ArticleAmerican journal of human genetics2020
Apigenin as a Candidate Prenatal Treatment for Trisomy 21: Effects in Human Amniocytes and the Ts1Cje Mouse Model.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 25 citations in OpenAlex.
- Fasudil induces anti-inflammatory transcriptomic changes and increased proliferation in human trisomy 21 neural progenitor cells.Biology open · 2026Article
- From classroom to the counter: exploring knowledge, attitudes, and practices toward Down syndrome among pharmacy students and pharmacists.BMC medical education · 2026Article
- Opportunities for antenatal medical treatment of genetic conditions: the earlier, the better.Pediatric research · 2026Article
- Loss of Proteostasis and Early-Onset Neurodegeneration in Down Syndrome: From Mechanisms to Interventions.Antioxidants (Basel, Switzerland) · 2026Review
- Anti-inflammatory and pro-proliferative effects of fasudil in human trisomy 21 neural progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Targeting senescence-associated secretory phenotype macrophage: apigenin inhibits DOT1L-dependent H3K79me2 atFrontiers in molecular biosciences · 2026Article
- Investigating the Origins of Biochemical Dysregulation in Trisomy 21 Pregnancy.The Journal of clinical endocrinology and metabolism · 2025Article
- Reviewing the possible connection between cerebral amyloid angiopathy and blood-brain barrier integrity in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Therapeutic targeting of the tryptophan-kynurenine-aryl hydrocarbon receptor pathway with apigenin in MED12-mutant leiomyoma cells.Cancer gene therapy · 2025Article
- Metformin modulates oxidative stress via activation of AMPK/NF-κB signaling in Trisomy 21 fibroblasts: anFrontiers in molecular biosciences · 2025Article
- The Role of Oxidative Stress in Trisomy 21 Phenotype.Cellular and molecular neurobiology · 2023Review
- Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition.Science advances · 2023Article
- Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model.Nature genetics · 2023Article
- Visual discrimination and inhibitory control deficits in mouse models of Down syndrome: A pilot study using rodent touchscreen technology.Journal of neuroscience research · 2023Article
- Application of regulation of reactive oxygen species and lipid peroxidation to disease treatment.Journal of clinical biochemistry and nutrition · 2023Article
- IGF1 deficiency integrates stunted growth and neurodegeneration in Down syndrome.Cell reports · 2022Article
- Studies on Apigenin and Its Biological and Pharmacological Activity in Brain Disorders.Advanced pharmaceutical bulletin · 2022Article
- Future Perspectives in Oxidative Stress in Trisomy 13 and 18 Evaluation.Journal of clinical medicine · 2022Review
- The Challenging Pathway of Treatment for Neurogenesis Impairment in Down Syndrome: Achievements and Perspectives.Frontiers in cellular neuroscience · 2022Review
- Impaired Brain Mitochondrial Bioenergetics in the Ts65Dn Mouse Model of Down Syndrome Is Restored by Neonatal Treatment with the Polyphenol 7,8-Dihydroxyflavone.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Human fetuses with trisomy 21 (T21) have atypical brain development that is apparent sonographically in the second trimester. We hypothesize that by analyzing and integrating dysregulated gene expression and pathways common to humans with Down syndrome (DS) and mouse models we can discover novel targets for prenatal therapy. Here, we tested the safety and efficacy of apigenin, identified with this approach, in both human amniocytes from fetuses with T21 and in the Ts1Cje mouse model. In vitro, T21 cells cultured with apigenin had significantly reduced oxidative stress and improved antioxidant defense response. In vivo, apigenin treatment mixed with chow was administered prenatally to the dams and fed to the pups over their lifetimes. There was no significant increase in birth defects or pup deaths resulting from prenatal apigenin treatment. Apigenin significantly improved several developmental milestones and spatial olfactory memory in Ts1Cje neonates. In addition, we noted sex-specific effects on exploratory behavior and long-term hippocampal memory in adult mice, and males showed significantly more improvement than females. We demonstrated that the therapeutic effects of apigenin are pleiotropic, resulting in decreased oxidative stress, activation of pro-proliferative and pro-neurogenic genes (KI67, Nestin, Sox2, and PAX6), reduction of the pro-inflammatory cytokines INFG, IL1A, and IL12P70 through the inhibition of NFκB signaling, increase of the anti-inflammatory cytokines IL10 and IL12P40, and increased expression of the angiogenic and neurotrophic factors VEGFA and IL7. These studies provide proof of principle that apigenin has multiple therapeutic targets in preclinical models of DS.
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Registered trials
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.