Ursolic acid attenuates cholestasis through NRF2-mediated regulation of UGT2B7 and BSEP/MRP2

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:397

Enthalten in:

Naunyn-Schmiedeberg's archives of pharmacology - 397(2024), 4 vom: 29. März, Seite 2257-2267

Sprache:

Englisch

Beteiligte Personen:

Wang, Xing [VerfasserIn]
Xiong, Wenqiang [VerfasserIn]
Wang, Xin [VerfasserIn]
Qin, Liying [VerfasserIn]
Zhong, Maolian [VerfasserIn]
Liu, Yan [VerfasserIn]
Xiong, Yuqing [VerfasserIn]
Yi, Xiaoyi [VerfasserIn]
Wang, Xiaosong [VerfasserIn]
Zhang, Hong [VerfasserIn]

Links:

Volltext

Themen:

ATP Binding Cassette Transporter, Subfamily B, Member 11
BSEP
Cholestasis
Journal Article
MRP2
Multidrug Resistance-Associated Protein 2
NF-E2-Related Factor 2
NRF2
P3M2575F3F
Research Support, Non-U.S. Gov't
UGT2B7
Ursolic Acid
Ursolic acid

Anmerkungen:

Date Completed 14.03.2024

Date Revised 18.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s00210-023-02733-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36305412X