沉香精油通过抑制p-STAT3和IL-1β/IL-6产生抗炎作用

Anti-inflammatory Effect of Chinese Agarwood Essential Oil Via Inhibiting p-STAT3 and IL-1β/IL-6

目的沉香是常用名贵药材,因具有多种药效且药用资源稀缺,是目前研究的热点。沉香精油(Chinese eaglewood essential oil,CEEO)是其主要有效成分,本实验旨在研究CEEO的抗炎作用及分子机制。方法采用小鼠耳肿胀实验和大鼠足肿胀实验评价CEEO的抗炎活性;通过脂多糖(LPS)诱导RAW264.7细胞模型研究CEEO对白细胞介素(IL)-1β、IL-6等的影响;采用Western blot方法研究CEEO对大鼠组织蛋白p-STAT3,p-IκBα/p-NF-κBp65的影响;通过气相色谱-质谱联用(GCMS)方法分析CEEO的化学成分。结果CEEO(60~960 mg·kg^-1,ig)剂量依赖地抑制二甲苯所致耳肿胀(P<0.001),最高抑制率为73%;CEEO(680 mg·kg^-1,ig)明显抑制角叉菜胶所致足肿胀(P<0.001),最高抑制率为51%。ELISA和RTPCR结果显示,CEEO(10、5、2.5μg·m L-1)显著抑制IL-1β和IL-6的产生及其mRNA水平(P<0.001),最高抑制率分别为68%和39%,64%和52%。Western blot结果显示,CEEO(680 mg·kg^-1,ig)明显抑制p-STAT3蛋白的表达,抑制率为21%(P<0.05)。通过GC-MS鉴定了沉香中的117个化合物,其主要成分为倍半萜类(68.83%)。结论本实验首次发现中国沉香精油灌胃给药具有显著的抗炎活性,其机制可能是通过降低p-STAT3的过表达,进而抑制前炎症细胞因子IL-1β和IL-6的产生和释放,从而抑制炎症的发生与发展。沉香精油的抗炎作用可能与其所含的主成分倍半萜有关。

OBJECTIVE Eaglewood is a commonly used precious herbal medicine.Due to the multiple drug effects and shortage of medicinal resources,it is currently a hot research topic.Chinese agarwood essential oil(CEEO)is the main active ingredient of eaglewood.To investigate the anti-inflammatory effect and mechanism of CEEO.METHODS The anti-inflammatory effect of CEEO was evaluated on xylene-induced ear edema in mice and carrageenan-induced paw swelling in rats.The production and transcription levels of pro-inflammatory cytokines IL-1βand IL-6 were detected by ELISA or quantitative RT-PCR in LPS-activated RAW264.7 macrophages.The protein levels of p-transducer and activator of transcription 3(STAT3)and p-IκBα/p-NF-κBp65 were detected by Western blot analysis.The chemical profiles of CEEO were identified by GC-MS.RESULTS Intragastric administration with CEEO(60-960 mg·kg-1 in mice and 680 mg·kg^-1 in rats)produced significant anti-inflammatory effect in vivo,the highest inhibition percentages were 73%and 51%,respectively(P<0.001).After treatment with CEEO(10,5,and 2.5μg·mL^-1),ELISA and RT-PCR analysis showed that the production and mRNA level of IL-1βand IL-6 were attenuated by 68%and 39%,64%and 52%(P<0.001),respectively,at the highest concentration.Western blot analysis showed that CEEO(680 mg·kg-1,ig)significantly restrained the phosphorylation of STAT3 by 21%(P<0.05).Totally 117 compounds were identified in CEEO by GC-MS analysis and the chemical analysis revealed that sesquiterpenoids were the major compounds(68.83%).CONCLUSION This study shows for the first time that intragastric administration of CEEO has significant anti-inflammatory effect,which may be due to the suppression of pro-inflammatory cytokines IL-1βand IL-6 by reducing the overexpression of p-STAT3,thereby inhibiting the occurrence and development of inflammation.The anti-inflammatory effect of CEEO may be related to the primary component sesquiterpenoids.