Anti-inflammatory effect of Arnica montana in a UVB radiation-induced skin-burn model in mice.

Background: ultraviolet radiation types A and B (UV) (400-315nm and 315-280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that has been widely studied for containing anti-inflammatory, healing and analgesic properties capable of preventing or ameliorating lesions. Here, we investigated the therapeutic effect of topical application of Arnica montana after UVB-induced cutaneous injuries in mice.Methods: mice were exposed to UVB radiation (Philips TL40W/12 RS lamp) in a period of 3 hours. After one hour of radiation exposure, the animals were treated with topical application of Arnica montana ointment (250 mg/g) in the ear. At the time of 16 hours after treatment, the parameters of edema, oxidative stress and inflammatory reaction were measured in the ear of mice.Results: our results demonstrated that topical treatment with Arnica montana reduced the UVB-induced inflammatory response as demonstrated by the reduction of ear edema, inhibition of myeloperoxidase activation, decrease of nuclear factor kappa B levels and reduction of proinflammatory cytokines levels, such as interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma. In addition, Arnica montana ameliorated oxidative damage mediated by UVB radiation, as demonstrated by the reduction of lipid peroxidation, protein oxidation and increase of tissue antioxidant capacity and glutathione levels in the ear.Conclusion: we concluded that Arnica montana ointment is effective in alleviating the auricular inflammatory process and oxidative damage induced by acute UVB radiation, sustaining the traditional use of Arnica montana for the treatment of skin disorders.

Ilex paraguariensis Attenuates Changes in Mortality, Behavioral and Biochemical Parameters Associated to Methyl Malonate or Malonate Exposure in Drosophila melanogaster.

Methylmalonic acidemia is a genetic disease characterized by accumulation of organic acids, such as methylmalonic (MMA) and malonic (MA) acids. Considering that the accumulation of MMA and MA causes several damages due to oxidative stress, antioxidants are thought to play a pivotal role in preventing deleterious effects associated with exposure to such compounds. Ilex paraguariensis (IP) was used here to test the hypothesis that supplementation with the aqueous extract of this plant could exert protective effect against MMA or MA induced mortality, behavioral and/or biochemical changes in Drosophila melanogaster (DM). Initially, a curve time- and dose-response to MMA (1-10 mM), MA (1-10 mM) and IP (63-500 µM) was performed. Thereafter, flies were concomitantly exposed to MA (5 mM), MMA (5 mM) and/or IP (250 µg/mL) during 15 days for survival assay, and for 48 hs to MA (1 or 5 mM), MMA (1 or 5 mM) and/or IP (250 µg/mL) for subsequent investigations. Both MMA and MA exposure resulted in higher incidence of mortality, a worse performance in the negative geotaxis assay and increased locomotion in open-field test as compared with control group. Furthermore, a marked increase in non-protein thiol (NPSH) and in thiobarbituric acid reactive substances (TBARS) levels, decrease in superoxide dismutase (SOD), catalase and acetylcholinesterase (AChE) activities, and decrease in MTT and resazurin reduction were noted in MMA or MA treated groups. IP treatment offered significant protection against all alterations associated to MMA or MA exposure. This study confirm the hypothesis that supplementation with IP offers protection against changes associated to MMA or MA exposure in DM, due, at least in part, to its antioxidant effect.

Blackberry juice anthocyanidins limit cisplatin-induced renal pathophysiology in mice.

Some studies have showed that intake of blackberry juice (BBJ) can prevent urinary tract infections. However, there is a lack of studies that evaluate the mechanisms by which BBJ has protective effect. Thus, the aim of current study was to evaluate the effects of BBJ supplementation on cisplatin-induced renal pathophysiology in mice. Mice were supplemented with BBJ (10 mL/kg) for seven days. One hour after the last supplementation with BBJ, mice received cisplatin (10 mg/kg, i.p.). Seventy-two hours after cisplatin administration, blood was collected and biochemical analysis were performed (urea and creatinine), kidney was dissected and utilized in histological and oxidative evaluations. Cisplatin caused severe injury in renal tissue, in markers of renal damage (urea and creatinine) generated increased of plasmatic levels. Besides that, the cisplatin induced decreased of enzymes activities in renal tissue (superoxide dismutase, glutathione S-transferase and catalase). In contrast, BBJ supplementation protected against histopathological alterations through decreased in urea and creatinine levels and modulation of catalase enzyme activity. Thus, BBJ supplementation protected the renal system of mice from deleterious effects. We suggest that high concentrations of Cyanidin 3-O-glucoside and Cyanidin 3-O-rutinoside are responsible for antioxidant role of BBJ supplementation in renal pathophysiology induced by cisplatin exposure. Also, these results reinforcing the importance of including BBJ in the human diet aimed at preventing renal diseases.

Aging exacerbates cognitive and anxiety alterations induced by an intracerebroventricular injection of amyloid-ß1-42 peptide in mice.

An increasing body of evidence indicates that the activation of indoleamine-2,3-dyoxigenase (IDO), a first and rate-limiting enzyme in the kynurenine (KYN) pathway, is involved in Aß1-42-neurotoxicity and AD pathogenesis. We have reported for the first time that brain IDO activation is related to Aß1-42 exposure in young mice. Because aging is characterized by a brain dyshomeostasis and because it remains the most dominant risk factor for AD, the purpose of this study was to determine whether aging is associated with a higher sensitivity to behavioural and neurochemical alterations elicited by an intracerebroventricular (i.c.v.) injection of Aß1-42 (400 pmol/mice), and whether KYN pathway is involved in these effects. We confirmed that aged mice displayed higher cognitive deficit in the object recognition test and higher anxiety-like behaviour in the elevated plus-maze and open field tests after the Aß1-42 administration. Aged mice also responded to Aß1-42 with a higher deficiency of brain-derived neurotrophic factor, glutathione levels and total radical-trapping antioxidant capacity, a higher IDO activity, and a higher KYN and KYN/tryptophan ratio in the prefrontal cortex and hippocampus. These effects of Aß1-42 were associated with a higher proinflammatory status, as measured by higher levels of interleukin-6, lower levels of interleukin-10 and higher expression of glial fibrillary acidic protein (GFAP) and allograft inflammatory factor 1 (Iba1) in the brain of aged mice. These results represent primary evidence suggesting that age-associated inflammatory signature and down-regulation of neuroprotectants in the brain render aged mice more vulnerable to Aß1-42-induced memory loss, anxiety symptoms and KYN pathway dysregulation.

Activation of Brain Indoleamine-2,3-dioxygenase Contributes to Depressive-Like Behavior Induced by an Intracerebroventricular Injection of Streptozotocin in Mice.

There is a lack of information concerning the molecular events underlying the depressive-like effect of an intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. The elevated activity of the tryptophan-degrading enzyme indoleamine-2,3-dioxygenase (IDO) has been proposed to mediate depression in inflammatory disorders. In the present study, we reported that ICV-STZ activates IDO in the hippocampus of mice and culminates in depressive-like behaviors, as measured by the increased duration of immobility in the tail suspension test and decreased sucrose intake in the sucrose preference test. The blockade of IDO activation by the IDO inhibitor 1-methyltryptophan (1-MT) prevents the development of depressive-like behaviors and attenuates STZ-induced up-regulation of proinflammatory cytokines in the hippocampus. 1-MT abrogates kynurenine production and normalizes brain-derived neurotrophic factor (BDNF) and the kynurenine/tryptophan ratio, but does not protect the biomarkers of the serotonin (5-HT) system in the hippocampus of STZ-injected mice. These results implicate IDO as a critical molecular mediator of STZ-induced depressive-like behavior, likely through activation of the kynurenine pathway and subsequent reduction of BDNF levels. Impairment of the 5-HT system may reflect the inflammatory response induced by STZ and also contributes to observed depression symptoms. The present study not only provides evidence that IDO plays a critical role in mediating inflammation-induced depression but also supports the notion that neuroinflammation and the kynurenine pathway are important targets for novel therapeutic drugs for depression. In addition, this study provides new insights on the neurobiological mechanisms underlying ICV-STZ and indicates that this model could be employed in preclinical research of depression.

Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice.

Depression is one of the most common mental disorders and a primary cause of disability. To better treat patients suffering this illness, elucidation of the underlying psychopathological and neurobiological mechanisms is urgently needed. Based on the above-mentioned evidence, we sought to investigate the effects of neuropeptide Y (NPY) treatment in tricyclic antidepressant treatment-resistant depression induced by adrenocorticotropic hormone (ACTH) administration. Mice were treated with NPY (5.84, 11.7 or 23.4mmol/µl) intracerebroventricularly (i.c.v.) for one or five days. The levels of serum corticosterone, tryptophan (TRP), kynurenine (KYN), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and indoleamine 2,3-dioxygenase (IDO) activity in the hippocampus were analyzed. The behavioral parameters (depressive-like and locomotor activity) were also verified. This study demonstrated that ACTH administration increased serum corticosterone levels, KYN, 5-HIAA levels, IDO activity (hippocampus), immobility in the forced swimming test (FST) and the latency to feed in the novelty suppressed feeding test (NSFT). In addition, ACTH administration decreased the BDNF and NGF levels in the hippocampus of mice. NPY treatment was effective in preventing these hormonal, neurochemical and behavioral alterations. It is suggested that the main target of NPY is the modulation of corticosterone and neuronal plasticity protein levels, which may be closely linked with pharmacological action in a model of tricyclic antidepressant treatment-resistant depression. Thus, this study demonstrated a protective effect of NPY on the alterations induced by ACTH administration in mice, indicating that it could be useful as a therapy for the treatment of tricyclic antidepressant treatment-resistant depression.

Novelty facilitates the persistence of aversive memory extinction by dopamine regulation in the hippocampus and ventral tegmental area.

Aversive memory extinction comprises a novel learning that blocks retrieving a previously formed traumatic memory. In this sense, aversive memory extinction is an excellent tool for decreasing fear responses. However, this tool it's not effective in the long term because of original memory spontaneous recovery. Thus, searching for alternative strategies that strengthen extinction learning is essential. In the current study, we evaluated the effects of a novel context (i.e., novelty) exposure on aversive memory extinction enhancement over days and the dopaminergic system requirement. Given the purpose, experiments were conducted using 3-month-old male Wistar rats. Animals were trained in inhibitory avoidance (IA). Twenty-four hours later, rats were submitted to a weak extinction protocol. Still, 30 min before the first extinction session, animals were submitted to an exploration of a novel context for 5 min. After, memory retention and persistence were evaluated 24 h, 3, 7, 14, and 21 days later. The exposition of a novel context caused a decrease in aversive responses in all days analyzed and an increase in dopamine levels in the hippocampus. The intrahippocampal infusion of dopamine in the CA1 area or the stimulation of the ventral tegmental area (VTA) by a glutamatergic agonist (NMDA) showed similar effects of novelty. In contrast, VTA inhibition by a gabaergic agonist (muscimol) impaired the persistence of extinction learning induced by novelty exposition and caused a decrease in hippocampal dopamine levels. In summary, we show that novel context exposure promotes persistent aversive memory extinction, revealing the significant role of the dopaminergic system.

HDAC3 inhibition protects against peripheral and central alterations in an animal model of obesity.

BACKGROUND: Obesity is a multifactorial disease with epigenetic manifestations that increases the prevalence of associated comorbidities such as metabolic syndrome, cardiovascular dysfunction, and major depression disorder. Given the aforementioned, a search for new pharmacological alternatives for the treatment of this disease is necessary. The current study aimed to evaluate the effects of histone deacetylase-3 (HDAC3) inhibition caused by RGFP966 (a benzamide-type HDAC inhibitor selective for HDAC3) administration, in an animal model of obesity induced by high-fat diet (HFD). METHODS: Adult male mice C57BJ/6 were fed with a normal pellet diet (NPD) or HFD for 120 days. The HDAC3 inhibitor (RGFP966; 10 mg/kg; sc) was administered on the 91st to 120th day of the experiment (per 30 days). After the last inhibitor administration, animals were euthanized, blood was collected, and the hippocampus was removed for biochemical determinations. RESULTS: In an overall manner, the administration of RGFP966 protected against changes in body weight gain, glucose, insulin, lipid profile, adipokines, and increase of hippocampal proinflammatory cytokines levels caused by HFD. CONCLUSION: Therefore, HDAC3 inhibition can represent a promising pharmacological target for the treatment of obesity.

Surface-functionalized curcumin-loaded polymeric nanocapsules could block apomorphine-induced behavioral changes in rats.

BACKGROUND: Surface functionalization enhances the properties and characteristics of polymeric nanocapsules (NCs) mainly due to the surface charge, surfactants, and polymer coating type. Curcumin (CUR) is a bioactive compound with several proven pharmacological properties and low bioavailability. This study aimed to develop anionic (poly-ɛ-caprolactone; PCL) and cationic (Eudragit® RS100 (EUD)) NCs prepared with sorbitan monostearate (Span 60®) or sorbitan monooleate (Span 80®), coated with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and optimized using 23 factorial analysis. Subsequently, the biological activity was evaluated. METHODS: A two-level, three-factor design (polymer, Span type, and TPGS concentration) was used. The biological effects of CUR-loaded TPGS-coated cationic and anionic NCs were assessed in apomorphine-induced stereotyped behavior in rats. RESULTS: The type of polymer (anionic or cationic) and Span® had a factorial influence on the physical and chemical characteristics of NCs according to the changes in TPGS concentrations. Both cationic and anionic CUR-NCs could block apomorphine-induced behavioral changes. CONCLUSIONS: The CUR-loaded TPGS-coated NCs proved to be a promising brain delivery system.

In vivo and in vitro per se effect evaluation of Polycaprolactone and Eudragit® RS100-based nanoparticles.

Biodegradable polymeric nanocapsules (NC) present incredible characteristics as drug nanocarriers that optimize drug targeting. However, However, a more detailed isolated effect of polymer-based nanoparticles as drug carriers is required. This work aimed to evaluate the per se effect of blank-NC (NC-B) with different surface characteristics both in vitro and in vivo toxicity. NC1-B (Polysorbate 80 coated poly(ɛ-caprolactone) NC), NC2-B (polyethylene glycol 6000 coated poly(ɛ-caprolactone) NC), NC3-B (chitosan-coated poly(ɛ-caprolactone) NC) and NC4-B (Eudragit® RS100 NC) were prepared by nanoprecipitation method. Formulations were characterized by particle size, zeta potential, and pH. The in vitro cytotoxicity tests against tumor cell lines were performed (HepG2 and MCF-7). Antiviral activity was evaluated by MTT in Vero cells infected with HSV-1 (KOS strain). In vivo evaluation was performed in apomorphine-induced stereotypy in Wistar rats and locomotor activity distance, head movements, and rearing behavior were measured. NC1-B, NC2-B, NC3-B, and NC4-B had a diameter under 350 nm. The pH and zeta potential of formulations varied according to their coating. For in vitro evaluation of antitumor activity and antiviral activity, one-way ANOVA showed no significant differences in cell viability. In vivo tests showed low neurological effects. In conclusion, different surface characteristics of NC-B did not demonstrate toxicity against the evaluated cell lines HepG2 and MCF-7, antiviral effect against HSV-1, and the neurological effects in a stereotyping model were low and may be attributed to the per se effect of NC-B.

Evaluation of curcumin-loaded polymeric nanocapsules with different coatings in chick embryo model: influence on angiogenesis, teratogenesis and oxidative stress.

BACKGROUND: Curcumin (CUR) is a bioactive compound with several proven pharmacological properties. However, the major limitation for therapeutic use of CUR is its low bioavailability. In this sense, an alternative to this question is the use of polymeric nanocapsules (NC) as drug/nutraceutical delivery systems. Thus, the aim of current study was to assess the effect of CUR-loaded NC and their different coatings in chick embryo model, evaluating angiogenic, teratogenic and oxidative stress parameters. METHODS: The physicochemical characterization of unloaded and loaded NC with different coatings: (U-NC (P80), U-NC (PEG), U-NC (EUD), U-NC (CS), CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS)) were performed. After 9 days of incubation, eggs were treated (10 mL/kg eggs; via injection) with NC (unloaded and loaded with CUR) and CUR-solution. In sequence, hen's egg test-chorioallantoic membrane (HET-CAM), angiogenic assay, external abnormalities, weight of embryos and oxidative stress markers (TBARS, NPSH, ROS and CAT) were analyzed. RESULTS: CUR-NC (P80, PEG, EUD and CS) treatments caused antiangiogenic and non-teratogenic effects in chick embryo model. Still, CUR-NC (P80), CUR-NC (PEG), CUR-NC (EUD) and CUR-NC (CS) did not alter markers of oxidative stress (TBARS, NPSH, CAT) studied. Only CUR-NC (EUD) caused increase in ROS levels. CONCLUSION: Wherefore, these findings of present study represent a advance in research of drug/nutraceutical delivery systems.

Curcumin-loaded nanocapsules: Influence of surface characteristics on technological parameters and potential antimalarial activity.

The present study aimed to develop nanocapsules (NCs) loaded with curcumin (CCM) using different coatings, comparing the effect of these coatings on physicochemical properties of NCs. NCs were prepared by interfacial deposition of performed polymer, using different polymers as coatings (P80, PEG, Chitosan and Eudragit RS100®) and then, characterized in detail by different techniques (AFM, FTIR, DSC, XRD, among others). In vitro studies were performed, evaluating the release profile, cytotoxicity and antimalarial activity of CCM-loaded NCs. Overall, all CCM-loaded NCs samples exhibited typical characteristics as nanometric size, coating-dependent zeta potential, acidic pH value, span values below 2, homogeneous morphology and CCM-distribution in pseudophases of type VI (for all of coatings). Experimental results showed that CCM remains stable in lipid-core of NCs, maintaining its physicochemical and biological properties after nanoencapsulation process. In vitro release assays showed that nanoencapsulation was an efficient strategy to controlled release of CCM and P80-coated NCs presented slowest CCM-release considering all nanoformulations tested. Still, CCM-loaded NCs presented no cytotoxic effect. Also, all CCM-loaded NCs showed a perceptible antimalarial activity independently of their coatings (anionic and cationic), with more expressive results for CS-coated NCs. In conclusion, findings for CCM-loaded NCs and their different coatings seem to be a promising strategy to improve your biological activity.

Chrysin loaded lipid-core nanocapsules ameliorates neurobehavioral alterations induced by ß-amyloid1-42 in aged female mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a clinically and progressive loss of cognitive function, neuropsychiatric and behavioral disorders. Some studies showed that chrysin has antioxidant and anti-inflammatory properties. However, your bioavailability is relatively low. Therefore, the present study was designed to investigate the effects of chrysin loaded lipid-core nanocapsules (LNCs) on neurochemical and behavioral changes in a model of AD induced by ß-amyloid1-42 (Aß1-42) peptide in aged female mice. For this purpose, aged female mice received free chrysin (FC) (5 mg/kg, per oral, p.o.) or chrysin loaded LNCs (C1-LNC and C5-LNC) (1 or 5 mg/kg, p.o.) for 14 days after Aß1-42 administration (400 pmol, i.c.v.). Aß1-42 induced significant impairments on memory and learning (morris water maze task, object recognition and step-down-type passive avoidance), also caused oxidative stress, reduced the levels of brain-derived neurotrophic factor (BDNF), increased neuroinflammation in prefrontal cortex and hippocampus of aged animals. Thus, C1-LNC and C5-LNC displayed significant effect against Aß1-42, via attenuation of oxidative stress and neuroinflammation, modulation of neurochemical and behavioral changes in a model of AD. These results point to chrysin loaded LNCs (mainly C5-LNC) can be a promising biomedical tool and a new therapeutic approach for treatment and prevention of AD.

ORY supplementation mitigates acetaminophen-induced acute liver failure in male mice: role of oxidative stress and apoptotic markers.

The aim of the present study was to assess the possible protective effect of γ-oryzanol (ORY) supplementation in a model of acute liver failure (ALF) induced by acetaminophen (APAP) in mice. Male Swiss strain mice were supplemented with ORY (10 and 50 mg/kg, per oral route) daily for 7 days. One hour after the last supplementation, animals received APAP (300 mg/kg, intraperitoneal). Twenty-four hours after APAP administration, mice were euthanized, and biochemical and histopathological determinations were performed. Histopathological analysis revealed that APAP caused vascular congestion, loss of cellular structure, and cellular infiltration in hepatocytes. Moreover, it caused oxidative damage (enzymatic and non-enzymatic analysis of oxidative stress), with loss of hepatic function leading to cell apoptosis (apoptotic parameters). ORY supplementation (ORY-10 and ORY-50) protected against all changes in ALF model. Thus, the protective effect of ORY supplementation was due to modulation of antioxidant defenses avoiding the apoptotic process.

Involvement of kynurenine pathway in depressive-like behaviour induced by nandrolone decanoate in mice.

Nandrolone decanoate (ND) belongs to the class II of anabolic-androgenic steroids (AAS), which is composed of 19-nor-testosterone-derivatives. AAS represent a group of synthetic testosterone that is used in clinical treatment. However, these drugs are widely abused among individuals as a means of promoting muscle growth or enhancing athletic performance. AAS in general and ND in particular have been associated with several behavioral disturbances, such as anxiety, aggressiveness and depression. A factor that contributes to the development of depression is the brain activation of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme of kynurenine pathway (KP). In the present study, we examined the involvement of KP in depressive phenotype induced by a ND treatment (10 mg/kg/day/s.c., for 28 days) that mimics human abuse system (e.g. supraphysiological doses) in C57B/6J mice. Our results showed that ND caused depressive like-behavior in the tail suspension test and anhedonic-like state measured in the sucrose preference test. ND administration decreased the levels of brain-derived neurotrophic factor and neurotrophin-3 and reduced Na+,K+-ATPase activity in the hippocampus, striatum and prefrontal cortex. We also found that ND elicited KP activation, as reflected by the increase of IDO activity and kynurenine levels in these brain regions. Moreover, ND decreased serotonin levels and increased 5-hydroxyindoleacetic acid levels in the brain. Treatment with IDO inhibitor 1-methyl-dl-trypthophan (1 mg/kg/i.p.) reversed the behavioral and neurochemical alterations induced by ND. These results indicate for the first time that KP plays a key role in depressive-like behavior and neurotoxicity induced by supraphysiologicaldoses of ND in mice.

Curcumin-loaded lipid-core nanocapsules attenuates the immune challenge LPS-induced in rats: Neuroinflammatory and behavioral response in sickness behavior.

The purpose of current study was to evaluate the effect of curcumin (CUR) loaded lipid-core nanocapsules (CUR-LNC) treatment on neuroinflammatory and behavioral alterations in a model of sickness behavior induced by lipopolysaccharide (LPS) in rats. Rats were treated with CUR-LNC and CUR daily for 14 days. After the last treatments, sickness behavior was induced with LPS. Sickness behavior LPS-induced was confirmed by behavioral tests, an increase in levels of proinflammatory cytokines, decrease in levels of IL-10, overexpression of IDO-1 and IDO-2. In conclusion, CUR-LNC treatment attenuated the neuroinflammatory and behavioral changes caused in sickness behavior model.

Assessment of unloaded polymeric nanocapsules with different coatings in female rats: Influence on toxicological and behavioral parameters.

The unloaded polymeric nanocapsules (NCs) present incredible characteristics as drug carriers. However, the toxicity caused by NCs with different coatings is still a challenge for contemporary toxicology. Allied to this, preclinical studies are performed in males, disregarding possible gender-dependent toxicity. Thus, the aim of present study was to evaluate the influence of different NCs coatings on toxicological and behavioral parameters in female rats. The physicochemical characterization of NCs with different surface coatings: NC1 (Polysorbate 80), NC2 (PEG), NC3 (Eudragit®RS 100) and NC4 (Chitosan) were performed. Female rats were treated with saline, NC1, NC2, NC3 or NC4 daily for 14 days, p.o. After 24 h of last treatment, animals were submitted to behavioral tests. Only after behavioral tests, female rats were euthanized, organs were removed and weighted. After, histopathological, biochemical and oxidative stress analysis were performed. All NCs-coatings did not cause alterations in behavioral tests. For markers of hepatic, renal damage and lipid profile, the different coatings showed a low toxicity. NCs did not alter weight of organs and histopathological analysis. Also, all NCs-coatings did not modify redox balance in organs studied, only NC2 induced a increase of FRAP levels in intestine. This study demonstrated that the different NCs-coatings did not cause behavioral changes and showed a low toxicity in female rats.

Chrysin suppress immune responses and protects from experimental autoimmune encephalomyelitis in mice.

We investigated the effects of chrysin in the experimental autoimmune encephomyelitis (EAE), a multiple sclerosis (MS) animal model. EAE was induced using myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide in C57BL/6 mice. Chrysin reduced weight loss, attenuated clinical signs and blunted the EAE-induced increase in histone deacetylase (HDCA) activity, glycogen synthase kinase-3ß (GSK-3ß) levels and pro-inflammatory cytokine levels as well as in the EAE-induced decrease in histone acetyltransferases 3 and 4 (HAT3, HAT4). Altogether, results demonstrate beneficial effects and potential targets of chrysin in EAE.

The flavonoid chrysin protects against zearalenone induced reproductive toxicity in male mice.

The mycotoxin zearalenone (ZEA) has strong estrogenic effects and elicits reproductive toxicity. Chrysin is a natural flavonoid found in many plant and has a broad range of pharmacological activities, including anticancer, antioxidant and anti-inflammatory. The present study aimed to investigate the potential protective effects of chrysin against ZEA toxicity. Mice received chrysin (5 or 20 mg/kg; i.g.) for ten days, and then received a single injection of ZEA (40 mg/kg). Two days thereafter, blood and testes were collected. ZEA decreased number and motility of sperm, plasma testosterone levels, enzymatic (glutathione peroxidase, glutathione reductase, glutathione-S-transferase) and non-enzimatic defenses (reduced glutathione). Moreover, ZEA increased 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine levels, myeloperoxidase activity and levels of proinflammatory cytokines (interleukins-1ß and 6, tumor necrosis factor alpha). ZEA also decreased levels of anti-inflammatory cytokine interleukin-10 and increased activity of caspases 3 and 9. Chrysin treatment increased the number and motility of sperm, testosterone levels, restored antioxidant defenses and reduced the inflammation and apoptosis process. In summary, chrysin attenuated the toxic effects caused by ZEA in blood and testes of mice, suggesting a potential preventive treatment against the deleterious effects of ZEA.

Chrysin protects against behavioral, cognitive and neurochemical alterations in a 6-hydroxydopamine model of Parkinson's disease.

Parkinson's disease (PD) is an age-related neurodegenerative disorder that severely affects quality of life of patients and their families. The flavonoid chrysin (5,7-dihydroxylflavone) is a naturally occurring flavone with several pharmacological activities, including anti-inflammatory and anti-oxidative. We investigated the effects of a 28-day chrysin treatment (10 mg/kg/day, i.g.) on a model of PD induced by 6-OHDA in aged (20-month old) mice. We found a protective effect of chrysin on behavioral and cognitive alterations (rotational behavior, passive avoidance and Barnes maze tests), nitric oxide synthesis (NOx), lipid peroxidation (HNE), glutathione levels (GSH), reactive species levels (RS), neuroinflammation (interleukin-1 beta - IL-1ß and tumor necrosis factor alpha - TNF-α), Na+, K+-ATPase and nicotinamide adenine dinucleotide phosphate oxidase activity (NADPH oxidase) activities. In addition, chrysin protected against changes in striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels. In conclusion, chrysin improved several behavioral, cognitive and neurochemical parameters in a relevant preclinical model of PD in aged mice.