Naunyn-Schmiedeberg's Archives of Pharmacology ( IF 3.1 ) Pub Date : 2023-10-09 , DOI: 10.1007/s00210-023-02733-w Xing Wang 1 , Wenqiang Xiong 1 , Xin Wang 1 , Liying Qin 1 , Maolian Zhong 1 , Yan Liu 1 , Yuqing Xiong 1 , Xiaoyi Yi 2 , Xiaosong Wang 2 , Hong Zhang 2, 3
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Ursolic acid (UA), a pentacyclic triterpenoid, exhibits various pharmacological actions, such as anti-inflammation, anti-tumor, anti-diabetes, heart protection, and liver protection. However, the role of nuclear factor E2-related factor 2 (NRF2)-mediated regulation of uridine diphosphate glucuronosyltransferase (UGT2B7) and bile salt export pump (BSEP)/multidrug resistance-associated protein 2 (MRP2) in UA against cholestatic liver injury has not been cleared. The purpose of this study is to explore the effect of UA on cholestatic liver injury and its potential mechanism. The results of the liver pathology sections and blood biochemical indices demonstrated that UA significantly attenuated the cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) in a dose-dependent manner. The mRNA and protein levels of UGT2B7 and BSEP/MRP2 were remarkably increased in the liver of ANIT rats and HepG2 cells pretreated with UA, but this activation was suppressed with NRF2 silenced. In conclusion, our findings demonstrate that UA prevents cholestasis, which may be associated with NRF2-mediated regulation of UGT2B7, BSEP/MRP2.
Graphical Abstract
中文翻译：
熊果酸通过 NRF2 介导的 UGT2B7 和 BSEP/MRP2 调节减轻胆汁淤积
熊果酸（UA）是一种五环三萜类化合物，具有抗炎、抗肿瘤、抗糖尿病、保护心脏、保护肝脏等多种药理作用。然而，核因子E2相关因子2（NRF2）介导的尿苷二磷酸葡萄糖醛酸基转移酶（UGT2B7）和胆汁盐输出泵（BSEP）/多药耐药相关蛋白2（MRP2）的调节在UA对抗胆汁淤积性肝损伤中的作用已被证实。没有被清除。本研究的目的是探讨UA对胆汁淤积性肝损伤的影响及其潜在机制。肝脏病理切片和血液生化指标结果表明，UA以剂量依赖性方式显着减轻α-萘基异硫氰酸酯（ANIT）引起的胆汁淤积性肝损伤。在用UA预处理的ANIT大鼠和HepG2细胞的肝脏中，UGT2B7和BSEP/MRP2的mRNA和蛋白水平显着增加，但这种激活被NRF2沉默所抑制。总之，我们的研究结果表明，UA 可预防胆汁淤积，这可能与 NRF2 介导的 UGT2B7、BSEP/MRP2 调节有关。
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