ArticleApoptosis : an international journal on programmed cell death2019
The neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy that depends on HDAC and AhR/CYP1A1 but not ERα/CYP19A1 signaling.
Article in Apoptosis : an international journal on programmed cell death, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Modulation of miRNAs by Phytochemicals in Cerebral Ischemia: A Systematic Review of In Vitro and In Vivo Studies.Phytotherapy research : PTR · 2025Pooled it
- Indole-Derived Compounds as Redox-Modulators: Antioxidant Mechanisms in Neuronal Protection.Molecules (Basel, Switzerland) · 2026Review
- Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions.Nature aging · 2026Article
- Network pharmacology-based discovery and experimental validation of novel drug repurposing candidates in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- A "One-Stone-Three-Birds" Inspired Nanoplatform for Multitargeted Ulcerative Colitis Therapy via Combined Aryl Hydrocarbon Receptor Activation and Reactive Oxygen Species Scavenging.Biomaterials research · 2026Article
- Aryl hydrocarbon receptor regulates programmed cell death in diseases: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The Aryl Hydrocarbon Receptor in Neurotoxicity: An Intermediator Between Dioxins and Neurons in the Brain.Toxics · 2025Review
- Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review.Plants (Basel, Switzerland) · 2025Review
- Famciclovir Ameliorates Platelet Activation and Thrombosis by AhR-Regulated Autophagy.Cardiovascular toxicology · 2025Article
- 3,3'-Diindolylmethane improves pathology and neurological outcome following traumatic brain injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Amorfrutin B Compromises Hypoxia/Ischemia-induced Activation of Human Microglia in a PPARγ-dependent Manner: Effects on Inflammation, Proliferation Potential, and Mitochondrial Status.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Posttreatment with Ospemifene Attenuates Hypoxia- and Ischemia-Induced Apoptosis in Primary Neuronal Cells via Selective Modulation of Estrogen Receptors.Neurotoxicity research · 2023Article
- Synthetic Methodologies and Therapeutic Potential of Indole-3-Carbinol (I3C) and Its Derivatives.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity.Cell death discovery · 2022Article
- Diindolylmethane Inhibits Cadmium-Induced Autophagic Cell Death via Regulation of Oxidative Stress in HEL299 Human Lung Fibroblasts.Molecules (Basel, Switzerland) · 2022Article
- Effective Synthesis and Biological Evaluation of Natural and Designed Bis(indolyl)methanes via Taurine-Catalyzed Green Approach.ACS omega · 2022Article
- Diindolylmethane Ameliorates Ischemic Stroke-Induced Brain Injury by Peripheral and Central Mechanisms.Current neurovascular research · 2022Article
- Host-microbiota interactions: The aryl hydrocarbon receptor in the acute and chronic phases of cerebral ischemia.Frontiers in immunology · 2022Review
- Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases.International journal of molecular sciences · 2021Review
- Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain.International journal of molecular sciences · 2021Article
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5 authors at 1 institution in 1 country.
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Abstract
There are no studies examining the effects of 3,3'-diindolylmethane (DIM) in neuronal cells subjected to ischemia. Little is also known about the roles of apoptosis and autophagy as well as AhR and ERα signaling and HDACs in DIM action. We demonstrated for the first time the strong neuroprotective capacity of DIM in mouse primary hippocampal cell cultures exposed to ischemia at early and later stages of neuronal development. The protective effects of DIM were mediated via inhibition of ischemia-induced apoptosis and autophagy that was accompanied by a decrease in AhR/CYP1A1 signaling and an increase in HDAC activity. DIM decreased the levels of pro-apoptotic factors, i.e., Fas, Caspase-3, and p38 mitogen-activated protein kinase (MAPK). DIM also reduced the protein levels of autophagy-related Beclin-1 (BECN1) and microtubule-associated proteins 1A/1B light chain (LC3), partially reversed the ischemia-induced decrease in Nucleoporin 62 (NUP62) and inhibited autophagosome formation. In addition, DIM completely reversed the ischemia-induced decrease in histone deacetylase (HDAC) activity in hippocampal neurons. Although DIM inhibited AhR/CYP1A1 signaling, it did not influence the protein expression levels of ERα and ERα-regulated CYP19A1 which are known to be controlled by AhR. This study demonstrated for the first time, that the neuroprotective action of 3,3'-diindolylmethane against ischemia involves an inhibition of apoptosis and autophagy and depends on AhR/CYP1A1 signaling and HDAC activity, thus creating the possibility of developing new therapeutic strategies that target neuronal degeneration at specific molecular levels.
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