Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice

Chung-Mu Park,Young-Sun Song 한국영양학회 2019 Nutrition Research and Practice Vol.13 No.6

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and 10 μg/kg BW, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and TNF-α levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

Luteolin and luteolin-7-O-glucoside protect against acute liver injury through regulation of inflammatory mediators and antioxidative enzymes in GalN/LPS-induced hepatitic ICR mice

Park, Chung Mu,Song, Young-Sun The Korean Nutrition Society 2019 Nutrition Research and Practice Vol.13 No.6

BACKGROUND/OBJECTIVES: Anti-inflammatory and antioxidative activities of luteolin and luteolin-7-O-glucoside were compared in galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatitic ICR mice. MATERIALS/METHODS: Male ICR mice (6 weeks old) were divided into 4 groups: normal control, GalN/LPS, luteolin, and luteolin-7-O-glucoside groups. The latter two groups were administered luteolin or luteolin-7-O-glucoside (50 mg/kg BW) daily by gavage for 3 weeks after which hepatitis was induced by intraperitoneal injection of GalN and LPS (1 g/kg BW and $10{\mu}g/kg\;BW$, respectively). RESULTS: GalN/LPS produced acute hepatic injury by a sharp increase in serum AST, ALT, and $TNF-{\alpha}$ levels, increases that were ameliorated in the experimental groups. In addition, markedly increased expressions of cyclooxygenase (COX)-2 and its transcription factors, nuclear factor $(NF)-{\kappa}B$ and activator protein (AP)-1, were also significantly attenuated in the experimental groups. Compared to luteolin-7-O-glucoside, luteolin more potently ameliorated the levels of inflammatory mediators. Phase II enzymes levels and NF-E2 p45-related factor (Nrf)-2 activation that were decreased by GalN/LPS were increased by luteolin and luteolin-7-O-glucoside administration. In addition, compared to luteolin, luteolin-7-O-glucoside acted as a more potent inducer of changes in phase II enzymes. Liver histopathology results were consistent with the mediator and enzyme results. CONCLUSION: Luteolin and luteolin-7-O-glucoside protect against GalN/LPS-induced hepatotoxicity through the regulation of inflammatory mediators and phase II enzymes.

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

Subash Karki,박희준,Agung Nugroho,김언지,정현아,최재수 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.1

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.

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

Chung Mu Park,Young-Sun Song 한국영양학회 2013 Nutrition Research and Practice Vol.7 No.6

Luteolin is a flavonoid found in abundance in celery, green pepper, and dandelions. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-inflammatory capacity of luteolin and one of its glycosidic forms, luteolin-7-O-glucoside, were compared and their molecular mechanisms of action were analyzed. In lipopolysaccharide (LPS)-activated RAW 264.7 cells, luteolin more potently inhibited the production of nitric oxide (NO) and prostaglandin E2 as well as the expression of their corresponding enzymes (inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) than luteolin-7-O-glucoside. The molecular mechanisms underlying these effects were investigated to determine whether the inflammatory response was related to the transcription factors, nuclear factor (NF)-κB and activator protein (AP)-1, or their upstream signaling molecules, mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K). Luteolin attenuated the activation of both transcription factors, NF-κB and AP-1, while luteolin-7-O-glucoside only impeded NF-κB activation. However, both flavonoids inhibited Akt phosphorylation in a dose-dependent manner. Consequently, luteolin more potently ameliorated LPS-induced inflammation than luteolin-7-O-glucoside, which might be attributed to the differentially activated NF-κB/AP-1/PI3K-Akt pathway in RAW 264.7 cells.

Luteolin-7-O-glucoside가 멜라닌 합성에 미치는 영향

최병민,홍혜현,박태진,김승영 한국응용생명화학회 2022 Journal of Applied Biological Chemistry (J. Appl. Vol.65 No.3

Biorenovation은 미생물의 효소 작용을 통해 기존의 화합물을새로운 화합물로 전환시키는 방법이다. 본 연구에서는biorenovation을 Luteolin에 적용하여 Luteolin-7-O-glucoside (L7G)를 합성하였으며 L7G의 미백 기능성을 평가하고자 α- MSH로 유도된 B16F10 mouse melanoma 세포에서 실험을 진행하였다. L7G는 Luteolin의 높은 세포독성을 개선하였으며 세포 독성이 나타나지 않는 농도에서 melanin 합성 및 tyrosinase 생성을 유의하게 억제하였다. 또한 western blot을 통해 멜라닌의 합성 인자들의 발현을 조사한 결과 tyrosinase와 MITF의 발현이 효과적으로 억제되는 것을 확인하였다. 결론적으로 우리는L7G가 멜라닌의 합성을 억제함으로써 피부 미백에 긍정적인 영향을 나타낼 수 있음을 확인하였으며 이러한 결과를 근거로L7G가 미백 기능성 원료로써 활용 가능함을 제안한다.

Biological activity of flavonoids from Sonchus brachyotus

Jeong Min Lee,Mi-Jin Yim,김현수,고석천,Ji-Yul Kim,Jung Min Shin,이대성 한국수산과학회 2021 Fisheries and Aquatic Sciences Vol.24 No.12

The aim of this study was to isolate and identify secondary metabolites from Sonchus brachyotus and evaluate their antioxidant and anti-inflammatory activities. In this study, we isolated three flavonoids from a 70% EtOH extract by Medium Pressure Liquid Chromatography (MPLC) and prep-High-Performance Liquid Chromatography (HPLC). To evaluate the biological activities (antioxidant and anti-inflammatory) of these flavonoids, their in vitro inhibitory activities against lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation, nitric oxide (NO) production, and prostaglandin E2 (PGE2) secretion were determined. We successfully identified three flavonoids, namely luteolin (1), luteolin-7-O-β-D-glucoside (2), and luteolin-7-O-β-D-glucuronide (3) by spectral analyses. Luteolin (1) at 20 μg/mL inhibited ROS generation, NO production, and PGE2 secretion by 48.6%, 61.28% and 12.10%, respectively, and luteolin-7-O-β-D-glucoside (2) inhibited NO and PGE2 generation by 67.03% and 20.82%, respectively. Luteolin (1) and luteolin-7-O-β-D-glucoside (2) showed similar anti-inflammatory activities; however, luteolin (1) was observed to be a stronger antioxidant. Besides antioxidant and anti-inflammatory activities, S. brachyotus extract containing luteolin (1) and luteolin- 7-O-β-D-glucoside (2) is considered to possess diverse biological activities. The results indicate that S. brachyotus is an edible medicinal plant, which is believed to be significant resource of functional foods.

톱풀의 항산화 성분

문형인,류승효,노종화,지옥표 한국약용작물학회 2000 한국약용작물학회지 Vol.8 No.1

톱풀 Achillea sibirica Ledeb. (Compositae: 국화과)은 국내 산지의 초원에 널리 분포하는 흰색꽃이 피는 다년생 초본으로 민간에서 봄의 어린 순을 나물로 먹고 전초와 종자를 말린 것(신초;神草) 을 , 건위(健胃), 강장(彈壯), 해열(解熱), 진경(鎭湮), 진통(鎭痛), 정기증진 (精氣增進), 출혈이 심한 치질에 사용해 왔다. 천연물로부터의 우수한 항산화제의 개발의 일환으로 이 식물의 전초의 MeOH extract와 그것의 Hexane fraction., Methyene Chloride fraction., Ethyl Acetate fraction, Butanol fration 에 대해 DPPH radical 소거 효과에 의한 검색을 실시한 결과 EtOAc 분획에서 우수한 항산화 활성을 나타내어 그 EtOAc 용매분획층을 column chromatography 하여 2종의 flavonoid glycoside (E-1,2) 를 분리하였으며, hexane분획에서의 1종의 sterol 화합물 (H-1)과 더불어 각종 이화학적 성상과 spectral data로부터 구조를 동정한 결과 각각 sterol mixture (H-1), kaempferol-3-O-glucoside(E-1), luteolin-7-O- neohesperidoside(E-2)로 확정하였고, 그 중 화합 H-1은 campesterol, stigmasterol, β-sitosterol이 혼합되어 있음을 확인하였다. 화합물 E-1, 2에 대해 항산화 활성 검색을 실시하여, DPPH radical 소거 효과에 의한 검색에서 각각 12.5μg/ml과 15.4μg/ml에서 EC50을 나타내어 항산화 효과를 보였고, TBA에 의한 비색정량법에 의한 항산화 활성 검색에도 항산화 효과를 보였다. Achillea sibirica Ledeb. is widely distributed in Korea and has been often used as folk medicine in peptic and tonic. As one of our searches for bioactive (anti oxidation) compounds from medicinal plants, we studied Achillea sibirica Ledeb. (Compositae). Antioxidant activity of Achillea sibirica was determined by measuring lipid peroxide produced when a mouse liver homogenate was exposed at 90℃ using 2-thiobarbituric acid (TBA) and by evaluation the radical scavenging activity on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical. Whole parts of Achillea sibirica was extracted with methanol and its extracts was fractionated with organic solvent; n-Hexane, methylene chloride, ethyl acetate, n-Butanol. EtOAc fraction exhibited antioxidant activity and From its, two flavonoid glycosides were isolated by silica gel and gel filtration colume chromatography and identified to kampferol 3-O-glucoside and luteolin 7-O-neo-hesperidoside, respectively, by physico-chemical and spectroscopical method. At antioxidant activity test for two compounds isolated, antioxidant activity was showed too. And from hexane fraction sterol was is isolated and identificated to mixture of campesterol, stigmasterol, and β-sitosterol.

환삼덩굴로부터 분리한 Luteolin-7-O-$\beta$-D-Glucoside의 활성산소 소거능

정신교,박승우,박종철 한국식품영양과학회 2000 한국식품영양과학회지 Vol.29 No.1

We investigated the active oxygen scavenging activity and active compound from Humulus japonicus. The ethyl acetate and butanol fraction exhibited strong scavenging effects on hydroxyl radical. Furthermore active compound was isolated and purified using Amberlite XAD-2 column chromatography and preparative HPLC from ethyl acetate fracton, and major compound was identified as a luteolin-7-O-$\beta$-D-glucoside by the MS, UV, 1H-NMR and 13C-NMR analyses. Luteolin-7-O-$\beta$-D-glucoside exhibited strong scavenging effect on active oxygens such as superoxide radical, hydroxyl radical and hydrogen peroxide.

Angelica keiskei의 고지혈증 개선효과 및 2종의 플라본 7-O-배당체의 분리

박종철,조영숙,박석규,박정로,전순실,옥광대,최종원,Park, Jong-Cheol,Cho, Young-Sook,Park, Seok-Kyu,Park, Jeong-Ro,Chun, Soon-Sil,Ok, Kwang-Dae,Choi, Jong-Won 한국생약학회 1995 생약학회지 Vol.26 No.4

Two flavone glycosides were isolated from the aerial part of Angelica keiskei Koidz and identified by means of spectral analysis as luteolin-$7-O-{\beta}-{_D}-glucoside$ and Iuteolin-7-O-rutinoside. Intraperitoneal administration of methanolic extract(100mg/kg) and $luteolin-7-O-{\beta}-{_D}-glucoside(5mg/kg)$ isolated from this plant produced a significant hypolipemic activity.

가죽나무 에타놀 추출물 및 luteolin-7-O-glucoside의phospholipase A2 저해활성

장현욱,김미화,황남경,홍태균,김윤경,정환기,양주혜,전철구,배기환,Pham Ngoc Thanh,손건호,김현표,강삼식 한국생약학회 2007 생약학회지 Vol.38 No.3

our continuing effort to investigate compounds having anti-inflammatory activity from natural products, Ail-anthus altissima was examined. Among six compounds isolated from Ailanthus altissima, Luteolin-7-O-glucoside (L7G) alongwith ethanol extract of Ailnathus altissima (EAa) were chosen to determine their inhibitory activity on secretory recombinantphospholipase A2s enzyme activity in vitro 2-V (IC50 of about 100g/ml) and cPLA2, (IC50 of about 59g/ml), while L7G showed strong inhibitory effect on sPLA2-A, V and cPLA2 with an IC50value of approximately 40M, respectively.Key wordsAilanthus altissima, Luteolin-7-O-glucoside, Phospholipase A2, inflamation... ... .... phospholipase A2(PLA2). ..... ...... arachidonic acid(AA) . lysophos-pholipid. .... . PLA2. .. ... AA. cyclooxy-genase(COX). lipoxygenase(LOX). .. ... ....... prostaglandins(PGs), thromboxanes(TXs) .leukotrienes(LTs). .. .... . .. ... lysophos-pholipid. .. .... .... ..... ... ...... .... platelet activating factor(PAF, ........ ). ..... PLA2. ... ...... .