In this study, researchers evaluated a stabilized, orally available derivative of carnosic acid (CA), a bioactive compound found in rosemary, known as diacetylated carnosic acid (diAcCA). Aimed at overcoming CA’s known limitations in stability and absorption, diAcCA was shown to convert fully into CA in the stomach and demonstrated approximately 20% improved bioavailability. Once absorbed, CA reached therapeutic levels in the brain within one hour and exhibited favourable pharmacokinetic properties without gastrointestinal toxicity.
Using a 5xFAD transgenic mouse model of Alzheimer’s disease, the study revealed that long-term oral administration of diAcCA significantly reduced amyloid plaques, tau pathology, gliosis, and neuroinflammation, while preserving neuronal and synaptic integrity. Behavioural assessments also showed improvements in memory and learning. Transcriptomic data further supported diAcCA’s anti‑inflammatory effects through modulation of the Nrf2 pathway. These findings highlight the therapeutic promise of diAcCA for Alzheimer’s disease and possibly other neurodegenerative conditions.
Reference: Banerjee, P., Y. Wang, L.N. Carnevale, P. Patel, C.K. Raspur, N. Tran, X. Zhang, et al. “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.” Antioxidants, Vol. 14, No. 3 (2025): 293. https://pmc.ncbi.nlm.nih.gov/articles/PMC11939361/