School of Pharmaceutical, Nanchang University, Nanchang, 330006, China.
Clinical Medicine Research Center, Jiangxi Cancer Hospital (The Second Affiliated Hospital of Nanchang Medical College), Nanchang, 330029, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Apr;397(4):2257-2267. doi: 10.1007/s00210-023-02733-w. Epub 2023 Oct 9.
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.
熊果酸（UA）是一种五环三萜，具有多种药理作用，如抗炎、抗肿瘤、抗糖尿病、心脏保护和肝脏保护。然而，核因子 E2 相关因子 2（NRF2）介导的调节尿苷二磷酸葡萄糖醛酸转移酶（UGT2B7）和胆汁盐输出泵（BSEP）/多药耐药相关蛋白 2（MRP2）在 UA 对抗胆汁淤积性肝损伤中的作用尚不清楚。本研究旨在探讨 UA 对胆汁淤积性肝损伤的作用及其潜在机制。肝组织病理学切片和血液生化指标的结果表明，UA 可显著抑制α-萘异硫氰酸酯（ANIT）诱导的胆汁淤积性肝损伤，呈剂量依赖性。UGT2B7 和 BSEP/MRP2 的 mRNA 和蛋白水平在 ANIT 大鼠肝脏和 UA 预处理的 HepG2 细胞中显著增加，但这种激活被 NRF2 沉默抑制。综上所述，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。
