Redox Modulation of Meniere Disease by Coriolus Versicolor Treatment, a Nutritional Mushroom Approach with Neuroprotective Potential.

BACKGROUND: Meniere's disease (MD) is a cochlear neurodegenerative disease. Hearing loss appears to be triggered by oxidative stress in the ganglion neurons of the inner ear. OBJECTIVE: Here, we confirm the variation of markers of oxidative stress and inflammation in patients with Meniere and hypothesize that chronic treatment with Coriolus mushroom helps in the response to oxidative stress and acts on α-synuclein and on NF-kB-mediated inflammatory processes. METHODS: Markers of oxidative stress and inflammation were evaluated in MD patients with or without Coriolus treatment for 3 or 6 months. RESULTS: MD patients had a small increase in Nrf2, HO-1, γ-GC, Hsp70, Trx and sirtuin-1, which were further increased by Coriolus treatment, especially after 6 months. Increased markers of oxidative damage, such as protein carbonyls, HNE, and ultraweak chemiluminescence, associated with a decrease in plasma GSH/GSSG ratio, were also observed in lymphocytes from MD patients. These parameters were restored to values similar to the baseline in patients treated with Coriolus for both 3 and 6 months. Furthermore, treated MD subjects showed decreased expression of α-synuclein, GFAP and Iba-1 proteins and modulation of the NF-kB pathway, which were impaired in MD patients. These changes were greatest in subjects taking the supplements for 6 months. CONCLUSIONS: Our study suggests MD as a model of cochlear neurodegenerative disease for the identification of potent inducers of the Nrf2-vitagene pathway, able to reduce the deleterious consequences associated with neurodegenerative damage, probably by indirectly acting on α-synuclein expression and on inflammatory processes NF- kB-mediated.

Antioxidant Activity of a Sicilian Almond Skin Extract Using In Vitro and In Vivo Models.

Almond skins are known for their antioxidative and anti-inflammatory properties, which are mainly due to the presence of polyphenols. The aim of the present study was to evaluate the antioxidant and anti-inflammatory effects of almond skin extract (ASE) obtained from the Sicilian cultivar "Fascionello" and to evaluate the possible mechanisms of action using an in vitro model of human monocytic U937 cells as well as an in vivo model of carrageenan (CAR)-induced paw edema. The in vitro studies demonstrated that pretreatment with ASE inhibited the formation of ROS and apoptosis. The in vivo studies showed that ASE restored the CAR-induced tissue changes; restored the activity of endogenous antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione; and decreased neutrophil infiltration, lipid peroxidation, and the release of proinflammatory mediators. The anti-inflammatory and antioxidant effects of ASE could be associated with the inhibition of the pro-inflammatory nuclear NF-κB and the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) antioxidant pathways. In conclusion, almond skin could reduce the levels of inflammation and oxidative stress and could be beneficial in the treatment of several disorders.

Targeting Nrf2 and NF-κB Signaling Pathways in Inflammatory Pain: The Role of Polyphenols from Thinned Apples.

Diet can modulate the different stages of inflammation due to the presence of bioactive compounds such as polyphenols. Apples are a great source of phenolic compounds that show anti-inflammatory and antioxidant properties, and these might be used as a dietary supplement and/or functional element in the treatment of chronic inflammatory illnesses. The aim of our study was to evaluate the anti-inflammatory and antioxidant actions of thinned apple polyphenol (TAP) extracts in a model of paw edema. The experimental model was induced in rats via subplantar injections of 1% λ-Carrageenan (CAR) in the right hind leg, and TAP extract was administered via oral gavage 30 min before and 1 h after the CAR injection at doses of 5 mg/kg and 10 mg/kg, respectively. The inflammatory response is usually quantified by the increase in the size of the paw (edema), which is maximal about 5 h after the injection of CAR. CAR-induced inflammation generates the release of pro-inflammatory mediators and reactive oxygen species (ROS). Furthermore, the inflammatory state induces the pain that involves the peripheral nociceptors, but above all it acts centrally at the level of the spinal cord. Our results showed that the TAP extracts reduced paw histological changes, neutrophil infiltration, mast cell degranulation, and oxidative stress. Additionally, the oral administration of TAP extracts decreased thermal and mechanical hyperalgesia, along with a reduction in spinal microglia and the markers of nociception. In conclusion, we demonstrate that TAP extract is able to modulate inflammatory, oxidative, and painful processes, and is also useful in the treatment of the symptoms associated with paw edema.

Uroprotective and pain-relieving effect of dietary supplementation with micronized palmitoyl-glucosamine and hesperidin in a chronic model of cyclophosphamide-induced cystitis.

Introduction: Feline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations. Methods: The current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug. Results: Higher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson's trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine. Discussion: PGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.

Regulation of Apoptosis and Oxidative Stress by Oral Boswellia Serrata Gum Resin Extract in a Rat Model of Endometriosis.

Endometriosis (EMS) is a gynecological disease characterized by inflammation, oxidative stress, and apoptosis dysregulation. This study aims to evaluate the effect of Boswellia serrata gum resin extract (BS) on the endometriotic lesions in a rat model of endometriosis. We divided female rats into three groups, including Sham, EMS, EMS + BS. In the EMS and EMS + BS groups, pathology was induced and after 7 days by the abdominal high-frequency ultrasound (hfUS) analysis the presence of the endometriotic lesions was confirmed. Subsequently, the EMS + BS group was administered with BS (100 mg/Kg) daily for another 7 days. At the end of the experiment, the hfUS analysis was repeated and the animals were sacrificed to evaluate the size and histoarchitecture of the endometriotic implants. Pelvic ultrasound showed increased size of the endometriotic lesions in the Endo group, while BS administration reduced the lesion size. The macroscopic analysis confirmed the reduced area and volume of the endometriotic lesions of the EMS + BS group. The histological analysis showed reduced characteristic of ectopic stroma and glands in the animals treated with BS. Western blot analyses were conducted to evaluate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. BS increases the expression of Nfr2 in the nucleus and the expression of its downstream antioxidant proteins NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. BS administration also restored the impaired apoptotic pathway in the lesions by reducing Bcl-2 expression and increasing Bax and cleaved caspase 9 levels. The BS apoptotic effect was also confirmed by the cleavage of PARP, another specific marker of apoptosis, and by the TUNEL assay. Our results show that BS administration resulted in an effective and coordinated suppression of Endo owing to its antioxidant and antiapoptotic activities.

Açaí (Euterpe Oleraceae Mart.) Seeds Regulate NF-κB and Nrf2/ARE Pathways Protecting Lung against Acute and Chronic Inflammation.

BACKGROUND/AIMS: Respiratory diseases are the world's biggest cause of mortality and disability. Specific nutrients have been proposed to positively affect disease progression as novel therapy alternatives to glucocorticosteroids. There has been a lot of attention in the possible health advantages of dietary assumption of Açai Seeds, popular native fruit found in the Amazon region which is rich in bioactive compounds. Until today nobody investigated the beneficial property of Açai Seeds administration in lung disease. METHODS: In our study we use two model of lung disease: for acute lung disease we use an intrapleural injection of Carrageenan; for chronic disease we used an intratracheal instillation of bleomycin. Açai Seeds was administered orally dissolved in saline. RESULTS: We found that Açai Seeds was able to reduce histological alteration, cells infiltration, pro inflammatory cytokine release, inflammation, and oxidative stress in both acute and chronic model of lung disease. CONCLUSION: Our data clearly demonstrate for the first time that Açai Seeds administration was useful against lung disease by the reduction of NF-κB nuclear translocation and by the stimulation of Nrf2/ARE pathways promoting the physiological antioxidant defense.

Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update.

Fibromyalgia is a syndrome characterized by chronic and widespread musculoskeletal pain, often accompanied by other symptoms, such as fatigue, intestinal disorders and alterations in sleep and mood. It is estimated that two to eight percent of the world population is affected by fibromyalgia. From a medical point of view, this pathology still presents inexplicable aspects. It is known that fibromyalgia is caused by a central sensitization phenomenon characterized by the dysfunction of neuro-circuits, which involves the perception, transmission and processing of afferent nociceptive stimuli, with the prevalent manifestation of pain at the level of the locomotor system. In recent years, the pathogenesis of fibromyalgia has also been linked to other factors, such as inflammatory, immune, endocrine, genetic and psychosocial factors. A rheumatologist typically makes a diagnosis of fibromyalgia when the patient describes a history of pain spreading in all quadrants of the body for at least three months and when pain is caused by digital pressure in at least 11 out of 18 allogenic points, called tender points. Fibromyalgia does not involve organic damage, and several diagnostic approaches have been developed in recent years, including the analysis of genetic, epigenetic and serological biomarkers. Symptoms often begin after physical or emotional trauma, but in many cases, there appears to be no obvious trigger. Women are more prone to developing the disease than men. Unfortunately, the conventional medical therapies that target this pathology produce limited benefits. They remain largely pharmacological in nature and tend to treat the symptomatic aspects of various disorders reported by the patient. The statistics, however, highlight the fact that 90% of people with fibromyalgia also turn to complementary medicine to manage their symptoms.

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility.

Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1ß, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA.

Consumption of Anacardium Occidentale L. (Cashew Nuts) Inhibits Oxidative Stress through Modulation of the Nrf2/HO-1 and NF-kB Pathways.

Ischemia/reperfusion injury is a severe disorder associated with a high mortality. Several antioxidant and pharmacological properties of cashew nuts (Anacardium occidentale L.) and its metabolites from different countries have recently been described. It is a medicinal plant with important therapeutic effects. This study aimed to verify the effect of an oral administration of cashew nuts in a rat model of ischemia/reperfusion (I/R). Adult male rats were subjected to intestinal I/R injury by clamping the superior mesenteric artery for 30 min and then allowing animals to 1 h of reperfusion. Rats subjected to I/R of the gut showed a significant increase in different biochemical markers. In particular, we evaluated lipid peroxidation, tissue myeloperoxidase activity, protein carbonyl content, reactive oxygen species generation and decreased antioxidant enzyme activities. Western blot analysis showed the activation of the NRF2 and NF-kB pathways. Increased immunoreactivity to nitrotyrosine, PARP, P-selectin, and ICAM-1 was observed in the ileum of rats subjected to I/R. Administration of cashew nuts (100 mg/kg) significantly reduced the mortality rate, the fall in arterial blood pressure, and oxidative stress and restored the antioxidant enzyme activities by a mechanism involving both NRF2 and NF-kB pathways. Cashew nuts treatments reduced cytokines plasma levels, nitrotyrosine, and PARP expression as well as adhesion molecules expressions. Additionally, cashew nuts decreased the intestinal barrier dysfunction and mucosal damage, the translocation of toxins and bacteria, which leads to systemic inflammation and associated organs injuries in particular of liver and kidney. Our study demonstrates that cashew nuts administration exerts antioxidant and pharmacological protective effects in superior mesenteric artery occlusion-reperfusion shock.

Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury.

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 µg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1ß), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

Cashew (Anacardium occidentale L.) Nuts Counteract Oxidative Stress and Inflammation in an Acute Experimental Model of Carrageenan-Induced Paw Edema.

BACKGROUND: Anacardium occidentale L. is a medicinal plant with powerful anti-oxidative and anti-inflammatory properties. Acute inflammatory events cause tissue alterations, decrease of anti-oxidative endogenous enzymes such as superoxide dismutase, catalase and glutathione, neutrophils infiltration, increase in the activities of myeloperoxidase, malondialdehyde, and pro-inflammatory release. METHODS: Paw edema was induced by subplantar injection of carrageenan into the right hind paw in rats, but 30 min before a group of animals were orally treated with 100 mg/kg of cashew nuts to evaluate the anti-inflammatory and anti-oxidative response. RESULTS: In the present work, we found that (1) cashew nuts reduced the development of carrageenan-induced paw edema limiting the formation of edema and pain; (2) cashew nuts ameliorated the diminutions of the anti-oxidative enzymes caused by carrageenan injection; (3) cashew nuts decreased myeloperoxidase malondialdehyde activity induced by carrageenan; and (4) cashew nuts acted by blocking pro-inflammatory cytokines response and nitrate/nitrite formation stimulated by carrageenan injection. CONCLUSIONS: The mechanisms of anti-inflammatory and analgesic effects exerted by cashew nuts were relevant to oxygen free radical scavenging, anti-lipid peroxidation, and inhibition of the formation of inflammatory cytokines.

The Role of Cashew (Anacardium occidentale L.) Nuts on an Experimental Model of Painful Degenerative Joint Disease.

Osteoarthritis is a progressive joint disease characterized by the activation of different molecular mediators, including proinflammatory cytokines, reactive oxygen species, metalloproteinases and nociceptive mediators. Anacardium occidentale L. is a medicinal plant with anti-oxidative and anti-inflammatory properties. In this study we evaluate the effects of cashew nuts (from Anacardium occidentale L.) oral administration on an experimental model of painful degenerative joint disease. Monosodium iodoacetate (MIA) was intraarticularly injected, and cashew nuts were orally administered three times per week for 21 days, starting the third day after MIA injection. Nociception was evaluated by a Von Frey filament test, and motor function by walking track analysis at 3, 7, 14 and 21 days after osteoarthritis. Histological and biochemical alteration were examined at the end of the experiment. Cashew nuts administration reduced pain-like behavior and showed antioxidant activities, restoring biochemical serum parameters: glutathione (GSH), catalase (CAT) levels, glutathione peroxidase (GPx) activity and lipid peroxidation. Moreover, cashew nuts ameliorated radiographic and histological alteration, resulting in decreased cartilage degradation, pro-inflammatory cytokines and metalloproteinases levels and mast cells recruitment. Our results demonstrated that the oral assumption of cashew nuts counteracts the inflammatory and oxidative process involved in osteoarthritis.

N-acetyl-L-cysteine reduces Leishmania amazonensis-induced inflammation in BALB/c mice.

BACKGROUND: Leishmaniasis is a emergent disease characterized by different clinical manifestations in both humans and dogs. Predominant clinical features of cutaneous leishmaniasis are ulcerative painless skin lesions. Several data reported that pain is associated with human and dog leishmaniasis, out with areas of painless ulcerative lesions per se. Actually, current medications used for leishmaniasis management are characterized by several side effects and, in addition, some cases of the disease are refractory to the treatment. On this background it is mandatory the identification of new and safe candidates for designing less toxic and low-cost remedies. Therefore, the search for new leishmanicidal compounds is indispensable. METHODS: In the present paper we investigated the effect of orally N-acetyl-L-cysteine (NAC) supplementation at dose of 200 mg/Kg for 10 weeks, in subcutaneous Leishmania (L). amazonensis infected BALB/c mice. And evaluating the effect of NAC on inflammatory response such as TNF-α, IL-6, IL-1ß levels, and on thermal and mechanical hyperalgesia. RESULTS: In the present paper we showed how NAC supplementation affected parameters of oxidative stress (GSH, MDA, SOD), inflammation such as cytokines levels (IL-1ß, IL-6, TNFα) and mast cell activation and consequently on induced pain, during leishmaniosis in BALB\c mice. CONCLUSIONS: The findings of our study provided the scientific data demonstrating that L. amazonensis infection induces inflammation and pain in BALB/c mice that are reversed by administration of NAC.

Therapeutic Efficacy of Palmitoylethanolamide and Its New Formulations in Synergy with Different Antioxidant Molecules Present in Diets.

The use of a complete nutritional approach seems increasingly promising to combat chronic inflammation. The choice of healthy sources of carbohydrates, fats, and proteins, associated with regular physical activity and avoidance of smoking is essential to fight the war against chronic diseases. At the base of the analgesic, anti-inflammatory, or antioxidant action of the diets, there are numerous molecules, among which some of a lipidic nature very active in the inflammatory pathway. One class of molecules found in diets with anti-inflammatory actions are ALIAmides. Among all, one is particularly known for its ability to counteract the inflammatory cascade, the Palmitoylethanolamide (PEA). PEA is a molecular that is present in nature, in numerous foods, and is endogenously produced by our body, which acts as a balancer of inflammatory processes, also known as endocannabionoid-like. PEA is often used in the treatment of both acute and chronic inflammatory pathologies, either alone or in association with other molecules with properties, such as antioxidants or analgesics. This review aims to illustrate an overview of the different diets that are involved in the process of opposition to the inflammatory cascade, focusing on capacity of PEA and new formulations in synergy with other molecules.

Co-ultraPEALut: Role in Preclinical and Clinical Delirium Manifestations.

BACKGROUND: Delirium is a disorder in awareness, attention and cognition. Pathophysiologically it is a response to stress. Postoperative delirium (POD) is a usual complication in aged patients following hip fracture surgery. Neuroinflammation is an important factor linked with the progress of POD. Though there are no efficient cures for delirium the endocannabinoid system may have a role in neuropsychiatric disorders. OBJECTIVE: Therefore, we examined the effects of co-ultramicronized PEALut (co-ultraPEALut) in the LPS murine model of delirium and in elderly hip fractured patients. METHODS: In the preclinical study, mice were injected intraperitoneally (i.p.) with Escherichia coli LPS (10 mg/kg). Co-ultraPEALut (1 mg/kg o.s.) was administered 1h before LPS injection or 1h and 6h after LPS injection or 1h before LPS injection and 1h and 6h after LPS. In the clinical study, the effects of Glialia® (co-ultramicronized 700 mg PEA + 70 mg luteolin) administration was evaluated in elderly hip fractured patients with an interventional, randomized, single-blind, monocentric study. RESULTS: Administration of co-ultraPEALut to LPS-challenged mice ameliorated cognitive dysfunctions and locomotor activity; moreover, it reduced inflammation and apoptosis, while stimulating antioxidant response and limiting the loss of neurotrophins. In the clinical study, the results obtained demonstrated that administration of Glialia® to these surgical patients prevented the onset of POD and attenuated symptom intensity and their duration. CONCLUSION: Therefore, the results obtained enhanced the idea that co-ultraPEALut may be a potential treatment to control cognitive impairment and the inflammatory and oxidative processes associated with delirium.

Effects of a new compound containing Palmitoylethanolamide and Baicalein in myocardial ischaemia/reperfusion injury in vivo.

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is the principal cause of death, happens after prolonged obstruction of the coronary arteries.  The first intervention to limit myocardial damage is directed to restoration of perfusion, to avoid inflammatory response and a significant oxidative stress triggered by infarction. Palmitoylethanolamide (PEA), is a well-known fatty acid amide-signaling molecule that possess an important anti-inflammatory and analgesic effects. PEA does not hold the ability to inhibit free radicals formation. Baicalein, a bioactive component isolated from a Chinese herbal medicine, has multiple pharmacological activities, such as a strong anti-oxidative effects. PURPOSE: A combination of PEA and Baicalein could have beneficial effects on oxidative stress produced by inflammatory response. STUDY DESIGN: In the present study we explored the effects of composite containing PEA and Baicalein in a model of myocardial I/R injury. METHODS: Myocardial ischemia/reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-Baicalein (9:1), was administered (10 mg/kg) 5 min before the end of ischemia and 1 h after reperfusion. RESULTS: In this study, we clearly demonstrated that PEA-Baicalein treatment decreases myocardial tissue injury, neutrophils infiltration, markers for mast cell activation expression as chymase and tryptase and pro-inflammatory cytokines production (TNF-α, IL-1ß). Moreover, PEA-Baicalein treatment reduces stress oxidative and modulates Nf-kB and apoptosis pathways. CONCLUSION: These results support the idea that the association between PEA and Baicalein should be a potent candidate for the treatment of myocardial I/R injury.

Neuroprotective Effect of Artesunate in Experimental Model of Traumatic Brain Injury.

Traumatic brain injuries (TBI) are an important public health challenge. In addition, subsequent events at TBI can compromise the quality of life of these patients. In fact, TBI is associated with several complications for both long and short term, some evidence shows how TBI is associated with a decline in cognitive functions such as the risk of developing dementia, cerebral atrophy, and Parkinson disease. After the direct damage from TBI, a key role in TBI injury is played by the inflammatory response and oxidative stress, that contributes to tissue damage and to neurodegenerative processes, typical of secondary injury, after TBI. Given the complex series of events that are involved after TBI injury, a multitarget pharmacological approach is needed. Artesunate is a more stable derivative of its precursor artemisin, a sesquiterpene lactone obtained from a Chinese plant Artemisia annua, a plant used for centuries in traditional Chinese medicine. artesunate has been shown to be a pluripotent agent with different pharmacological actions. therefore, in this experimental model of TBI we evaluated whether the treatment with artesunate at the dose of 30 mg\Kg, had an efficacy in reducing the neuroinflammatory process after TBI injury, and in inhibiting the NLRP3 inflammasome pathway, which plays a key role in the inflammatory process. We also assessed whether treatment with artesunate was able to exert a neuroprotective action by modulating the release of neurotrophic factors. our results show that artesunate was able to reduce the TBI-induced lesion, it also showed an anti-inflammatory action through the inhibition of Nf-kb, release of proinflammatory cytokines IL-1ß and TNF-α and through the inhibition NLRP3 inflammasome complex, furthermore was able to reduce the activation of astrocytes and microglia (GFAP, Iba-1). Finally, our results show that the protective effects of artesunate also occur through the modulation of neurotrophic factors (BDNF, GDNF, NT-3) that play a key role in neuronal survival.

Effects of different natural extracts in an experimental model of benign prostatic hyperplasia (BPH).

OBJECTIVE AND DESIGN: To characterize the impact of inflammatory process and oxidative stress in the degree of benign prostatic hyperplasia (BPH), a common condition in which chronic inflammation plays a crucial role, we investigated the effect of different plant extract preparations in an in vivo model of BPH as new therapeutic target. MATERIAL: BPH was made in rats with daily administration of testosterone propionate (3 mg/kg) for 14 days. TREATMENT: Rats were randomized into different groups to receive oral administration of plant extract preparations: Serenoa repens with selenium (SeR 28.5 mg/kg associated with Se 0.005 mg/kg), Teoside (2 mg/kg), and Puryprost (14 mg/kg containing Teoside 50% 2 mg/kg and Epilobium 12 mg/kg). METHODS: After 14 days, rats were killed and histological changes, prostate weight and apoptotic pathways were assayed. RESULTS: The results obtained demonstrated that the association of treatments reduced prostate weight and hyperplasia, while treatment with Puryprost demonstrated a greater trend of protection compared to the other treatments. CONCLUSION: Thus, our results indicate that plant extract could be considered as new useful therapy in the treatment of BPH with particular attention on Puryprost that represents a rational approach to reduce BPH through modulation of inflammatory process and anti-oxidant process.

The Anti-Inflammatory and Antioxidant Potential of Pistachios (Pistacia vera L.) In Vitro and In Vivo.

Several reports have demonstrated the effectiveness of pistachio against oxidative stress and inflammation. In this study, we investigate if polyphenols extracts from natural raw shelled pistachios (NP) or roasted salted pistachio (RP) kernels have anti-inflammatory and antioxidant properties at lower doses than reported previously, in both in vitro and in vivo models. The monocyte/macrophage cell line J774 was used to assess the extent of protection by NP and RP pistachios against lipopolysaccharide (LPS)-induced inflammation. Moreover, antioxidant activity of NP and RP was assessed in an in vivo model of paw edema in rats induced by carrageenan (CAR) injection in the paw. Results from the in vitro study demonstrated that pre-treatment with NP (0.01, 0.1 and 0.5 mg/mL) and RP (0.01 and 0.1 mg/mL) exerted a significant protection against LPS induced inflammation. Western blot analysis showed NP reduced the degradation of IκB-α, although not significantly, whereas both NP and RP decreased the TNF-α and IL-1ß production in a dose-dependent way. A significant reduction of CAR-induced histological paw damage, neutrophil infiltration and nitrotyrosine formation was observed in the rats treated with NP. These data demonstrated that, at lower doses, polyphenols present in pistachios possess antioxidant and anti-inflammatory properties. This may contribute toward a better understanding of the beneficial health effects associated with consumption of pistachios.

Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice.

Polyphenols have been described to have a wide range of biological activities, and many reports, published during recent years, have highlighted the beneficial effects of phenolic compounds, illustrating their promising role as therapeutic tools in several acute and chronic disorders. The purpose of study was to evaluate, in an already-assessed model of lung injury caused by bleomycin (BLM) administration, the role of resveratrol and quercetin, as well as to explore the potential beneficial properties of a mango leaf extract, rich in mangiferin, and a grape leaf extract, rich in dihydroquercetin (DHQ), on the same model. Mice were subjected to intra-tracheal administration of BLM, and polyphenols were administered by oral route immediately after BLM instillation and daily for 7 d. Treatment with resveratrol, mangiferin, quercetin and DHQ inhibited oedema formation and body weight loss, as well as ameliorated polymorphonuclear infiltration into the lung tissue and reduced the number of inflammatory cells in bronchoalveolar lavage fluid. Moreover, polyphenols suppressed inducible nitric oxide synthase expression, and prevented oxidative and nitroxidative lung injury, as shown by the reduced nitrotyrosine and poly (ADP-ribose) polymerase levels. The degree of apoptosis, as evaluated by Bid and Bcl-2 balance, was also suppressed after polyphenol treatment. Finally, these natural products down-regulated cyclo-oxygenase-2, extracellular signal-regulated kinase phosphorylated expression and reduced NF-κBp65 translocation. Our findings confirmed the anti-inflammatory effects of resveratrol and quercetin in BLM-induced lung damage, and highlight, for the first time, the protective properties of exogenous administration of mangiferin and DHQ on experimental pulmonary fibrosis.