ArticleMolecular pharmaceutics2022
L-type Amino Acid Transporter 1 Utilizing Ferulic Acid Derivatives Show Increased Drug Delivery in the Mouse Pancreas Along with Decreased Lipid Peroxidation and Prostaglandin Production.
Article in Molecular pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- LAT1-mediated delivery of engineered R13A-MOTS-c attenuates radiation-induced lung injury via Nrf2 activation and mitochondrial protection.Redox biology · 2026Article
- Preclinical Evaluation of 5F-αMe-3BPA for Improving Pharmacokinetics in Boron Neutron Capture Therapy.Pharmaceutics · 2026Article
- Dexborneol Amplifies Pregabalin's Analgesic Effect in Mouse Models of Peripheral Nerve Injury and Incisional Pain.Antioxidants (Basel, Switzerland) · 2024Article
- Exploring the mechanism of metformin action in Alzheimer's disease and type 2 diabetes based on network pharmacology, molecular docking, and molecular dynamic simulation.Therapeutic advances in endocrinology and metabolism · 2023Article
- Aminopeptidase B can bioconvert L-type amino acid transporter 1 (LAT1)-utilizing amide prodrugs in the brain.Frontiers in pharmacology · 2022Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
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Abstract
Oxidative stress and pathological changes of Alzheimer's disease (AD) overlap with metabolic diseases, such as diabetes mellitus (DM). Therefore, tackling oxidative stress with antioxidants is a compelling drug target against multiple chronic diseases simultaneously. Ferulic acid (FA), a natural antioxidant, has previously been studied as a therapeutic agent against both AD and DM. However, FA suffers from poor bioavailability and delivery. As a solution, we have previously reported about L-type amino acid transporter 1 (LAT1)-utilizing derivatives with increased brain delivery and efficacy. In the present study, we evaluated the pharmacokinetics and antioxidative efficacy of the two derivatives in peripheral mouse tissues. Furthermore, we quantified the LAT1 expression in studied tissues with a targeted proteomics method to verify the transporter expression in mouse tissues. Additionally, the safety of the derivatives was assessed by exploring their effects on hemostasis in human plasma, erythrocytes, and endothelial cells. We found that both derivatives accumulated substantially in the pancreas, with over a 100-times higher area under curve compared to the FA. Supporting the pharmacokinetics, the LAT1 was highly expressed in the mouse pancreas. Treating mice with the LAT1-utilizing derivative of FA lowered malondialdehyde and prostaglandin E
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