Anti-inflammatory activities of spilanthol-rich essential oil from Acmella oleracea and its nanoemulsion in the prevention of neurodegenerative disorders

Neurodegenerative diseases are a health problem that is growing more and more worldwide. As these pathologies mainly affect the elderly, their incidence is closely related to the increase in the average life span of the population. These pathologies are characterized by a multifactorial etiology involving common triggering causes like excitotoxicity, mitochondrial disfunction, accumulation of misfolded proteins, oxidative stress and inflammation. Among these, the neuroinflammatory process is emergeing as a key factor in the genesis of these pathologies. Microglia, through the production of pro-inflammatory and anti-inflammatory mediators, is essential in maintaining tissue homeostasis and physiological brain development. However, excessive microglial cells activation produces a large number of cytokines and reactive oxygen species (ROS) causing progressive neuronal loss[1]. Therefore, the modulation of pro- inflammatory molecules from microglia could be a promising strategy to counteract neurodegeneration. Acmella oleracea (L.), a medicinal plant native to Brazil, is known and exploited worldwide in traditional medicine for its pharmacological properties, which seem mainly related to its main secondary metabolite, the alkylamide spilanthol. Spilanthol showed various biological properties such as antimicrobial, diuretic, hepatoprotective, insecticidal, antinociceptive, analgesic, anti-inflammatory and antioxidant activities[2]. The aim of this study was to investigate the anti-inflammatory properties of a spilanthol-rich essential oil obtained with a microwave-assisted extraction method on A. oleracea aerial parts (AO) in BV-2 microglial cells. Cells were treated with different concentrations of AO, pure spilanthol (S) or a nanoemulsion (NE) containing AO for 24 h and then activated by to LPS (100 ng/mL). Cell viability, measured by MTT assay, was significantly increased by all treatments with respect to cells only exposed to LPS. Of note, AO and NE also decreased ROS levels measured by DCFH-DA assay, while S had no effect on this parameter. To better characterize the anti-inflammatory activity of AO, the expression of inflammatory mediators such as IL-1b, TNF-, COX-2 and iNOS was investigated by RT-PCR. Interestingly, all the treatments were able to reduce the LPS-induced up-regulation of these inflammatory mediators. These results suggest that AO potentially could be used as therapeutic agent in neurodegenerative diseases due to its antioxidant and anti-inflammatory properties. This work also evidences a promising application of NE as a new technological formulation to further increase the bioavailability of this essential oil.