ArticleAntioxidants (Basel, Switzerland)2025
diAcCA, a Pro-Drug for Carnosic Acid That Activates the Nrf2 Transcriptional Pathway, Shows Efficacy in the 5xFAD Transgenic Mouse Model of Alzheimer's Disease.
Article in Antioxidants (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- Unravelling the phytochemical complexity of neuroprotective plants: a metabolomics approach to Alzheimer's disease.Molecular biology reports · 2026Review
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Multitarget Actions of Pentacyclic Triterpenic Acids in Alzheimer's Disease: Mechanistic Insights.Molecules (Basel, Switzerland) · 2026Review
- Aberrant Protein S-Nitrosylation Mimics the Effect of Rare Genetic Mutations in Neurodegenerative Diseases.Journal of neurochemistry · 2026Review
- Rosemary (Iranian journal of basic medical sciences · 2026Review
- The transcriptional and cellular landscape of cognitive resilience to Alzheimer's disease.Frontiers in molecular neuroscience · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
The antioxidant/anti-inflammatory compound carnosic acid (CA) is a phenolic diterpene found in the herbs rosemary and sage. Upon activation, CA manifests electrophilic properties to stimulate the Nrf2 transcriptional pathway via reaction with Keap1. However, purified CA is readily oxidized and thus highly unstable. To develop CA as an Alzheimer's disease (AD) therapeutic, we synthesized pro-drug derivatives, among which the di-acetylated form (diAcCA) showed excellent drug-like properties. diAcCA converted to CA in the stomach prior to absorption into the bloodstream, and exhibited improved stability and bioavailability as well as comparable pharmacokinetics (PK) and efficacy to CA. To test the efficacy of diAcCA in AD transgenic mice, 5xFAD mice (or littermate controls) received the drug for 3 months, followed by behavioral and immunohistochemical studies. Notably, in addition to amyloid plaques and tau tangles, a hallmark of human AD is synapse loss, a major correlate to cognitive decline. The 5xFAD animals receiving diAcCA displayed synaptic rescue on immunohistochemical analysis accompanied by improved learning and memory in the water maze test. Treatment with diAcCA reduced astrocytic and microglial inflammation, amyloid plaque formation, and phospho-tau neuritic aggregates. In toxicity studies, diAcCA was as safe or safer than CA, which is listed by the FDA as "generally regarded as safe", indicating diAcCA is suitable for human clinical trials in AD.
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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.