Encapsulation of Olive Leaf Polyphenol-Rich Extract in Polymeric Micelles to Improve Its Intestinal Permeability.

In the present study, polymeric micelles were developed to improve the intestinal permeability of an extract of Olea europaea L. leaf with a high content of total polyphenols (49% w/w), with 41% w/w corresponding to the oleuropein amount. A pre-formulation study was conducted to obtain a stable formulation with a high loading capacity for extract. The freeze-drying process was considered to improve the stability of the formulation during storage. Micelles were characterized in terms of physical and chemical properties, encapsulation efficiency, stability, and in vitro release. The optimized system consisted of 15 mg/mL of extract, 20 mg/mL of Pluronic L121, 20 mg/mL of Pluronic F68, and 10 mg/mL of D-α-tocopheryl polyethylene glycol succinate (TPGS), with dimensions of 14.21 ± 0.14 nm, a polydisersity index (PdI) of 0.19 ± 0.05 and an encapsulation efficiency of 66.21 ± 1.11%. The influence of the micelles on polyphenol permeability was evaluated using both Parallel Artificial Membrane Permeability Assay (PAMPA) and the Caco-2 cell monolayer. In both assays, the polymeric micelles improved the permeation of polyphenols, as demonstrated by the increase in Pe and Papp values.

The Protective Role of Oleuropein Aglycone against Pesticide-Induced Toxicity in a Human Keratinocytes Cell Model.

The extensive use of agricultural pesticides to improve crop quality and yield significantly increased the risk to the public of exposure to small but repeated doses of pesticides over time through various routes, including skin, by increasing the risk of disease outbreaks. Although much work was conducted to reduce the use of pesticides in agriculture, little attention was paid to prevention, which could reduce the toxicity of pesticide exposure by reducing its impact on human health. Extra virgin olive oil (EVOO), a major component of the Mediterranean diet, exerts numerous health-promoting properties, many of which are attributed to oleuropein aglycone (OleA), the deglycosylated form of oleuropein, which is the main polyphenolic component of EVOO. In this work, three pesticides with different physicochemical and biological properties, namely oxadiazon (OXA), imidacloprid (IMID), and glyphosate (GLYPHO), were compared in terms of metabolic activity, mitochondrial function and epigenetic modulation in an in vitro cellular model of human HaCaT keratinocytes to mimic the pathway of dermal exposure. The potential protective effect of OleA against pesticide-induced cellular toxicity was then evaluated in a cell pre-treatment condition. This study showed that sub-lethal doses of OXA and IMID reduced the metabolic activity and mitochondrial functionality of HaCaT cells by inducing oxidative stress and altering intracellular calcium flux and caused epigenetic modification by reducing histone acetylation H3 and H4. GLYPHO, on the other hand, showed no evidence of cellular toxicity at the doses tested. Pretreatment of cells with OleA was able to protect cells from the damaging effects of the pesticides OXA and IMID by maintaining metabolic activity and mitochondrial function at a controlled level and preventing acetylation reduction, particularly of histone H3. In conclusion, the bioactive properties of OleA reported here could be of great pharmaceutical and health interest, as they could be further studied to design new formulations for the prevention of toxicity from exposure to pesticide use.

Pentacyclic Triterpenes from Olive Leaves Formulated in Microemulsion: Characterization and Role in De Novo Lipogenesis in HepG2 Cells.

Olea europaea L. leaves contain a wide variety of pentacyclic triterpenes (TTPs). TTPs exhibit many pharmacological activities, including antihyperlipidemic effects. Metabolic alterations, such as dyslipidemia, are an established risk factor for hepatocellular carcinoma (HCC). Therefore, the use of TTPs in the adjunctive treatment of HCC has been proposed as a possible method for the management of HCC. However, TTPs are characterized by poor water solubility, permeability, and bioavailability. In this work, a microemulsion (ME) loading a TTP-enriched extract (EXT) was developed, to overcome these limits and obtain a formulation for oral administration. The extract-loaded microemulsion (ME-EXT) was fully characterized, assessing its chemical and physical parameters and release characteristics, and the stability was evaluated for two months of storage at 4 °C and 25 °C. PAMPA (parallel artificial membrane permeability assay) was used to evaluate the influence of the formulation on the intestinal passive permeability of the TTPs across an artificial membrane. Furthermore, human hepatocarcinoma (HepG2) cells were used as a cellular model to evaluate the effect of EXT and ME-EXT on de novo lipogenesis induced by elevated glucose levels. The effect was evaluated by detecting fatty acid synthase expression levels and intracellular lipid accumulation. ME-EXT resulted as homogeneous dispersed-phase droplets, with significantly increased EXT aqueous solubility. Physical and chemical analyses showed the high stability of the formulation over 2 months. The formulation realized a prolonged release of TTPs, and permeation studies demonstrated that the formulation improved their passive permeability. Furthermore, the EXT reduced the lipid accumulation in HepG2 cells by inhibiting de novo lipogenesis, and the ME-EXT formulation enhanced the inhibitory activity of EXT on intracellular lipid accumulation.

EVOO Polyphenols Exert Anti-Inflammatory Effects on the Microglia Cell through TREM2 Signaling Pathway.

In Alzheimer's disease (AD), microglia, brain resident immune cells, become chronically inflammatory and neurotoxic. In recent years, neuroinflammation has attracted particular interest in the scientific community. The genetic variants of molecules associated with ''microgliopathies'', including the triggering receptor expressed in myeloid cells-2 (TREM2), result in increased risk of developing AD and cognitive decline. We performed a set of in vitro assays using human neuronal (SH-SY5Y) and microglial (BV2 and C13NJ) cell models. Cells were differentially treated with extra virgin olive oil (EVOO) polyphenols, oleuropein aglycone (OleA) and hydroxytyrosol (HT) before adding LPS. We evaluated the protective effects of these EVOO products by a set of biochemical and cell biology assays, including ELISA, MTT, ROS detection, Western blotting and immunofluorescence. Our results provide an integrated understanding of the neuroprotection exerted by polyphenols in terms of: (i) reduction of pro-inflammatory cytokines release (IL-6, IL-8, IP-10 and RANTES); (ii) activation of the TREM2-dependent anti-inflammatory pathway; (iii) enhancement of protective microglial activity favoring the M2 polarization phenotype. Such findings provide new and important insights into the mechanisms by which the dietary olive polyphenols exert beneficial properties against neuroinflammation and neuronal impairment.

Ameliorative Effect of Posidonia oceanica on High Glucose-Related Stress in Human Hepatoma HepG2 Cells.

Metabolic disorders characterized by elevated blood glucose levels are a recognized risk factor for hepatocellular carcinoma (HCC). Lipid dysregulation is critically involved in the HCC progression, regulating energy storage, metabolism, and cell signaling. There is a clear link between de novo lipogenesis in the liver and activation of the NF-κB pathway, which is involved in cancer metastasis via regulation of metalloproteinases MMP-2/9. As conventional therapies for HCC reach their limits, new effective and safe drugs need to be found for the prevention and/or adjuvant therapy of HCC. The marine plant Posidonia oceanica (L.) Delile is endemic to the Mediterranean and has traditionally been used to treat diabetes and other health disorders. The phenol-rich leaf extract of Posidonia oceanica (POE) is known to have cell-safe bioactivities. Here, high glucose (HG) conditions were used to study lipid accumulation and fatty acid synthase (FASN) expression in human HepG2 hepatoma cells using Oil Red O and Western blot assays. Under HG conditions, the activation status of MAPKs/NF-κB axis and MMP-2/9 activity were determined by Western blot and gelatin zymography assays. The potential ameliorative role of POE against HG-related stress in HepG2 cells was then investigated. POE reduced lipid accumulation and FASN expression with an impact on de novo lipogenesis. Moreover, POE inhibited the MAPKs/NF-κB axis and, consequently, MMP-2/9 activity. Overall, these results suggest that P. oceanica may be a potential weapon in the HCC additional treatment.

Posidonia oceanica (L.) (Delile, 1813) extracts as a potential booster biocide in fouling-release coatings.

Since the banning of tributyltin, the addition of inorganic (metal oxides) and organic (pesticides, herbicides) biocides in antifouling paint has represented an unavoidable step to counteract biofouling and the resulting biodeterioration of submerged surfaces. Therefore, the development of new methods that balance antifouling efficacy with environmental impact has become a topic of great importance. Among several proposed strategies, natural extracts may represent one of the most suitable alternatives to the widely used toxic biocides. Posidonia oceanica is one of the most representative organisms of the Mediterranean Sea and contains hundreds of bioactive compounds. In this study, we prepared, characterized, and assessed a hydroalcoholic extract of P. oceanica and then compared it to three model species. Together, these four species belong to relevant groups of biofoulers: bacteria (Aliivibrio fischeri), diatoms (Phaeodactylum tricornutum), and serpulid polychaetes (Ficopomatus enigmaticus). We also added the same P. oceanica extract to a PDMS-based coating formula. We tested this coating agent with Navicula salinicola and Ficopomatus enigmaticus to evaluate both its biocidal performance and its antifouling properties. Our results indicate that our P. oceanica extract provides suitable levels of protection against all the tested organisms and significantly reduces adhesion of N. salinicola cells and facilitates their release in low-intensity waterflows.

Usnic Acid-Loaded Polymeric Micelles: An Optimal Migrastatic-Acting Formulation in Human SH-SY5Y Neuroblastoma Cells.

Usnic acid (UA) is one of the most abundant and common metabolites of lichens, known for its numerous pharmacological properties. Nevertheless, it presents some criticalities that severely limit its use in therapy: poor solubility in water and significant hepatotoxicity. Soluplus and Solutol HS15 and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) were employed to develop polymeric micelles (UA-PM). The chemical and physical properties of the system were characterized, including the size, homogeneity, zeta potential, critical micellar concentration (CMC), encapsulation efficiency (EE%), and in vitro release. The freeze-drying process was considered to prevent agglomeration and improve the stability of the formulation. The stability of the micelles and the freeze-dried product (UA-PML) was also evaluated. The anti-migratory activity of UA and UA-PM was evaluated in human neuroblastoma SH-SY5Y cells using the wound healing assay. Their effect on the activity of metalloproteinases (MMP)-2/9 involved in the migration process of cells was verified by gelatin zymography. The optimized UA-PM contained Soluplus, Solutol HS15, and TPGS in a 1:4:0.5 weight ratio and increased the aqueous solubility to about 150-fold solubilized, solubilizing 0.5 mg/mL of UA. UA-PM has a small size (45.39 ± 0.31 nm), a polydispersity index (PDI) of 0.26 ± 0.01, and an EE% of 82.13 ± 5.57%. The colloidal dispersion was stable only for 9 days at 4 °C, while the freeze-drying process improved the stability for up to 30 days. UA was released for a prolonged period during the in vitro release study. The in vitro cell-based experiments showed that UA-PM (0.2 µg/mL) inhibited SH-SY5Y cell migration and the gelatinolytic activity of MMP-2/9 in culture media, while free UA at the same concentration exerted no biological activity. This study demonstrates that polymeric micelles are an excellent formulation for UA to manifest inhibitory action on neuroblastoma cell migration.

Microemulsions Enhance the In Vitro Antioxidant Activity of Oleanolic Acid in RAW 264.7 Cells.

Oleanolic acid (OA) is the main triterpenic acid of olive leaves known for numerous pharmacological properties, including antioxidant activity. However, it is poorly soluble in water and consequently with low bioavailability, which limits its pharmacological application. Microemulsions (MEs) are dispersed systems consisting of two immiscible phases that promote rapid solubilization and absorption in the gastrointestinal tract. To improve both solubility and intestinal permeability of this molecule, OA has been formulated in two different microemulsions (ME-1 and ME-2). A solubility screening was carried out to select the ME components, and pseudoternary phase diagrams were constructed to evaluate the region of existence and select the appropriate amount of the constituents. ME-1 was prepared using Capmul PG-8/NF as the oily phase, and Transcutol and Tween 20 (7:3) as surfactants, while ME-2 contained Nigella oil and Isopropil myristate as the oily phase, and Transcutol HP and Cremophor EL (2:1) as surfactants. The OA solubility was increased by 1000-fold and 3000-fold in ME-1-OA and ME-2-OA, respectively. The MEs' droplet size and the PdI were evaluated, and the stability was assessed for 8 weeks by monitoring chemical and physical parameters. The parallel artificial membrane permeability assay (PAMPA) also demonstrated an enhanced intestinal permeability of both OA formulations compared with free OA. The potential ability of both MEs to enhance the bioactivity of OA against LPS-induced oxidative stress in RAW 264.7 murine macrophages was also investigated. Overall, this study suggests that both MEs promote a bio-enhancement of the protective action of OA against the LPS-induced pro-oxidant stress in macrophages. Overall, this study suggests that MEs could be an interesting formulation to improve OA oral bioavailability with potential clinical applications.

Neutrophil Gelatinase-Associated Lipocalin as Potential Predictive Biomarker of Melanoma and Non-Melanoma Skin Cancers in Psoriatic Patients: A Pilot Study.

Background: Studies have demonstrated a higher risk of nonmelanoma skin cancers (NMSC) and a modestly increased melanoma risk in patients with psoriasis. To date, no biomarkers predictive of evolution have been identified yet. Methods: The aim of this prospective case-control study was to investigate the potential role of neutrophil gelatinase-associated lipocalin (NGAL) as a predictive biomarker of skin cancers in psoriatic patients. Patients with a diagnosis of psoriasis were enrolled, as well as healthy subjects and patients with skin cancers as controls. Plasma protein expression of NGAL, metalloproteinases (MMP)-2, and MMP-9 was performed by an enzyme-linked immunosorbent assay (ELISA). In all the patients who developed skin cancer at follow-up, NGAL, MMP-2, and MMP-9 serum levels were dosed again. Results: Plasma NGAL levels were significantly higher in psoriatic patients with NMSC than without (182.3 ± 36.6 ng/mL vs. 139.9 ± 39.3 ng/mL) (p < 0.001). Plasma NGAL levels were significantly higher (p < 0.00001) in patients with psoriasis and NMSC than in patients with skin tumors without psoriasis (182.3 vs. 122.9). Patients with psoriasis who developed NMSC at follow-up showed increased plasma MMP-9 levels. Conclusion: NGAL seems to play a role in the pathogenesis of NMSC but not melanoma in patients with psoriasis.

Significance of Serum Oxidative and Antioxidative Status in Congenital Central Hypoventilation Syndrome (CCHS) Patients.

Congenital central hypoventilation syndrome (CCHS) is a rare neurological genetic disorder that affects sleep-related respiratory control. Currently, no drug therapy is available. In light of this, there is a need for lifelong ventilation support, at least during sleep, for these patients. The pathogenesis of several chronic diseases is influenced by oxidative stress. Thus, determining oxidative stress in CCHS may indicate further disorders in the course of this rare genetic disease. Liquid biopsies are widely used to assess circulating biomarkers of oxidative stress. In this study, ferric reducing ability of plasma, thiobarbituric acid-reactive substances, advanced oxidation protein products (AOPPs), and advanced glycation end-products were measured in the serum of CCHS patients to investigate the relationship between oxidative stress and CCHS and the significance of this balance in CCHS. Here, AOPPs were found to be the most relevant serum biomarker to monitor oxidative stress in CCHS patients. According to this communication, CCHS patients may suffer from other chronic pathophysiological processes because of the persistent levels of AOPPs.

Glucose Uptake and Oxidative Stress in Caco-2 Cells: Health Benefits from Posidonia oceanica (L.) Delile.

Posidonia oceanica (L.) Delile is an endemic Mediterranean marine plant of extreme ecological importance. Previous in vitro and in vivo studies have demonstrated the potential antidiabetic properties of P. oceanica leaf extract. Intestinal glucose transporters play a key role in glucose homeostasis and represent novel targets for the management of diabetes. In this study, the ability of a hydroalcoholic P. oceanica leaf extract (POE) to modulate intestinal glucose transporters was investigated using Caco-2 cells as a model of an intestinal barrier. The incubation of cells with POE significantly decreased glucose uptake by decreasing the GLUT2 glucose transporter levels. Moreover, POE had a positive effect on the barrier integrity by increasing the Zonulin-1 levels. A protective effect exerted by POE against oxidative stress induced by chronic exposure to high glucose concentrations or tert-butyl hydroperoxide was also demonstrated. This study highlights for the first time the effect of POE on glucose transport, intestinal barrier integrity, and its protective antioxidant effect in Caco-2 cells. These findings suggest that the P. oceanica phytocomplex may have a positive impact by preventing the intestinal cell dysfunction involved in the development of inflammation-related disease associated with oxidative stress.

Urinary Biomarkers as a Proxy for Congenital Central Hypoventilation Syndrome Patient Follow-Up.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare genetic disorder of the autonomic nervous system and in particular of the respiratory control during sleep. No drug therapy is, to date, available; therefore, the survival of these patients depends on lifelong ventilatory support during sleep. Reactive oxygen species (ROS)-induced oxidative stress is a recognized risk factor involved in the pathogenesis of several chronic diseases. Therefore, monitoring systemic oxidative stress could provide important insights into CCHS outcomes. Because ROS-induced oxidative products are excreted as stable metabolites in urine, we performed an HPLC-MS/MS analysis for the quantitative determination of the three main representative oxidative biomarkers (i.e., diY, MDA, and 8-OHdG) in the urine of CCHS patients. Higher levels of urinary MDA were found in CCHS patients compared with age-matched control subjects. The noteworthy finding is the identification of urinary MDA as relevant biomarker of systemic oxidative status in CCHS patients. This study is a concise and smart communication about the impact that oxidative stress has in CCHS, and suggests the monitoring of urinary MDA levels as a useful tool for the management of these patients.

Marine Migrastatics: A Comprehensive 2022 Update.

Metastasis is responsible for the bad prognosis in cancer patients. Advances in research on metastasis prevention focus attention on the molecular mechanisms underlying cancer cell motility and invasion to improve therapies for long-term survival in cancer patients. The so-called "migrastatics" could help block cancer cell invasion and lead to the rapid development of antimetastatic therapies, improving conventional cancer therapies. In the relentless search for migrastatics, the marine environment represents an important source of natural compounds due to its enormous biodiversity. Thus, this review is a selection of scientific research that has pointed out in a broad spectrum of in vitro and in vivo models the anti-cancer power of marine-derived products against cancer cell migration and invasion over the past five years. Overall, this review might provide a useful up-to-date guide about marine-derived compounds with potential interest for pharmaceutical and scientific research on antimetastatic drug endpoints.

Dihydroauroglaucin Isolated from the Mediterranean Sponge Grantia compressa Endophyte Marine Fungus Eurotium chevalieri Inhibits Migration of Human Neuroblastoma Cells.

Cancer cell migration is a hallmark of the aggressiveness and progression of malignancies such as high-risk neuroblastoma. Given the lack of effective therapeutic solutions to counteract cancer progression, basic research aims to identify novel bioactive molecules with inhibitory potential on cancer cell migration. In this context, this work investigated the role of members of the salicylaldehyde secondary metabolite set from the sponge endophyte fungus Eurotium chevalieri MUT 2316 as potential inhibitors of human neuroblastoma SH-SY5Y cell migration. Since tetrahydroauroglaucin (TAG) and dihydroauroglaucin (DAG) were isolated in large amounts, both were evaluated for their anticancer properties towards SH-SY5Y cells. Both molecules were found to be non-cytotoxic by MTT assay and cytofluorimetric analysis. Moreover, DAG showed efficacy in inhibiting the highly migratory phenotype of SH-SY5Y cells by wound healing assay; whereas TAG, although structurally similar to DAG, showed no anti-migratory effect. Therefore, this work provides good reasons to conduct further in vitro and in vivo studies focusing on DAG as a potentially useful migrastatic natural marine molecule.

Antioxidant and Anti-Inflammatory Agents from the Sea: A Molecular Treasure for New Potential Drugs.

Nowadays, natural compounds are widely used worldwide for the treatment of human diseases and health disorders [...].

News and Updates from 2022 on Antioxidant and Anti-Inflammatory Properties of Marine Products.

Inflammation and oxidative stress are often the common denominators of most modern chronic diseases and disorders, resulting in serious problems for health care systems [...].

Posidonia oceanica (L.) Delile Extract Reduces Lipid Accumulation through Autophagy Activation in HepG2 Cells.

Posidonia oceanica (L.) Delile is a marine plant traditionally used as an herbal medicine for various health disorders. P. oceanica leaf extract (POE) has been shown to be a phytocomplex with cell-safe bioactivities, including the ability to trigger autophagy. Autophagy is a key pathway to counteract non-alcoholic fatty liver disease (NAFLD) by controlling the breakdown of lipid droplets in the liver. The aim of this study was to explore the ability of POE to trigger autophagy and reduce lipid accumulation in human hepatoma (HepG2) cells and then verify the possible link between the effect of POE on lipid reduction and autophagy activation. Expression levels of autophagy markers were monitored by the Western blot technique in POE-treated HepG2 cells, whereas the extent of lipid accumulation in HepG2 cells was assessed by Oil red O staining. Chloroquine (CQ), an autophagy inhibitor, was used to study the relationship between POE-induced autophagy and intracellular lipid accumulation. POE was found to stimulate an autophagy flux over time in HepG2 cells by lowering the phosphorylation state of ribosomal protein S6, increasing Beclin-1 and LC3-II levels, and decreasing p62 levels. By blocking autophagy with CQ, the effect of POE on intracellular lipid accumulation was clearly reversed, suggesting that the POE phytocomplex may reduce lipid accumulation in HepG2 cells by activating the autophagic process. This work indicates that P. oceanica may be considered as a promising molecule supplier to discover new natural approaches for the management of NAFLD.

Posidonia oceanica (L.) Delile Dampens Cell Migration of Human Neuroblastoma Cells.

Neuroblastoma (NB) is a common cancer in childhood, and lethal in its high-risk form, primarily because of its high metastatic potential. Targeting cancer cell migration, and thus preventing metastasis formation, is the rationale for more effective cancer therapy against NB. Previous studies have described the leaf extract from Posidonia oceanica marine plant (POE) as an antioxidant, anti-inflammatory agent and inhibitor of cancer cell migration. This study aims to examine the POE anti-migratory role in human SH-SY5Y neuroblastoma cells and the underlying mechanisms of action. Wound healing and gelatin zymography assays showed that POE at early times inhibits cell migration and reduces pro-MMP-2 release into culture medium. By monitoring expression level of key autophagy markers by Western blot assay, a correlation between POE-induced cell migration inhibition and autophagy activation was demonstrated. Cell morphology and immunofluorescence analyses showed that POE induces neurite formation and neuronal differentiation at later times. These results suggest POE might act against cell migration by triggering early nontoxic autophagy. The POE-induced cellular morphological change toward cell differentiation might contribute to prolonging the phytocomplex anti-migratory effect to later times. Overall, these results encourage future in vivo studies to test POE applicability in neuroblastoma treatment.

An Overview of New Insights into the Benefits of the Seagrass Posidonia oceanica for Human Health.

Posidonia oceanica (L.) Delile is a Mediterranean-endemic angiosperm often described for its great ecological importance. Despite evidence of a millennia-old relationship between P. oceanica and humans, as well as traditional medicine applications, the potential benefits of P. oceanica for human health have been documented only recently. This review aims to compile newly acquired knowledge on P. oceanica bioactive properties that allow the scientific community to look at this plant as a promising source of natural therapeutical products for human health. Experimental investigations conducted in both in vitro cellular-based and in vivo animal models pave the way for new research projects aiming at the development of alternative and complementary therapeutic strategies based on P. oceanica against a wide range of pathological conditions.

Efficacy of Posidonia oceanica Extract against Inflammatory Pain: In Vivo Studies in Mice.

Posidonia oceanica (L.) Delile is traditionally used for its beneficial properties. Recently, promising antioxidant and anti-inflammatory biological properties emerged through studying the in vitro activity of the ethanolic leaves extract (POE). The present study aims to investigate the anti-inflammatory and analgesic role of POE in mice. Inflammatory pain was modeled in CD-1 mice by the intraplantar injection of carrageenan, interleukin IL-1ß and formalin. Pain threshold was measured by von Frey and paw pressure tests. Nociceptive pain was studied by the hot-plate test. POE (10-100 mg kg-1) was administered per os. The paw soft tissue of carrageenan-treated animals was analyzed to measure anti-inflammatory and antioxidant effects. POE exerted a dose-dependent, acute anti-inflammatory effect able to counteract carrageenan-induced pain and paw oedema. Similar anti-hyperalgesic and anti-allodynic results were obtained when inflammation was induced by IL-1ß. In the formalin test, the pre-treatment with POE significantly reduced the nocifensive behavior. Moreover, POE was able to evoke an analgesic effect in naïve animals. Ex vivo, POE reduced the myeloperoxidase activity as well as TNF-α and IL-1ß levels; further antioxidant properties were highlighted as a reduction in NO concentration. POE is the candidate for a new valid strategy against inflammation and pain.