Pterostilbene, a natural compound found abundantly in blueberries and grapes, has demonstrated significant protective effects against lipopolysaccharide (LPS)-induced inflammation and disruption of the blood-brain barrier (BBB), according to recent research from the University of Macau. This study, published in Scientific Reports, highlights the compound's potential as a therapeutic agent for preventing neuroinflammation and associated diseases.
The BBB serves as a selective barrier protecting the brain from harmful substances and regulating the influx of nutrients. Dysfunction of this barrier is linked to various neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The researchers set out to investigate how pterostilbene could mitigate the effects of LPS, a bacterial endotoxin known to incite inflammatory responses and disrupt BBB integrity.
The study revealed pterostilbene’s capacity to upregulate the expression of tight junction (TJ) proteins, ZO-1 and claudin-5, which are pivotal for maintaining the structure of the BBB. These proteins act as gatekeepers, ensuring proper permeability of the endothelial cell layer. Conversely, pterostilbene downregulated the expression of adhesion molecules (ICAM-1 and VCAM-1), which are markers of inflammation and are known to exacerbate BBB disruption when elevated.
Through various experimental methodologies, including cell viability assays and western blot analysis, the research team determined effective pterostilbene concentrations for protecting brain endothelial cells (bEnd.3) from LPS-induced damage. The findings indicated clear anti-inflammatory properties, with pterostilbene reducing levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α).
One of the more remarkable outcomes of this study is the identification of the underlying molecular pathways involved. Specifically, pterostilbene inhibited the activation of the nuclear factor kappa B (NF-κB) pathway and the mitogen-activated protein kinase (MAPK) pathway, both of which are critically involved in the regulation of inflammatory responses within the CNS. For example, inhibition of NF-κB prevented its translocation to the nucleus, which is necessary for the expression of pro-inflammatory genes.
“Pterostilbene effectively upregulated the expressions of tight junction (TJ) proteins such as zonula occludens (ZO)-1 and claudin-5,” the authors of the report stated. They explained how maintaining these tight junctions is key to preserving BBB integrity during inflammatory insults.
Beyond its anti-inflammatory actions, the study also noted the antioxidant effects of pterostilbene, as it activated heme oxygenase-1 (HO-1) and thereby reduced oxidative stress and reactive oxygen species (ROS) levels within the cells. This dual action—combination of anti-inflammatory and antioxidant effects—positions pterostilbene as a potentially powerful protector of neuronal health.
Research surrounding pterostilbene is gaining momentum, owing to its stronger bioavailability compared to resveratrol and its neuroprotective properties. Previous studies have suggested pterostilbene may also provide benefits for other conditions related to BBB dysfunction and neuroinflammation. Our study sheds light on new pathways through which pterostilbene can exert its beneficial effects on brain endothelial cells,” the researchers concluded, calling for continued exploration of its therapeutic potential.
Given the increase of conditions linked to BBB disruption, such as multiple sclerosis and neurodegenerative diseases, the findings of this research may not only inform future studies but could also lead to the development of novel treatments aimed at enhancing BBB function and protecting against inflammation-induced neuronal damage.