물이 LPS투여 흰쥐 및 Raw 264.7세포에서 전염증성 cytokines 생성에 미치는 영향" 한국자원식물학회 24 (24): 604-612, 2011
• 3 Sharif O, "Transcriptional profiling of the LPS induced NF-jB response in macrophages" 8 : 1-17, 2007
• 4 Park KH, "The anti-oxidative and antiinflammatory effects of caffeoyl derivatives from the roots of Aconitum koreanum R" 32 : 2029-2033, 2009
• 5 Shi P, "Systematic characterisation of secondary metabolites from Ixeris sonchifolia by the combined use of HPLC-TOFMS and HPLC-ITMS" 22 : 66-73, 2011
• 6 Zhang YC, "Studies on the chemical constituents and biological activities of Ixeris" 10 : 1373-1391, 2013
• 7 Ye G, "Structure elucidation and complete NMR spectral assignments of a novel sesquiterpene glycoside from Ixeris sonchifolia" 45 : 362-363, 2007
• 8 Sun Q, "Simultaneous analysis of 11 main active components in Cirsium setosum based on HPLC-ESI-MS/MS and combinedwith statistical methods" 35 : 2897-2907, 2012
• 9 Seto M, "Sesquiterpene lactones from Ixeris dentata Nakai" 34 : 4170-4176, 1986
• 10 Lebel CP, "Sensitive and rapid quantitation of oxygen reactive species formation in rat synaptosomes" 17 : 435-440, 1990
• 11 Mossman T, "Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays" 65 : 55-63, 1983
• 12 Kong LY, "RP-HPLC determination of adenosine in herb of Ixeris sonchifolia (Bge.) Hance" 26 : 1665-1667, 2006
• 13 Heiss E, "Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms" 276 : 32008-32015, 2001
• 14 Chung HS, "Nitric oxide and tumor necrosis factor-a production by Ixeris dentata in mouse peritoneal macrophages" 82 : 217-222, 2002
• 15 Kwon SH, "Neuroprotective effects of chlorogenic acid on scopolamine-induced amnesia via antiacetylcholinesterase and anti-oxidative activities in mice" 649 : 210-217, 2010
• 16 박충무, "Luteolin and luteolin-7-O-glucoside inhibit lipopolysaccharide-induced inflammatory responses through modulation of NF-κB/AP-1/PI3K-Akt signaling cascades in RAW 264.7 cells" 한국영양학회 7 (7): 423-429, 2013
• 17 Hu C, "Luteolin and luteolin-7-O-glucoside from dandelion flower suppress iNOS and COX-2 in RAW 264.7 cells" 265 : 107-113, 2004
• 18 Park, Eun-Kyung, "Lactic Acid Bacterial Fermentation Increases the Antiallergic Effects ofIxeris dentata" 한국미생물·생명공학회 18 (18): 308-313, 2008
• 19 Lee HY, "Ixeris dentata induced regulation of amylase synthesis and secretion in glucose-treated human salivary gland cells" 62 : 739-749, 2013
• 20 Kim DS, "Ixeris dentata Nakai reduces clinical score and HIF-1expression in experimental colitis in mice" 2013 : 671281-, 2013
• 21 Nishitani Y, "Intestinal antiinflammatory activity of luteolin: role of the aglycone in NFkappaB inactivation in macrophages co-cultured with intestinal epithelial cells" 39 : 522-533, 2013
• 22 Ju HK, "Inhibitory effects of nardostachin on nitric oxide, prostaglandin E2, and tumor necrosis factor-a production in lipopolysaccharide activated macrophages" 26 : 1375-1378, 2003
• 23 Quillet-Mary A, "Implication of mitochondrial hydrogen peroxide generation in ceramide-induced apoptosis" 272 : 21388-21395, 1997
• 24 Choi JS, "Hyperglycemic and hyperlipemic effects of Ixeris dentata in diabetic rats" 13 : 269-273, 1990
• 25 Husain SR, "Hydroxyl radical scavenging activity of flavonoids" 26 : 2489-2491, 1989
• 26 Nugroho A, "Highperformance liquid chromatographic quantification and validation of luteolin glycosides from Sonchus brachyotus and their peroxynitrite-scavenging activity" 18 : 39-46, 2012
• 27 Zhong Y, "Great Dictionary of Chinese Medicinals. Vol. 1" Shanghai Science and Technological Publisher 589-597, 1985
• 28 Valko M, "Free radicals and antioxidants in normal physiological functions and human disease" 39 : 44-84, 2007
• 29 Garcia-Lafuente A, "Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease" 58 : 537-552, 2009
• 30 Heim KE, "Flavonoid antioxidants:chemistry, metabolism and structure-activity relationships" 13 : 572-584, 2002
• 31 Ainsworth EA, "Estimation of total phenolic content and other oxidation substrates in plant tissues using Folin-Ciocalteu reagent" 2 : 875-877, 2007
• 32 Petros A, "Effect of nitric oxide synthase inhibitors on hypotension in patients with septic shock" 338 : 1557-1558, 1991
• 33 Yin R, "Determination of five components in Ixeris sonchifolia by high performance liquid chromatography" 43 : 1364-1369, 2007
• 34 안은미, "Cytotoxic and ACAT-inhibitory Sesquiterpene Lactones from the Root of Ixeris dentata forma albiflora" 대한약학회 29 (29): 937-941, 2006
• 35 Wang LZ, "Clinical observation on the effect of Ixeris Sonchifolia Hance injection on the treatment of 40 angina pectoris of coronary heart disease phlegm obstruction patients" 29 : 6-8, 2008
• 36 Huang HM, "Clinical efficiency evaluation of Kudiezi injection on treating 65 cerebral infarction patients" 15 : 389-, 2008
• 37 Ferrero-Miliani L, "Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta generation" 147 : 227-235, 2007
• 38 Shan J, "Chlorogenic acid inhibits lipopolysaccharide-induced cyclooxygenase-2 expression in RAW 264.7 cells through suppressing NF-jB and JNK/AP-1 activation" 9 : 1042-1048, 2009
• 39 Brock TG, "Arachidonic acid is preferentially metabolized by cyclooxygenase-2 to prostacyclin and prostaglandin E2" 274 : 11660-11666, 1991
• 40 Rice-Evans CA, "Antioxidant properties of phenolic compounds" 2 : 152-159, 1997
• 41 Huang SS, "Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima" 147 : 395-405, 2013
• 42 Shin EM, "Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis in LPS-stimulated RAW 264.7 macrophages" 8 : 1524-1532, 2008
• 43 Jung HA, "Anti-inflammatory activity of Korean thistle Cirsium maackii and its major flavonoid, luteolin 5-O-glucoside" 50 : 2171-2179, 2012
• 44 Francisco V, "Anti-inflammatory activity of Cymbopogon citratus leaves infusion via proteasome and nuclear factor-kappaB pathway inhibition: contribution of chlorogenic acid" 148 : 126-134, 2013