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Lipid-Encapsuled Grape Tannins Prevent Oxidative-Stress-Induced Neuronal Cell Death, Intracellular ROS Accumulation
Hugo S Díaz1, Angélica Ríos-Gallardo1, Domiziana Ortolani1
1Laboratory of Cardiorespiratory Control, Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile.
Abstract:
The central nervous system (CNS) is particularly vulnerable to oxidative stress and inflammation, which affect neuronal function and survival. Nowadays, there is great interest in the development of antioxidant and anti-inflammatory compounds extracted from natural products, as potential strategies to reduce the oxidative/inflammatory environment within the CNS and then preserve neuronal integrity and brain function. However, an important limitation of natural antioxidant formulations (mainly polyphenols) is their reduced in vivo bioavailability. The biological compatible delivery system containing polyphenols may serve as a novel compound for these antioxidant formulations. Accordingly, in the present study, we used liposomes as carriers for grape tannins, and we tested their ability to prevent neuronal oxidative stress and inflammation. Cultured catecholaminergic neurons (CAD) were used to establish the potential of lipid-encapsulated grape tannins (TLS) to prevent neuronal oxidative stress and inflammation following an oxidative insult. TLS rescued cell survival after H2O2 treatment (59.4 ± 8.8% vs. 90.4 ± 5.6% H2O2 vs. TLS+ H2O2; p < 0.05) and reduced intracellular ROS levels by ~38% (p < 0.05), despite displaying negligible antioxidant activity in solution. Additionally, TLS treatment dramatically reduced proinflammatory cytokines’ mRNA expression after H2O2 treatment (TNF-α: 400.3 ± 1.7 vs. 7.9 ± 1.9-fold; IL-1β: 423.4 ± 1.3 vs. 12.7 ± 2.6-fold; p < 0.05; H2O2 vs. TLS+ H2O2, respectively), without affecting pro/antioxidant biomarker expression, suggesting that liposomes efficiently delivered tannins inside neurons and promoted cell survival. In conclusion, we propose that lipid-encapsulated grape tannins could be an efficient tool to promote antioxidant/inflammatory cell defense.
Insights
Lipid-encapsulated grape tannins (TLS) protect brain cells from oxidative stress and inflammation. This novel delivery system enhances the bioavailability of natural antioxidants, preserving neuronal integrity and brain function.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- The central nervous system (CNS) is susceptible to oxidative stress and inflammation, impacting neuronal health.
- Natural antioxidants, like polyphenols, show promise for neuroprotection but suffer from poor bioavailability.
- Liposomes offer a potential solution for delivering active compounds to the CNS.
Purpose of the Study:
- To investigate the neuroprotective effects of lipid-encapsulated grape tannins (TLS).
- To assess the ability of liposomes to enhance the delivery and efficacy of grape tannins in preventing neuronal damage.
Main Methods:
- Cultured catecholaminergic neurons (CAD) were exposed to an oxidative insult (H2O2).
- The effects of lipid-encapsulated grape tannins (TLS) on cell survival, reactive oxygen species (ROS) levels, and inflammatory cytokine expression were evaluated.
- Antioxidant activity in solution and intracellular ROS levels were measured.
Main Results:
- TLS significantly improved cell survival following H2O2 treatment.
- TLS reduced intracellular ROS levels by approximately 38%, demonstrating enhanced antioxidant capacity within neurons.
- TLS treatment markedly decreased the expression of pro-inflammatory cytokines (TNF-α and IL-1β) without altering pro/antioxidant biomarkers.
Conclusions:
- Lipid-encapsulation effectively delivered grape tannins into neurons, enhancing their antioxidant and anti-inflammatory actions.
- Lipid-encapsulated grape tannins represent a promising strategy for neuroprotection against oxidative stress and inflammation.
- This approach holds potential for developing novel therapeutic formulations for CNS disorders.

