18β-Glycyrrhetinic Acid Protects against Cholestatic Liver Injury in Bile Duct-Ligated Rats

Abstract

18β-Glycyrrhetinic acid is a nutraceutical agent with promising hepatoprotective effects. Its protective mechanisms against cholestatic liver injury were further investigated in a rodent model of extrahepatic cholestasis caused by Bile Duct Ligation (BDL) in rats. The daily oral administration of 18β-Glycyrrhetinic acid improved liver histology, serum biochemicals, ductular reaction, oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis. 18β-Glycyrrhetinic acid alleviated the BDL-induced hepatic and systemic retention of bile acids, matrix-producing cell activation, hepatic collagen deposition, Transforming Growth Factor beta-1/Smad activation, malondialdehyde elevation, glutathione reduction, High Mobility Group Box-1/Toll-Like Receptor-4 activation, NF-κB activation, inflammatory cell infiltration/accumulation, Interleukin-1β expression, Signal Transducer and Activator of Transcription-1 activation, Endoplasmic Reticulum stress, impairment autophagy, and caspase 3 activation. Conversely, the protein expression of Sirt1, Farnesoid X Receptor, nuclear NF-E2-Related Factor-2, Transcription Factor EB, bile acid efflux transporters, and LC3-II, as well as the protein phosphorylation of AMP-Activated Protein Kinase, was promoted in 18β-Glycyrrhetinic acid-treated BDL rats. The hepatoprotective effects of 18β-Glycyrrhetinic acid in the present investigation correlated well with co-activation and possible interactions among Sirt, FXR, and Nrf2. The concurrent or concomitant activation of Sirt1, FXR, and Nrf2 not only restored the homeostatic regulation of bile acid metabolism, but also alleviated oxidative stress, inflammation, apoptosis, impaired autophagy, and fibrosis.

Quantitative proteomics reveals the protective effects of Yinchenzhufu decoction against cholestatic liver fibrosis in mice by inhibiting the PDGFRβ/PI3K/AKT pathway

“…Among these plant metabolites, chlorogenic acid, scoparone, isoliquiritigenin, glycyrrhetinic acid, formononetin, atractylenolide I, and benzoylaconitine exhibited inhibitory effects on PDGFRβ mRNA expression. Previous studies reported that chlorogenic acid, scoparone, liquiritigenin, and glycyrrhetinic acid exhibit hepatoprotective effects against liver fibrosis ( Hui et al, 2020 ; Wang et al, 2021c ; Miao et al, 2022 ; Pan et al, 2022 ). These active plant metabolites may contribute to the protective effect of YCZFD against DDC-induced CLF by regulating PDGFRβ.…”

Analysis and Validation of the Network Pharmacology of the Mechanism of Glycyrrhetinic Acid for the Treatment of High-Altitude Pulmonary Hypertension

“…Glycyrrhetinic acid (GA), which has an oleanolane-type skeleton, is a pentacyclic triterpene component in Glycyrrhize glabra L extract, a traditional Chinese medicine, and is widely distributed in nature. With multiple biological activities such as anti-infammatory [1], anti-tumor [2,3], antioxidant [4], liver protection [5,6], and enhanced cellular immune regulation [7], GA has signifcant curative efects on ventricular arrhythmias induced by various reasons, can protect myocardium, and can reduce myocardial ischemic damage for acute myocardial infarction [8]. Te biological role of GA in improving lung function has been confrmed.…”

Comparison of pharmacokinetic profiles of seven major bioactive components in normal and non-alcoholic fatty liver disease (NAFLD) rats after oral administration of Ling-Gui-Zhu-Gan decoction by UPLC-MS/MS

“…It has been revealed that the function of carbohydrate transport and metabolism is significantly decreased by glycyrrhizic acid. Glycyrrhetinic acid prevents cholestatic liver injury in bile duct–ligated rats, while liquiritin alleviates cyclophosphamide-induced liver sinusoidal endothelial injury and inflammatory injury in mice ( Chen M. et al, 2019 ; Pan et al, 2022 ; Wang et al, 2022 ). Poria cocos (Schw.)…”