ArticleApoptosis : an international journal on programmed cell death2023
Triptolide induces PANoptosis in macrophages and causes organ injury in mice.
Article in Apoptosis : an international journal on programmed cell death, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Triptolide in renal disorders: dual roles of therapeutic potential and nephrotoxicity: a narrative review.Pharmaceutical biology · 2026Review
- Ailanthone as a novel AKT1 inhibitor that induces mitochondrial apoptosis and exerts anti-tumor activity in cervical cancer.Translational cancer research · 2026Article
- Quercetin Alleviates Triptolide-Induced Spermatogenic Dysfunction by Reducing Apoptosis and Preserving Blood-Testis Barrier Integrity in Mice.Chinese journal of integrative medicine · 2026Article
- Reprogramming of the mToxics · 2026Article
- Triptolide: A Narrative Review of Its Traditional Use, Derivatives, Pharmacology, Antitumor Effect, and Clinical Applications.Cancers · 2026Review
- Immune molecular mechanisms of PANoptosis in sepsis-induced acute kidney injury.Inflammation and regeneration · 2026Review
- Pleiotropic pharmacological activities and multiple-organ toxicities of triptolide: a programmed cell death perspective.Chinese medicine · 2026Review
- PANoptosis as a Potential Therapeutic Target in Drug-Induced Liver Injury: A Narrative Review.Journal of inflammation research · 2026Review
- Emerging role of PANoptosis in pathogen infection and systemic diseases.Cell biology and toxicology · 2025Review
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- PANoptosis: A novel therapeutic target in kidney disease (Review).International journal of molecular medicine · 2025Review
- The emerging role of mitochondria in the pharmacological and toxicological effects of Tripterygium wilfordii Hook F: functions, targets and new therapeutic applications.Chinese medicine · 2025Review
- Baicalin inhibits PANoptosis by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly in macrophages.Acta pharmacologica Sinica · 2025Article
- Targeting the programmed cell death signaling mechanism with natural products for the treatment of acute pancreatitis: a review.Frontiers in pharmacology · 2025Review
- NLRP3 Inflammasome-Mediated Pyroptosis in Diabetic Nephropathy: Pathogenic Mechanisms and Therapeutic Targets.Journal of inflammation research · 2025Review
- Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilization in macrophages.Frontiers in immunology · 2025Article
- PANoptosis in urological diseases: molecular mechanisms, pathological roles, and emerging therapeutic opportunities.Frontiers in immunology · 2025Review
- Phenylethyl isothiocyanate mitigates drug-induced liver injury in mice by inhibiting hepatocyte pyroptosis through the NLRP3-caspase-1-GSDMD pathway.Frontiers in pharmacology · 2025Article
- Article
- Identification of PANoptosis-relevant subgroups and predicting signature to evaluate the prognosis and immune landscape of patients with biliary tract cancer.Hepatology international · 2024Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages represent the first lines of innate defense against pathogenic infections and are poised to undergo multiple forms of regulated cell death (RCD) upon infections or toxic stimuli, leading to multiple organ injury. Triptolide, an active compound isolated from Tripterygium wilfordii Hook F., possesses various pharmacological activities including anti-tumor and anti-inflammatory effects, but its applications have been hampered by toxic adverse effects. It remains unknown whether and how triptolide induces different forms of RCD in macrophages. In this study, we showed that triptolide exhibited significant cytotoxicity on cultured macrophages in vitro, which was associated with multiple forms of lytic cell death that could not be fully suppressed by any one specific inhibitor for a single form of RCD. Consistently, triptolide induced the simultaneous activation of pyroptotic, apoptotic and necroptotic hallmarks, which was accompanied by the co-localization of ASC specks respectively with RIPK3 or caspase-8 as well as their interaction with each other, indicating the formation of PANoptosome and thus the induction of PANoptosis. Triptolide-induced PANoptosis was associated with mitochondrial dysfunction and ROS production. PANoptosis was also induced by triptolide in mouse peritoneal macrophages in vivo. Furthermore, triptolide caused kidney and liver injury, which was associated with systemic inflammatory responses and the activation of hallmarks for PANoptosis in vivo. Collectively, our data reveal that triptolide induces PANoptosis in macrophages in vitro and exhibits nephrotoxicity and hepatotoxicity associated with induction of PANoptosis in vivo, suggesting a new avenue to alleviate triptolide's toxicity by harnessing PANoptosis.
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