ArticleActa pharmacologica Sinica2019
Quercetin attenuates toosendanin-induced hepatotoxicity through inducing the Nrf2/GCL/GSH antioxidant signaling pathway.
Article in Acta pharmacologica Sinica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 91 citations in OpenAlex.
- Toosendanin suppresses acute myeloid leukemia by targeting DDX5/c-Myc axis to inhibit protein synthesis.Journal of translational medicine · 2026Article
- Melatonin and Selected Phytochemicals: A Promising Combination to Target Altered Metabolism in Cancer.Nutrients · 2026Review
- Metabolic Symbiosis Between Cancer Cells and Endothelial Cells: A Key Driver of Tumor Angiogenesis.Advances in experimental medicine and biology · 2026Review
- Flavonoids from Polygonum hydropiper L. regulate PCV2-induced oxidative stress of RAW264.7 cells via Pi3k/AKT and Nrf2/HO-1 signaling pathways.Scientific reports · 2025Article
- Toosendanin Induces Hepatotoxicity by Facilitating ALOX5-Mediated Lipid Peroxidation and Sensitizing Cells to Ferroptosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The protective effects of propolis against lipopolysaccharide-induced acute liver injury by modulating serum metabolites and gut flora.Scientific reports · 2025Article
- Natural Products as Novel Therapeutic Agents for Triple-Negative Breast Cancer: Current Evidence, Mechanisms, Challenges, and Opportunities.Molecules (Basel, Switzerland) · 2025Review
- Ferroptosis and Intrinsic Drug-induced Liver Injury by Acetaminophen and Other Drugs: A Critical Evaluation and Historical Perspective.Journal of clinical and translational hepatology · 2024Review
- New perspectives on the therapeutic potential of quercetin in non-communicable diseases: Targeting Nrf2 to counteract oxidative stress and inflammation.Journal of pharmaceutical analysis · 2024Review
- Dietary Polyphenols: Review on Chemistry/Sources, Bioavailability/Metabolism, Antioxidant Effects, and Their Role in Disease Management.Antioxidants (Basel, Switzerland) · 2024Review
- Flavonoids in natural products for the therapy of liver diseases: progress and future opportunities.Frontiers in pharmacology · 2024Review
- Sugarcane leaf polysaccharide exerts a therapeutic effect on cardiovascular diseases through necroptosis.Heliyon · 2023Article
- Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies.International journal of molecular sciences · 2023Review
- Isolation and Characterization of an Anti-Osteoporotic Compound fromPharmaceutics · 2023Article
- Isotoosendanin exerts inhibition on triple-negative breast cancer through abrogating TGF-Acta pharmaceutica Sinica. B · 2023Article
- Radix Paeoniae Alba attenuates Radix Bupleuri-induced hepatotoxicity by modulating gut microbiota to alleviate the inhibition of saikosaponins on glutathione synthetase.Journal of pharmaceutical analysis · 2023Article
- Azithromycin ameliorated cigarette smoke-induced airway epithelial barrier dysfunction by activating Nrf2/GCL/GSH signaling pathway.Respiratory research · 2023Article
- Article
- Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis.Acta pharmaceutica Sinica. B · 2023Article
- Cycloartenyl Ferulate Is the Predominant Compound in Brown Rice Conferring Cytoprotective Potential against Oxidative Stress-Induced Cytotoxicity.International journal of molecular sciences · 2023Article
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7 authors at 2 institutions in 1 country.
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Abstract
Toosendanin (TSN) is the main active compound in Toosendan Fructus and Meliae Cortex, two commonly used traditional Chinese medicines. TSN has been reported to induce hepatotoxicity, but its mechanism remains unclear. In this study, we demonstrated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in protecting against TSN-induced hepatotoxicity in mice and human normal liver L-02 cells. In mice, administration of TSN (10 mg/kg)-induced acute liver injury evidenced by increased serum alanine/aspartate aminotransferase (ALT/AST) and alkaline phosphatase (ALP) activities, and total bilirubin (TBiL) content as well as the histological changes. Furthermore, TSN markedly increased liver reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and decreased liver glutathione (GSH) content and Nrf2 expression. In L-02 cells, TSN (2 μM) time-dependently reduced glutamate-cysteine ligase (GCL) activity and cellular expression of the catalytic/modify subunit of GCL (GCLC/GCLM). Moreover, TSN reduced cellular GSH content and the increased ROS formation, and time-dependently decreased Nrf2 expression and increased the expression of the Nrf2 inhibitor protein kelch-like ECH-associated protein-1 (Keap1). Pre-administration of quercetin (40, 80 mg/kg) effectively inhibited TSN-induced liver oxidative injury and reversed the decreased expression of Nrf2 and GCLC/GCLM in vivo and in vitro. In addition, the quercetin-provided protection against TSN-induced hepatotoxicity was diminished in Nrf2 knock-out mice. In conclusion, TSN decreases cellular GSH content by reducing Nrf2-mediated GCLC/GCLM expression via decreasing Nrf2 expression. Quercetin attenuates TSN-induced hepatotoxicity by inducing the Nrf2/GCL/GSH antioxidant signaling pathway. This study implies that inducing Nrf2 activation may be an effective strategy to prevent TSN-induced hepatotoxicity.
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