獐芽菜苦苷，一种来自川西獐牙菜的活性环烯醚萜苷，通过激活法尼醇 X 受体和胆汁酸排泄途径来预防α-萘异硫氰酸酯诱导的胆汁淤积。
Swertiamarin, an active iridoid glycoside from Swertia pseudochinensis H. Hara, protects against alpha-naphthylisothiocyanate-induced cholestasis by activating the farnesoid X receptor and bile acid excretion pathway.
机构信息
Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
Experiment Center for Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China; Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China; School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201210, China.
出版信息
J Ethnopharmacol. 2022 Jun 12;291:115164. doi: 10.1016/j.jep.2022.115164. Epub 2022 Mar 9.
ETHNOPHARMACOLOGICAL RELEVANCE
Swertiamarin (SW), which belongs to iridoid glycosides, is one of the main components of Swertia plants in Gentianaceae family, including Swertia pseudochinensis H. Hara and Swertia mileensis T. N. Ho et W. L. Shi. There are mainly used in traditional Chinese medicine for the treatment of hepatic and biliary disease such as jaundice.
AIM OF THIS STUDY
This experiment aimed to explore the protective mechanism of SW on cholestasis induced by alpha-naphthylisothiocyanate in rats.
MATERIALS AND METHODS
Healthy rats were randomly divided into the control, model (ANIT, 50 mg/kg), ursodeoxycholic acid (UDCA, 80 mg/kg), and low-dose (SW, 80 mg/kg), medium-dose (SW, 100 mg/kg), and high-dose (SW, 150 mg/kg) groups. The hepatic protective effect of SW was preliminarily evaluated by measurement of serum biochemical indicators and liver morphological evaluation. Moreover, metabolomics and proteomics analysis were used to explore the protective mechanism of SW on cholestasis. The expression of related proteins was determined by Western blot and polymerase chain reaction, and the important proteins were verified by cell experiments in vitro.
RESULTS
SW (100 mg/kg) can reduce the serum levels of the model group. The hepatocyte of the medium-dose treatment group was arranged neatly without evident inflammation. SW can partially reverse the changes in cholestasis metabolites, such as taurocholic acid, SM (d18:1/16:0), all-trans-retinoic acid and other products of rats. The main metabolic pathways affected were primary bile acid synthesis, glycerophospholipid metabolism, sphingolipid metabolism and retinol metabolism. SW medium-dose treatment group showed effective reversal of 25 related proteins and it can remarkably reduce the contents of NTCP and CYP27A1 in rat liver and increase the protein expressions of CYP7A1, CYP8B1, bile salt export pump, multidrug resistance-associated protein and FXR.
CONCLUSIONS
SW can alleviate ANIT-induced cholestasis, which by activating the farnesoid X receptor and bile acid excretion pathway.
民族药理学相关性
獐牙菜苦苷（SW）属于环烯醚萜苷类，是龙胆科獐牙菜属植物的主要成分之一，包括川西獐牙菜 H. Hara 和川西獐牙菜 T. N. Ho 等。它们主要用于治疗黄疸等肝胆疾病。
本研究目的
本实验旨在探讨 SW 对α-萘异硫氰酸酯诱导的大鼠胆汁淤积的保护机制。
材料和方法
健康大鼠随机分为对照组、模型组（ANIT，50mg/kg）、熊去氧胆酸（UDCA，80mg/kg）和低剂量（SW，80mg/kg）、中剂量（SW，100mg/kg）和高剂量（SW，150mg/kg）组。通过测定血清生化指标和肝脏形态学评价，初步评价 SW 的肝保护作用。此外，还采用代谢组学和蛋白质组学分析方法探讨 SW 对胆汁淤积的保护机制。通过 Western blot 和聚合酶链反应测定相关蛋白的表达，通过体外细胞实验验证重要蛋白。
结果
SW（100mg/kg）可降低模型组血清水平。中剂量治疗组的肝细胞排列整齐，无明显炎症。SW 可部分逆转胆汁淤积代谢物的变化，如牛磺胆酸、SM（d18：1/16：0）、全反式视黄酸等大鼠产物。受影响的主要代谢途径是初级胆汁酸合成、甘油磷脂代谢、鞘脂代谢和视黄醇代谢。SW 中剂量治疗组显示 25 种相关蛋白的有效逆转，可显著降低大鼠肝内 NTCP 和 CYP27A1 的含量，增加 CYP7A1、CYP8B1、胆汁盐输出泵、多药耐药相关蛋白和 FXR 的蛋白表达。
结论
SW 可缓解 ANIT 诱导的胆汁淤积，其机制可能是通过激活法尼醇 X 受体和胆汁酸排泄途径。
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