Yang In Jun, Lee Dong Ung, Shin Heung Mook
Department of Physiology, College of Korean Medicine .
Immunopharmacol Immunotoxicol. 2015 Jun;37(3):308-17. doi: 10.3109/08923973.2015.1038751. Epub 2015 May 20.
Foeniculum vulgare (F. vulgare) is traditionally used to treat inflammatory diseases. Recently, anti-inflammatory and antioxidant activities of methanol extract of the fruits of F. vulgare were reported. To identify biologically active compounds responsible for the anti-inflammatory activity, we isolated four coumarins, scopoletin, 8-methoxypsoralen, bergapten and imperatorin from the fruits of F. vulgare.
This study assessed the anti-inflammatory and antioxidant effects of coumarins isolated from F. vulgare in lipopolysaccharide (LPS)-stimulated macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice.
RAW 264.7 cells were treated with the coumarins (30 µM) and then stimulated with LPS (100 ng/ml). Ears of ICR mice were treated with TPA (1 µg/ear) once a day. Ten microliters each of the four coumarins (200 μg/ml) were topically applied to the ears for 3 days. Antioxidant activities were examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethylbenzthiazoline-6-sulfonic acid (ABTS) scavenging assays.
All the tested coumarins showed excellent antioxidant activities in DPPH and ABTS radical scavenging assays. Among the coumarins, imperatorin had the greatest anti-inflammatory activities as measured by inhibition of the pro-inflammatory cytokines production including interleukin (IL)-6 and tumor necrosis factor (TNF)-α in LPS-stimulated RAW 264.7 cells through blockade of the IκB kinase (IKK)/inhibitor of kappa B (IκB)/nuclear factor-κB (NF-κB) pathway. In vivo experiments showed that imperatorin reduced TPA-induced ear thickness/weight, cutaneous cytokines expression and improved histopathological features.
Although four coumarins isolated from the fruits of F. vulgare provide effective anti-inflammatory and antioxidant activities, imperatorin is most potent.
小茴香传统上用于治疗炎症性疾病。最近，有报道称小茴香果实甲醇提取物具有抗炎和抗氧化活性。为了鉴定具有抗炎活性的生物活性化合物，我们从小茴香果实中分离出了四种香豆素，即东莨菪素、8-甲氧基补骨脂素、佛手柑内酯和欧前胡素。
本研究评估了从小茴香中分离出的香豆素对脂多糖（LPS）刺激的巨噬细胞和12-O-十四酰佛波醇-13-乙酸酯（TPA）刺激的小鼠的抗炎和抗氧化作用。
用香豆素（30μM）处理RAW 264.7细胞，然后用LPS（100 ng/ml）刺激。每天用TPA（1μg/耳）处理ICR小鼠的耳朵一次。将四种香豆素（200μg/ml）各10微升局部涂抹在耳朵上，持续3天。使用2,2-二苯基-1-苦基肼（DPPH）和2,2'-偶氮二（3-乙基苯并噻唑啉-6-磺酸）（ABTS）清除试验检测抗氧化活性。
在DPPH和ABTS自由基清除试验中，所有测试的香豆素均表现出优异的抗氧化活性。在香豆素中，通过阻断IκB激酶（IKK）/κB抑制蛋白（IκB）/核因子κB（NF-κB）途径，欧前胡素在抑制LPS刺激的RAW 264.7细胞中促炎细胞因子（包括白细胞介素（IL）-6和肿瘤坏死因子（TNF）-α）产生方面具有最大的抗炎活性。体内实验表明，欧前胡素可降低TPA诱导的耳厚度/重量、皮肤细胞因子表达并改善组织病理学特征。
虽然从小茴香果实中分离出的四种香豆素均具有有效的抗炎和抗氧化活性，但欧前胡素的活性最强。
