3g-borneol co-loaded liposomes (3g-BO-Lips) demonstrated brain-specific targeting, reduced infarct volume, suppressed inflammatory responses, and restored behavioral and cognitive abilities in MCAO/R mice, indicating significant therapeutic efficacy in cerebral ischemia treatment.
Key Findings
Results
Compound 3g (5-hydroxy-1H-pyrazole-3-carboxylic acid) demonstrated excellent radical scavenging ability, neuroprotective effects, and Fe3+ chelating properties in OGD/R-induced cell models.
Compound 3g was identified from a series of 5-hydroxy-1H-pyrazole-3-carboxylic acid compounds for its radical scavenging ability
The compound showed neuroprotective effects in the oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cell model
Compound 3g also demonstrated chelating effect on Fe3+, which is relevant to iron-mediated oxidative stress in ischemic stroke
Methods
3g-BO-Lips (borneol co-loaded liposomes with compound 3g) were successfully prepared using the solvent injection method to improve BBB permeability.
The liposomes were prepared using the solvent injection method
Borneol was co-loaded with compound 3g to enhance blood-brain barrier (BBB) permeability
The formulation was designed to overcome the limited BBB penetration of compound 3g alone
Results
3g-BO-Lips reduced OGD/R-induced reactive oxygen species (ROS) levels in SH-SY5Y cells and restored mitochondrial membrane potential.
ROS reduction was demonstrated in SH-SY5Y neuroblastoma cells subjected to OGD/R conditions
The formulation restored mitochondrial membrane potential, indicating protection of mitochondrial function
These effects suggest cytoprotective mechanisms relevant to ischemia-reperfusion injury
Results
Imaging experiments confirmed that 3g-BO-Lips possessed brain-specific properties and could accumulate in the ischemic area in MCAO/R mice.
Brain-specific accumulation was confirmed using imaging experiments in vivo
The liposomes accumulated specifically in the ischemic area in the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model
The brain-targeting property was attributed to the borneol component facilitating BBB penetration
Results
In vivo pharmacodynamic studies showed that 3g-BO-Lips significantly reduced infarct volume in MCAO/R mice.
Infarct volume reduction was demonstrated in the MCAO/R mouse model of ischemic stroke
The reduction in infarct volume indicates neuroprotection at the tissue level in vivo
This finding was part of a broader pharmacodynamic assessment in the MCAO/R model
Results
3g-BO-Lips suppressed inflammatory responses in MCAO/R mice.
Anti-inflammatory effects were observed in the MCAO/R mouse model
Suppression of inflammatory responses is a key therapeutic mechanism relevant to ischemic stroke pathophysiology
This finding suggests the formulation addresses neuroinflammation as a component of its therapeutic effect
Results
3g-BO-Lips restored behavioral and cognitive abilities in MCAO/R mice.
Behavioral recovery was demonstrated in MCAO/R mice treated with 3g-BO-Lips
Cognitive abilities were also restored, indicating functional neuroprotection beyond tissue-level effects
These functional outcomes were assessed as part of in vivo pharmacodynamic studies in the MCAO/R model
What This Means
This research suggests that a new drug delivery system combining a novel antioxidant compound (called compound 3g) with borneol—a natural substance known to help drugs cross into the brain—inside tiny fat-based capsules called liposomes may offer a promising treatment approach for ischemic stroke. The researchers found that compound 3g on its own could neutralize harmful free radicals, protect nerve cells, and bind to iron (which contributes to brain damage after stroke) in laboratory cell models. However, to get this compound into the brain more effectively, they packaged it with borneol in liposomes, which improved its ability to cross the blood-brain barrier, the protective barrier that normally limits what can enter the brain.
In both cell-based and animal experiments, the combined liposome formulation (3g-BO-Lips) reduced harmful reactive oxygen species in nerve cells, protected mitochondria (the energy-producing structures in cells), and specifically accumulated in the damaged brain region after stroke in mice. In living mice with experimentally induced stroke, treatment with 3g-BO-Lips led to smaller areas of brain damage, reduced inflammation in the brain, and recovery of movement and cognitive function compared to untreated animals.
This research suggests that combining a targeted drug delivery vehicle with an antioxidant and neuroprotective agent may help address multiple aspects of stroke-related brain injury simultaneously—oxidative stress, inflammation, and cell death. The brain-specific targeting capability of the formulation is particularly notable, as getting therapeutic agents to the right location in the brain remains one of the major challenges in stroke treatment development.
Wu Y, Li S, Xiao R, Sheng M, Zhu P, Wang Q, et al.. (2026). Borneol-loaded liposomes modified with 5-hydroxy-1H-pyrazole-3-carboxylic acid enhance neuroprotection and brain specific for ischemic stroke therapy.. Bioorganic & medicinal chemistry. https://doi.org/10.1016/j.bmc.2026.118706