The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse
The most bioactive fraction of stir-fried Radix Paeoniae Alba regulating IL-6/STAT3 signaling pathway in allergic asthma mouse
复制标题
炒白芍最具生物活性部位调节过敏性哮喘小鼠IL-6/STAT3信号通路
DOI：
10.1016/j.jep.2022.115821
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发表时间：
2023
影响因子：
5.4
通讯作者：
Gang Cao
中科院分区：
文献类型：
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作者：
Xia'nan Sang;Xuedong Wan;Han Zhang;Jialiang Ying;Lu Wang;Qiao Yang;Qiyuan Shan;Min Hao;Minjing Qin;Qitong Zheng;Quan Chen;Xin Han;Gang Cao
民族药理学相关性白芍（RPA）是一种传统中药，经常用于治疗哮喘。先前的研究表明，与RPA（DCM）的二氯甲烷部分相比，炒RPA（FDCM）的二氯甲烷部分增强了抗过敏性哮喘的效果。 研究目的FDCM中观察到芍药苷（PF）、没食子酸乙酯（EG）、1,2,3,4,6-五没食子酰葡萄糖（PGG）显着增加。本研究旨在探讨FDCM中这些化合物对卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型的作用和机制。材料与方法采用中压液相色谱（MPLC）对FDCM中含量显着差异的化合物组分（FB-40）和其他组分进行富集。所有组分的药效学均在 OVA 诱导的过敏性哮喘小鼠中得到验证。此外，还探讨了 FB-40（0.42 mg/kg、0.21 mg/kg 和 0.07 mg/kg）的药物剂量依赖性，FB-40 是 FDCM 中抗过敏性哮喘最有效的部分。通过Western blot分析IL-6、p-STAT3和STAT3的表达。此外，FB-40的主要成分均通过UPLC标准鉴定。最后，采用Elisa法检测LPS刺激的BEAS-2B细胞中FB-40主要成分的抗炎作用。结果结果显示，FB-40是FDCM中活性最强的组分，可显着改善肺组织病理状况，并减少支气管肺泡灌洗液（BALF）中炎症细胞的数量。其药理活性比其主要成分PF更大。 FB-40 还在过敏性哮喘小鼠中表现出剂量依赖性并调节 IL-6/STAT3 信号通路。此外，FB-40 中的 PF、Albiflorin (AF)、PGG、EG 和 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) 均通过 UPLC 与标准品进行鉴定。最后，在LPS诱导的BEAS-2B细胞实验中，EG、PGG、1,2,3,6-Tetra-O-没食子酰-β-D-葡萄糖（TGG）比单萜苷（PF和AF）表现出更强的细胞因子抑制活性。结论研究证明FB-40是FDCM中的活性部位，通过调节IL-6/STAT3信号通路来改善过敏性哮喘。没食子酸包括TGG和PGG，以及EG也在FB-40中治疗过敏性哮喘中发挥作用。
Ethnopharmacological relevanceRadix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM).Aim of the studyThe significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model.Materials and methodsThe significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay.ResultsThe results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF).ConclusionThe research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40.