Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation.

Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration.

Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L.

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from 'Gorilla Glue' was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-κB pathway. Moreover, the sesquiterpenes (E)-caryophyllene, α-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils' anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of α-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation.

Out of Sight Out of Mind: Perceived Physical Distance Between the Observer and Someone in Pain Shapes Observer's Neural Empathic Reactions.

Social and affective relations may shape empathy to others' affective states. Previous studies also revealed that people tend to form very different mental representations of stimuli on the basis of their physical distance. In this regard, embodied cognition and embodied simulation propose that different physical distances between individuals activate different interpersonal processing modes, such that close physical distance tends to activate the interpersonal processing mode typical of socially and affectively close relationships. In Experiment 1, two groups of participants were administered a pain decision task involving upright and inverted face stimuli painfully or neutrally stimulated, and we monitored their neural empathic reactions by means of event-related potentials (ERPs) technique. Crucially, participants were presented with face stimuli of one of two possible sizes in order to manipulate retinal size and perceived physical distance, roughly corresponding to the close and far portions of social distance. ERPs modulations compatible with an empathic reaction were observed only for the group exposed to face stimuli appearing to be at a close social distance from the participants. This reaction was absent in the group exposed to smaller stimuli corresponding to face stimuli observed from a far social distance. In Experiment 2, one different group of participants was engaged in a match-to-sample task involving the two-size upright face stimuli of Experiment 1 to test whether the modulation of neural empathic reaction observed in Experiment 1 could be ascribable to differences in the ability to identify faces of the two different sizes. Results suggested that face stimuli of the two sizes could be equally identifiable. In line with the Construal Level and Embodied Simulation theoretical frameworks, we conclude that perceived physical distance may shape empathy as well as social and affective distance.