Lin Guochao, Gao Shuang, Cheng Jinli, Li Yinghua, Shan Lei, Hu Zhenlin
a School of Pharmacy, the Second Military Medical University , Shanghai , China.
Pharm Biol. 2016;54(3):516-22. doi: 10.3109/13880209.2015.1050745. Epub 2015 May 28.
1β-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions.
The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB).
AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 μL of 5% DNCB on their shaved back skin and then challenging with 20 μL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge.
IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFα, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFα, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 μM, respectively, and inhibited the activation of NF-κB pathway in TNFα-stimulated HaCat cells.
The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.
1β-羟基土木香内酯(IJ-5)是从旋覆花(菊科)中分离得到的一种倍半萜内酯化合物。倍半萜内酯已被证明可调节许多影响炎症反应的过程。
本研究在2,4-二硝基氯苯(DNCB)诱导的小鼠特应性皮炎(AD)模型中研究IJ-5的保护作用。
通过在Balb/c小鼠剃毛的背部皮肤涂抹100μL 5% DNCB致敏一次,然后在致敏后第5天开始,每隔3天用20μL 0.2% DNCB对其右耳进行5次激发,诱导出类似AD的皮肤损伤。在每次DNCB激发前1小时,以10mg/kg的剂量腹腔注射IJ-5。
IJ-5治疗减轻了DNCB诱导的皮炎严重程度和右耳肿胀。IJ-5治疗组小鼠血清中IgE、IL-4和IL-6水平分别降低了54.7%、56.5%和53.0%,而IJ-5治疗组小鼠背部皮肤损伤中TNFα、IL-1、IL-4和IL-6的mRNA水平与未治疗的对照组相比分别降低了47.7%、61.5%、57.5%和58.5%。组织病理学检查显示,IJ-5治疗减少了DNCB诱导的耳部和背部皮肤的肥大、角化过度和炎性细胞浸润。此外,IJ-5抑制TNFα、IL-1和IL-6的表达,IC50值分别为6.58、9.48和7.01μM,并在TNFα刺激的HaCat细胞中抑制NF-κB通路的激活。
本研究证明了IJ-5对类似AD的皮肤炎症具有保护作用,并突出了IJ-5作为AD潜在治疗药物的地位。