The increase in life expectancy is leading to a consequent rise in the incidence of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, which mainly affect the elderly population. These conditions share several features, such as abnormal protein deposition, oxidative stress, impaired mitochondrial function, and neuroinflammation. The latter plays a crucial role in the pathogenesis of these diseases, and it involves the activation of microglia, the resident immune cells of the brain with an important role in maintaining CNS (central nervous system) homeostasis. In neurodegenerative diseases, microglia are excessively activated, leading to the overproduction of pro-inflammatory mediators such as cytokines, reactive oxygen species, and nitric oxide (NO), causing neuronal death. Extra virgin olive oil (EVOO) has been widely associated with beneficial properties, mainly attributed to its phenols, which exert antioxidant and anti-inflammatory activities. Among them, oleocanthal (OL) is known for its several demonstrated health benefits. Of note, it has a strong anti-inflammatory “ibuprofen-like” activity since it inhibits the cyclooxygenase enzymes. During olive oil shelf-life, phenolic compounds may be modified by different processes. In particular, OL is progressively oxidized to oleocanthalic acid (OA) and this conversion is accelerated by inappropriate storage conditions. To date, the biological effects of OA are completely unknown, and the anti-inflammatory activity of OL has not been characterized in the brain yet. On these bases, the aim of this study was to investigate the potential anti-inflammatory activity of OL and OA in an in vitro model of neuroinflammation. BV-2 microglial cells were treated with OL and OA at different concentrations and after 2 h activated with LPS 100 ng/ml for 24 h. NO production, analyzed with Griess assay, was significantly reduced by OL, but not by OA, compared to cells exposed only to LPS. Furthermore, OL significantly decreased the gene expression of pro-inflammatory factors, namely iNOS, NLRP3, COX2, IL-1β, IL-6 and TNF-α and up-regulated anti-inflammatory mediators such as IL-4 and CD206, compared to LPS. Conversely, OA significantly reduced only the expression of IL-1β and COX2, although to a lesser extent than OL. In addition, the protein levels of iNOS and NLRP3, analyzed by immunoblotting, were significantly reduced by OL compared to LPS, but not by OA. Interestingly, OL was able to completely inhibit p38 MAPK phosphorylation induced by LPS suggesting that the reduction of neuroinflammation triggered by OL could be, at least partially, due to the modulation of this signaling pathway. In conclusion, our data clearly demonstrate that OL exerts a strong anti-inflammatory activity in the brain, by efficiently counteracting microglia activation. This confirms the beneficial role of EVOO consumption for human health. Nonetheless, the strong biological activity of this compound is lost when it’s oxidized to OA. This emphasizes how crucial is to store EVOO in appropriate conditions and highlights the importance of consuming EVOO as fresh as possible to benefit from the health effects of this product.

Investigation of the anti-inflammatory activity of oleocanthal and oleocanthalic acid in an in vitro model of neuroinflammation

Rinaldi, Irene;Barbalace, Maria Cristina;Freschi, Michela;Malaguti, Marco;Angeloni, Cristina;Hrelia, Silvana
2023

Abstract

The increase in life expectancy is leading to a consequent rise in the incidence of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, which mainly affect the elderly population. These conditions share several features, such as abnormal protein deposition, oxidative stress, impaired mitochondrial function, and neuroinflammation. The latter plays a crucial role in the pathogenesis of these diseases, and it involves the activation of microglia, the resident immune cells of the brain with an important role in maintaining CNS (central nervous system) homeostasis. In neurodegenerative diseases, microglia are excessively activated, leading to the overproduction of pro-inflammatory mediators such as cytokines, reactive oxygen species, and nitric oxide (NO), causing neuronal death. Extra virgin olive oil (EVOO) has been widely associated with beneficial properties, mainly attributed to its phenols, which exert antioxidant and anti-inflammatory activities. Among them, oleocanthal (OL) is known for its several demonstrated health benefits. Of note, it has a strong anti-inflammatory “ibuprofen-like” activity since it inhibits the cyclooxygenase enzymes. During olive oil shelf-life, phenolic compounds may be modified by different processes. In particular, OL is progressively oxidized to oleocanthalic acid (OA) and this conversion is accelerated by inappropriate storage conditions. To date, the biological effects of OA are completely unknown, and the anti-inflammatory activity of OL has not been characterized in the brain yet. On these bases, the aim of this study was to investigate the potential anti-inflammatory activity of OL and OA in an in vitro model of neuroinflammation. BV-2 microglial cells were treated with OL and OA at different concentrations and after 2 h activated with LPS 100 ng/ml for 24 h. NO production, analyzed with Griess assay, was significantly reduced by OL, but not by OA, compared to cells exposed only to LPS. Furthermore, OL significantly decreased the gene expression of pro-inflammatory factors, namely iNOS, NLRP3, COX2, IL-1β, IL-6 and TNF-α and up-regulated anti-inflammatory mediators such as IL-4 and CD206, compared to LPS. Conversely, OA significantly reduced only the expression of IL-1β and COX2, although to a lesser extent than OL. In addition, the protein levels of iNOS and NLRP3, analyzed by immunoblotting, were significantly reduced by OL compared to LPS, but not by OA. Interestingly, OL was able to completely inhibit p38 MAPK phosphorylation induced by LPS suggesting that the reduction of neuroinflammation triggered by OL could be, at least partially, due to the modulation of this signaling pathway. In conclusion, our data clearly demonstrate that OL exerts a strong anti-inflammatory activity in the brain, by efficiently counteracting microglia activation. This confirms the beneficial role of EVOO consumption for human health. Nonetheless, the strong biological activity of this compound is lost when it’s oxidized to OA. This emphasizes how crucial is to store EVOO in appropriate conditions and highlights the importance of consuming EVOO as fresh as possible to benefit from the health effects of this product.
2023
1° Congresso intersocietà sui prodotti vegetali per la salute: il ruolo delle piante medicinali nella medicina moderna_PROGRAMMA
158
158
Rinaldi, Irene; Barbalace, Maria Cristina; Freschi, Michela; Malaguti, Marco; Digiacomo, Maria; Giusti, Laura; Lucacchini, Antonio; Angeloni, Cristina; Hrelia, Silvana
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/959652
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