ArticleCell death & disease2021
Prevention of D-GalN/LPS-induced ALI by 18β-glycyrrhetinic acid through PXR-mediated inhibition of autophagy degradation.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- Pregnane X receptor mitigates aristolochic acid-induced acute kidney injury via p53 ubiquitination.Renal failure · 2026Article
- Formulation and in vitro-in vivo assessment of a novel monoammonium glycyrrhizinate controlled-porosity osmotic pump.Scientific reports · 2026Article
- 18β-Glycyrrhetinic Acid and a Nano-Liposomal Formulation Alleviate Depression-Like Behaviors via the Microglial mTOR-Autophagy-NLRP3 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Glycyrrhizin preparations in liver diseases: a narrative review of mechanisms and therapeutic potential.Frontiers in pharmacology · 2026Review
- Pregnane X receptor alleviates sepsis-induced liver injury through activation of yes-associated protein in mice.Acta pharmacologica Sinica · 2025Article
- Dust Fall Microplastics from a Megacity of China Inhibit Autophagy via the PI3K/Akt/mTOR Pathway.Environment & health (Washington, D.C.) · 2025Article
- Human adenovirus type 7 (HAdV-7) infection induces pulmonary vascular endothelial injury through the activation of endothelial autophagy.Respiratory research · 2024Article
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Review
- A review of typical biological activities of glycyrrhetinic acid and its derivatives.RSC advances · 2024Review
- Avicularin alleviates acute liver failure by regulation of the TLR4/MyD88/NF-κB and Nrf2/HO-1/GPX4 pathways to reduce inflammation and ferroptosis.Journal of cellular and molecular medicine · 2023Article
- Pharmacological Features of 18β-Glycyrrhetinic Acid: A Pentacyclic Triterpenoid of Therapeutic Potential.Plants (Basel, Switzerland) · 2023Review
- Natural-Product-Mediated Autophagy in the Treatment of Various Liver Diseases.International journal of molecular sciences · 2022Review
- Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice).Liver research (Beijing, China) · 2022Article
- LncRNA-Airn alleviates acute liver injury by inhibiting hepatocyte apoptosis via the NF-κB signaling pathway.Acta biochimica et biophysica Sinica · 2022Article
- Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II).International journal of molecular sciences · 2022Review
- Review
- Hepatoprotective Effects of Glycyrrhetinic Acid on Lithocholic Acid-Induced Cholestatic Liver Injury Through Choleretic and Anti-Inflammatory Mechanisms.Frontiers in pharmacology · 2022Article
- Sunitinib induced hepatotoxicity in L02 cellsFrontiers in pharmacology · 2022Article
- Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Frontiers in endocrinology · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute liver injury (ALI) has multiple causes and results in liver dysfunction. Severe or persistent liver injury eventually leads to liver failure and even death. Pregnane X receptor (PXR)-null mice present more severe liver damage and lower rates of autophagy. 18β-glycyrrhetinic acid (GA) has been proposed as a promising hepatoprotective agent. We hypothesized that GA significantly alleivates D-GalN/LPS-induced ALI, which involved in PXR-mediated autophagy and lysosome biogenesis. We found that GA can significantly decrease hepatocyte apoptosis and increase the hepatic autophagy marker LC3-B. Ad-mCherry-GFP-LC3 tandem fluorescence, RNA-seq and real-time PCR indicated that GA may stabilize autophagosomes and lysosomes and inhibit autophagosome-lysosome fusion. Simultaneously, GA markedly activates PXR, even reversing the D-GalN/LPS-induced reduction of PXR and its downstream genes. In contrast, GA has a weak protective effect in pharmacological inhibition of PXR and PXR-null mice, which significantly affected apoptosis- and autophagy-related genes. PXR knockout interferes with the stability of autophagosomes and lysosomes, preventing GA reducing the expression of lysosomal genes such as Cst B and TPP1, and suppressing autophagy flow. Therefore, we believe that GA increases autophagy by inhibiting autophagosome-lysosome fusion and blocked autophagy flux via activation of PXR. In conclusion, our results show that GA activates PXR to regulate autophagy and lysosome biogenesis, represented by inhibiting autophagosome-lysosome fusion and stabilization of lysosome. These results identify a new mechanism by which GA-dependent PXR activation reduces D-GalN/LPS-induced acute liver injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.