ArticleInternational journal of molecular sciences2023
Protective Effect of Water-Soluble Acacetin Prodrug on APAP-Induced Acute Liver Injury Is Associated with Upregulation of PPARγ and Alleviation of ER Stress.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Zingerone Alleviates Acetaminophen-Induced Liver Damage by Regulating Oxidative Stress, Inflammation, Apoptosis, Endoplasmic Reticulum Stress, and Autophagy.Journal of biochemical and molecular toxicology · 2026Article
- Edible Fungus Compound Cordycepin Protects Against Acetaminophen-Induced Liver Injury.Journal of clinical laboratory analysis · 2026Article
- Enhancement of the Anti-Hepatoma Activity of Acacetin Through Salt Formation of Sodium Acacetin.Chemistry & biodiversity · 2026Article
- 5-Azacytidine inhibits endoplasmic reticulum stress and apoptosis of nucleus pulposus cells by preserving PPARγ via promoter demethylation.In vitro cellular & developmental biology. Animal · 2025Article
- The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Acacetin as a natural cardiovascular therapeutic: mechanisms and preclinical evidence.Frontiers in pharmacology · 2025Review
- Hepatoprotective Effects of Gac (Journal of experimental pharmacology · 2025Article
- Acacetin, a Natural Flavone with Potential in Improving Liver Disease Based on Its Anti-Inflammation, Anti-Cancer, Anti-Infection and Other Effects.Molecules (Basel, Switzerland) · 2024Review
- Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2024Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
A water-soluble acacetin prodrug has been synthesized and reported by our group previously. Acetaminophen (APAP) overdose is a leading cause of acute liver injury. We found that subcutaneous injection of acacetin prodrug (5, 10, 20 mg/kg) decreased serum ALT, AST, and ALP, corrected the abnormal MDA and GSH in liver, and improved intrahepatic hemorrhage and destruction of liver structures in APAP (300 mg/kg)-treated mice. Molecular mechanism analysis revealed that the expressions of endoplasmic reticulum (ER) stress markers ATF6, CHOP, and p-PERK, apoptosis-related protein BAX, and cleaved caspase 3 were decreased by acacetin in a dose-dependent manner in vivo and in vitro. Moreover, via the acacetin-upregulated peroxisome-proliferator-activated receptor gamma (PPARγ) of HepG2 cells and liver, the suppressive effect of acacetin on ER stress and apoptosis was abolished by PPARγ inhibitor (GW9662) or PPARγ-siRNA. Molecular docking revealed that acacetin can bind to three active pockets of PPARγ, mainly by hydrogen bond. Our results provide novel evidence that acacetin prodrug exhibits significant protective effect against APAP-induced liver injury by targeting PPARγ, thereby suppressing ER stress and hepatocyte apoptosis. Acacetin prodrug is likely a promising new drug candidate for treating patients with acute liver injury induced by APAP.
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Registered trials
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