ArticleCell communication and signaling : CCS2021
Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity.
Article in Cell communication and signaling : CCS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 41 citations in OpenAlex.
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- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
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- Targeting inflammasomes as an immunotherapeutic strategy for cancer.Journal of translational medicine · 2025Review
- Evaluation on the Potential for Hepatotoxic Components from Herba Epimedii to Induce Apoptosis in HepG2 Cells and the Analysis of the Influence of Metabolism in Liver Microsomes.Molecules (Basel, Switzerland) · 2024Article
- Comprehensive review of the traditional uses and the potential benefits of epimedium folium.Frontiers in pharmacology · 2024Review
- Baohuoside I inhibits FXR signaling pathway to interfere with bile acid homeostasis via targeting ER α degradation.Cell biology and toxicology · 2023Article
- New Insights into Herb-Induced Liver Injury.Antioxidants & redox signaling · 2023Review
- Polyphenols, flavonoids and inflammasomes: the role of cigarette smoke in COPD.European respiratory review : an official journal of the European Respiratory Society · 2022Review
- Eriodictyol and Homoeriodictyol Improve Memory Impairment in AβMolecules (Basel, Switzerland) · 2022Article
- Lipoxin A4 attenuates MSU-crystal-induced NLRP3 inflammasome activation through suppressing Nrf2 thereby increasing TXNRD2.Frontiers in immunology · 2022Article
- Article
- Pharmacological effects of Chinese medicine modulating NLRP3 inflammasomes in fatty liver treatment.Frontiers in pharmacology · 2022Review
- A review of herb-induced liver injury in mainland china.Frontiers in pharmacology · 2022Review
- Immunostimulatory activity and structure-activity relationship of epimedin B fromFrontiers in pharmacology · 2022Article
- The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors.Frontiers in immunology · 2022Review
- An Integrative Pharmacology Based Analysis of Refined Liuweiwuling Against Liver Injury: A Novel Component Combination and Hepaprotective Mechanism.Frontiers in pharmacology · 2021Article
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13 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEpimedii Folium (EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI.
methodsBone-marrow-derived macrophages (BMDMs) were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1β (IL-1β) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo.
resultsIcariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mouse model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation.
conclusionsOur study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI. Video abstract.
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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.