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Magnolol, which is a CYP3A substrate, is a well-known agent that can facilitate neuroprotection and reduce ischemic brain damage. However, a well-controlled release formulation is needed for the effective delivery of magnolol due to its poor water solubility. In this study, we have developed a formulation for a CYP3A-excipient microemulsion, which can be administrated intraperitoneally to increase the solubility and bioavailability of magnolol and increase its neuroprotective effect against ischemic brain injury. The results showed a significant improvement in the area under the plotted curve of drug concentration versus time curve (AUC0-t) and mean residence time (MRT) of magnolol in microemulsion compared to when it was dissolved in dimethyl sulfoxide (DMSO). Both magnolol in DMSO and microemulsion, administrated after the onset of ischemia, showed a reduced visual brain infarct size. As such, this demonstrates a therapeutic effect on ischemic brain injury caused by occlusion, however it is important to note that a pharmacological effect cannot be concluded by this study. Ultimately, our study suggests that the excipient inhibitor-based microemulsion formulation could be a promising concept for the substrate drugs of CYP3A.
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http://dx.doi.org/10.3390/pharmaceutics12080737 | DOI Listing |
Chem Biodivers
September 2025
School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products/College of Modern Biomedical Industry, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, P. R. China.
20(R)-ginsenoside Rg3 can reduce the effects of oxidative stress and cell death in cerebral ischemia‒reperfusion injury (CIRI). Neuroinflammation is crucial post-CIRI, but how 20(R)-Rg3 affects ischemia‒reperfusion-induced neuroinflammation is unclear. To study 20(R)-Rg3's effects on neuroinflammation and neuronal preservation in stroke models and explore toll-like receptor 4/myeloid differentiation factor-88/nuclear factor kappa B (TLR4/MyD88/NF-κB) pathway mechanisms.
View Article and Find Full Text PDFClin Transplant
September 2025
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Background: Liver transplantation is the definitive treatment for end-stage liver disease and some cancers. The use of livers from donors following pre-donation cardiac arrest (PDCA), especially with prolonged downtime duration, has been limited outside of the US due to fears over inferior outcomes from ischemic injury. However, PDCA may induce ischemic preconditioning, paradoxically improving post-transplant outcomes.
View Article and Find Full Text PDFCNS Drugs
September 2025
Global Health Neurology Lab, Sydney, NSW, 2150, Australia.
Acute ischemic stroke (AIS) remains a leading cause of mortality and long-term disability globally, with survivors at high risk of recurrent stroke, cardiovascular events, and post-stroke dementia. Statins, while widely used for their lipid-lowering effects, also possess pleiotropic properties, including anti-inflammatory, endothelial-stabilizing, and neuroprotective actions, which may offer added benefit in AIS management. This article synthesizes emerging evidence on statins' dual mechanisms of action and evaluates their role in reducing recurrence, improving survival, and mitigating cognitive decline.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
Brain Behav
September 2025
Department of Thoracic Surgery II, Department of Lung Transplantation, Organ Transplantation Center, the First Hospital of Jilin University, Changchun, China.
Background: Ischemic stroke (IS) treatment remains a significant challenge. This study aimed to identify potential druggable genes for IS using a systematic druggable genome-wide Mendelian Randomization (MR) analysis.
Methods: Two-sample MR analysis was conducted to identify the causal association between potential druggable genes and IS.