Role of Etanercept and Infliximab on Nociceptive Changes Induced by the Experimental Model of Fibromyalgia.

BACKGROUND: Fibromyalgia is a clinical condition that affects 1% to 5% of the population. No proper therapy has been currently found. It has been described that inflammation plays a central role in the nerve sensitizations that characterize the pathology. METHODS: This paper aimed to evaluate the efficacy of etanercept and infliximab in the management of pain sensitization. Fibromyalgia was induced by three injections once a day of reserpine at the dose of 1 mg/kg. Etanercept (3 mg/kg) and infliximab (10 mg/kg) were administered the day after the last reserpine injection and then 5 days after that. Behavioral analyses were conducted once a week, and molecular investigations were performed at the end of the experiment. RESULTS: Our data confirmed the major effect of infliximab administration as compared to etanercept: infliximab administration strongly reduced pain sensitization in thermal hyperalgesia and mechanical allodynia. From the molecular point of view, infliximab reduced the activation of microglia and astrocytes and the expression of the purinergic P2X7 receptor ubiquitously expressed on glia and neurons. Downstream of the P2X7 receptor, infliximab also reduced p38-MAPK overexpression induced by the reserpine administration. CONCLUSION: Etanercept and infliximab treatment caused a significant reduction in pain. In particular, rats that received infliximab showed less pain sensitization. Moreover, infliximab reduced the activation of microglia and astrocytes, reducing the expression of the purinergic receptor P2X7 and p38-MAPK pathway.

Role of Bevacizumab on Vascular Endothelial Growth Factor in Apolipoprotein E Deficient Mice after Traumatic Brain Injury.

Traumatic brain injury (TBI) disrupts the blood-brain barrier (BBB). Vascular endothelial growth factor (VEGF) is believed to play a key role in TBI and to be overexpressed in the absence of apolipoprotein E (ApoE). Bevacizumab, a VEGF inhibitor, demonstrated neuroprotective activity in several models of TBI. However, the effects of bevacizumab on Apo-E deficient mice are not well studied. The present study aimed to evaluate VEGF expression and the effects of bevacizumab on BBB and neuroinflammation in ApoE-/- mice undergoing TBI. Furthermore, for the first time, this study evaluates the effects of bevacizumab on the long-term consequences of TBI, such as atherosclerosis. The results showed that motor deficits induced by controlled cortical impact (CCI) were accompanied by increased brain edema and VEGF expression. Treatment with bevacizumab significantly improved motor deficits and significantly decreased VEGF levels, as well as brain edema compared to the control group. Furthermore, the results showed that bevacizumab preserves the integrity of the BBB and reduces the neuroinflammation induced by TBI. Regarding the effects of bevacizumab on atherosclerosis, it was observed for the first time that its ability to modulate VEGF in the acute phase of head injury prevents the acceleration of atherosclerosis. Therefore, the present study demonstrates not only the neuroprotective activity of bevacizumab but also its action on the vascular consequences related to TBI.

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.

Chronic Exposure to Vinclozolin Induced Fibrosis, Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis in Mice Kidney.

Vinclozolin is one of the most used fungicides in the control of fungi in fruits, vegetables, and ornamental plants. The effects of its exposure on different organs have been described, but information regarding its relevance to vinclozolin-induced nephrotoxicity is largely missing. This study focuses on the potential mechanism of vinclozolin-induced nephrotoxicity. CD1 male mice were administered vinclozolin (100 mg/kg) by oral gavage for 28 days. Vinclozolin administration decreased body weight over the treatment period and at the end of the experiment, increased the ratio of kidney weight to body weight and increased serum urea nitrogen and creatinine contents. Vinclozolin also induced histopathological alterations, including tubular dilatation and necrosis and impaired the integrity of the renal-tubular architecture and kidney fibrosis. The analyses conducted showed that vinclozolin administration altered the mRNA levels of mitochondrial function-related proteins (SIRT3, SIRT1, PGC-1α, TFAM, NRF1, VDAC-1, and Cyt c) and oxidative stress (increased lipid peroxidation and decreased total antioxidative capacity, catalase, and superoxide dismutase activities, glutathione levels, and glutathione peroxidase activity) in the kidneys. Furthermore, vinclozolin induced toxicity that altered Nrf2 signalling and the related proteins (HO-1 and NQO-1). Vinclozolin administration also affected both the extrinsic and intrinsic apoptotic pathways, upregulating the expression of proapoptotic factors (Bax, Caspase 3, and FasL) and downregulating antiapoptotic factor (Bcl-2) levels. This study suggests that vinclozolin induced nephrotoxicity by disrupting the transcription of mitochondrial function-related factors, the Nrf2 signalling pathway, and the extrinsic and intrinsic apoptotic pathways.

Chronic Exposure to Endocrine Disruptor Vinclozolin Leads to Lung Damage via Nrf2-Nf-kb Pathway Alterations.

Endocrine-disrupting substances (EDS) are common and pervasive in our environment and pose a serious risk to both human and animal health. Endocrine-disrupting compounds (EDCs) have been associated with a variety of detrimental human health effects, including respiratory issues, as a result of their ability to disrupt cell physiology. Vinclozolin ((RS)-3-(3,5-Dichlorophenyl)-5-methyl-5-vinyloxazolidine-2,4-dione) is a common dicarboximide fungicide used to treat plant diseases. Several studies have analyzed the effects of vinclozolin exposure on the reproductive system, but less is known about its effect on other organs such as the lung. Mice were exposed for 28 days to orally administered vinclozolin at a dose of 100 mg/kg. Vinclozolin exposure induced histological alterations and collagen depositions in the lung. Additionally, vinclozolin induced inflammation and oxidative stress that led to lung apoptosis. Our study demonstrates for the first time that the toxicological effects of vinclozolin are not limited to the reproductive system but also involve other organs such as the lung.

Correction: D'Amico et al. Toxic Exposure to Endocrine Disruptors Worsens Parkinson's Disease Progression through NRF2/HO-1 Alteration. Biomedicines 2022, 10, 1073.

Errors in Figures [...].

Toxic Effects of Gemcitabine and Paclitaxel Combination: Chemotherapy Drugs Exposure in Zebrafish.

Pharmaceuticals are widely recognized as potentially hazardous to aquatic ecosystems. In the last two decades, the constant intake of biologically active chemicals used in human healthcare has been related to the growing release of these agents into natural environments. As reported by several studies, various pharmaceuticals have been detected, mainly in surface water (seas, lakes, and rivers), but also in groundwater and drinking water. Moreover, these contaminants and their metabolites can show biological activity even at very low concentrations. This study aimed to evaluate the developmental toxicity of exposure to the chemotherapy drugs gemcitabine and paclitaxel in aquatic environments. Zebrafish (Danio rerio) embryos were exposed to doses of gemcitabine 15 µM in combination with paclitaxel 1 µM from 0 to 96 h post-fertilization (hpf) using a fish embryo toxicity test (FET). This study highlights that both gemcitabine and paclitaxel exposure at single non-toxic concentrations affected survival and hatching rate, morphology score, and body length after exposure in combination. Additionally, exposure significantly disturbed the antioxidant defense system and increased ROS in zebrafish larvae. Gemcitabine and paclitaxel exposure caused changes in the expression of inflammation-related, endoplasmic reticulum stress-related (ERS), and autophagy-related genes. Taken together, our findings underline that gemcitabine and paclitaxel increase developmental toxicity in zebrafish embryos in a time-dependent manner.

Internal Defense System of Mytilus galloprovincialis (Lamarck, 1819): Ecological Role of Hemocytes as Biomarkers for Thiacloprid and Benzo[a]Pyrene Pollution.

The introduction of pollutants, such as thiacloprid and benzo[a]pyrene (B[a]P), into the waters of urbanized coastal and estuarine areas through fossil fuel spills, domestic and industrial waste discharges, atmospheric inputs, and continental runoff poses a major threat to the fauna and flora of the aquatic environment and can have a significant impact on the internal defense system of invertebrates such as mussels. Using monoclonal and polyclonal anti-Toll-like receptor 2 (TLR2) and anti-inducible nitric oxide synthetase (iNOS) antibodies for the first time, this work aims to examine hemocytes in the mantle and gills of M. galloprovincialis as biomarkers of thiacloprid and B[a]P pollution and analyze their potential synergistic effect. To pursue this objective, samples were exposed to the pollutants, both individually and simultaneously. Subsequently, oxidative stress biomarkers were evaluated by enzymatic analysis, while tissue changes and the number of hemocytes in the different contaminated groups were assessed via histomorphological and immunohistochemical analyses. Our findings revealed that in comparison to a single exposure, the two pollutants together significantly elevated oxidative stress. Moreover, our data may potentially enhance knowledge on how TLR2 and iNOS work as part of the internal defense system of bivalves. This would help in creating new technologies and strategies, such as biosensors, that are more suitable for managing water pollution, and garnering new details on the condition of the marine ecosystem.

Investigation of the Impact of Point Defects in InGaN/GaN Quantum Wells with High Dislocation Densities.

In this work, we report on the efficiency of single InGaN/GaN quantum wells (QWs) grown on thin (<1 µm) GaN buffer layers on silicon (111) substrates exhibiting very high threading dislocation (TD) densities. Despite this high defect density, we show that QW emission efficiency significantly increases upon the insertion of an In-containing underlayer, whose role is to prevent the introduction of point defects during the growth of InGaN QWs. Hence, we demonstrate that point defects play a key role in limiting InGaN QW efficiency, even in samples where their density (2-3 × 109 cm-2) is much lower than that of TD (2-3 × 1010 cm-2). Time-resolved photoluminescence and cathodoluminescence studies confirm the prevalence of point defects over TDs in QW efficiency. Interestingly, TD terminations lead to the formation of independent domains for carriers, thanks to V-pits and step bunching phenomena.

Environmental Toxicity Assessment of Sodium Fluoride and Platinum-Derived Drugs Co-Exposure on Aquatic Organisms.

Pharmaceuticals are widely acknowledged to be a threat to aquatic life. Over the last two decades, the steady use of biologically active chemicals for human health has been mirrored by a rise in the leaking of these chemicals into natural environments. The aim of this work was to detect the toxicity of sodium fluoride (NaF) exposure and platinum-derived drugs in an ecological setting on aquatic organism development. From 24 to 96 h post-fertilization, zebrafish embryos were treated to dosages of NaF 10 mg/L-1 + cisplatin (CDDP) 100 µM, one with NaF 10 mg/L-1 + carboplatin (CARP) 25 µM, one with NaF 10 mg/L-1 + CDDP 100 µM + CARP 25 µM. Fluoride exposure in combination with Cisplatin and Carboplatin (non-toxic concentration) had an effect on survival and hatching rate according to this study. Additionally, it significantly disturbed the antioxidant defense system and increased ROS in zebrafish larvae. NaF 10 mg/L-1 associated with CDDP 100 µM and CARP 25 µM, increased the production of apoptosis-related proteins (caspase 3, bax, and bcl-2) and the downregulation of acetylcholinesterase (AChE) activity, while no effect was seen for the single exposure.

Environmental Co-Exposure to Potassium Perchlorate and Cd Caused Toxicity and Thyroid Endocrine Disruption in Zebrafish Embryos and Larvae (Danio rerio).

The increasing pollution of aquatic habitats with anthropogenic compounds has led to various test strategies to detect hazardous chemicals. However, information on the effects of pollutants on the thyroid system in fish, which is essential for growth, development, and parts of reproduction, is still scarce. Modified early life-stage tests were carried out with zebrafish exposed to the known thyroid inhibitor potassium perchlorate (0.1, 1, 1.5, 2, 2.5, and 5 mM) to identify adverse effects on embryo development. The endogenous antioxidant defense mechanism is one of the key functions of the thyroid gland; in this regard, we examined the co-exposure to potassium perchlorate (KClO4), which could disrupt thyroid function, with cadmium (Cd), a known pro-oxidant compound. Zebrafish embryos were exposed to control KClO4 1 mM and Cd 0.5 µM for 96 h after fertilization (hpf) individually and in combination. The morphological alteration, body length, and messenger RNA (mRNA) expression related to thyroid function and oxidative stress, thyroid hormone levels, and malondialdehyde were measured. Significant down-regulation of mRNAs related to thyroid function (thyroid hormone receptor-alpha (THRα), thyroid hormone receptor-beta (THRß), haematopoietically expressed homeobox (hhex)) and decreased thyroxin (T4) levels were observed after co-exposure to KClO4 and Cd, but this was not observed in the individually treated groups. These results suggest that co-exposure to KClO4 and Cd could affect antioxidant defense mechanisms and potentially normally increase Cd toxicity on mRNA expression, altering the thyroid functions important in zebrafish embryonic developmental stages.

Impact of Mycotoxin Contaminations on Aquatic Organisms: Toxic Effect of Aflatoxin B1 and Fumonisin B1 Mixture.

(1) Background: Multiple contaminations of several mycotoxins have been detected in human and veterinary food and feed worldwide. To date, a number of studies on the combined effects of mycotoxins have been conducted on cell and animal models, but very limited studies have been done on aquatic organisms. (2) The purpose of the present study was to evaluate the combined toxic effects of Aflatoxin B1 (AFB1) and Fumonisin B1 (FB1) on zebrafish (Danio rerio) embryos. (3) Results: Our results showed that the combination of AFB1 and FB1 at nontoxic concentrations exerted a negative effect on the lethal endpoints analyzed, such as survival, hatching, and heart rate. In addition, the mixture of mycotoxins caused an increase in the levels of enzymes and proteins involved in the antioxidant process, such as superoxide dismutase (SOD) and catalase (CAT), both in terms of protein levels and gene expression, as well as an increase in the levels of the detoxification enzymes glutathione s-transferases (GST) and cytochromes P450 (CYP450). Furthermore, we showed that the mycotoxin mixture induced an increase in pro-apoptotic proteins such as bax and caspase 3, and at the same time reduced the gene expression of the anti-apoptotic bcl-2 protein. Finally, a significant decrease in thyroid function was observed in terms of triiodothyronine (T3), thyroxine (T4), and vitellogenin (VTG) levels. (4) Conclusion: We can say that the mixture of mycotoxins carries a greater risk factor than individual presences. There is a greater need for effective detoxification methods to control and reduce the toxicity of multiple mycotoxins and reduce the toxicity of multiple mycotoxins in feed and throughout the food chain.

Toxic Exposure to Endocrine Disruptors Worsens Parkinson's Disease Progression through NRF2/HO-1 Alteration.

Human exposure to endocrine disruptors (EDs) has attracted considerable attention in recent years. Different studies showed that ED exposure may exacerbate the deterioration of the nervous system's dopaminergic capacity and cerebral inflammation, suggesting a promotion of neurodegeneration. In that regard, the aim of this research was to investigate the impact of ED exposure on the neuroinflammation and oxidative stress in an experimental model of Parkinson's disease (PD). PD was induced by intraperitoneally injections of MPTP for a total dose of 80 mg/kg for each mouse. Mice were orally exposed to EDs, starting 24 h after the first MPTP administration and continuing through seven additional days. Our results showed that ED exposure raised the loss of TH and DAT induced by the administration of MPTP, as well as increased aggregation of α-synuclein, a key marker of PD. Additionally, oral exposure to EDs induced astrocytes and microglia activation that, in turn, exacerbates oxidative stress, perturbs the Nrf2 signaling pathway and activates the cascade of MAPKs. Finally, we performed behavioral tests to demonstrate that the alterations in the dopaminergic system also reflected behavioral and cognitive alterations. Importantly, these changes are more significant after exposure to atrazine compared to other EDs. The results from our study provide evidence that exposure to EDs may play a role in the development of PD; therefore, exposure to EDs should be limited.

Toxic Effects of Endocrine Disruptor Exposure on Collagen-Induced Arthritis.

Endocrine disruptors (EDs) are chemical substances capable of affecting endocrine system functioning and interfering with organ morphogenesis and physiological functions. The development and regeneration of bone tissues have a complex hormonal regulation, and therefore, bone tissue cells can be considered potential targets for endocrine disruptors. In that regard, the aim of this research was to investigate the impact of ED exposure on the inflammatory response and oxidative stress in an experimental model of collagen-induced arthritis (CIA). Arthritis was induced by an emulsion of type II collagen (CII) and complete Freund's adjuvant, which was administered intradermally on days 0 and 21. Mice from day 21 to day 35 received the following EDs by oral gavage: cypermethrin (CP), diethyl phthalate (DEP), vinclozolin (VCZ), 17α-ethinylestradiol (EE), perfluorooctanesulfonic acid (PFOS) and atrazine (ATR). ED exposure caused worsening of clinical signs (erythema and edema in the hind paws), histological and radiographic changes, as well as behavioral deficits, induced by CII injections. Furthermore, ED exposure significantly increased the degree of inflammation and oxidative damage induced by arthritis; this upregulation was more evident after exposure to ATR than to other EDs. The results from our study suggest that exposure to EDs may play a deleterious role in the progression of RA; therefore, exposure to EDs should be limited.

Environmental Risk Assessment of Dexamethasone Sodium Phosphate and Tocilizumab Mixture in Zebrafish Early Life Stage (Danio rerio).

Pharmaceuticals are widely regarded as a menace to the aquatic environment. The constant consumption of biologically active chemicals for human health has been matched by an increase in the leaking of these compounds in natural habitats over the last two decades. This study was aimed to evaluate the molecular pathway underling the developmental toxicity of exposure in the ecological environment. Zebrafish embryos were exposed at doses of dexamethasone sodium phosphate (DEX) 1 µmol/L, tocilizumab 442.1 µmol/L and dexamethasone + tocilizumab (1 µmol/L and 442.1 µmol/L, respectively) from 24 h post-fertilization (hpf) to 96 hpf. This study confirmed that DEX exposure in association with tocilizumab 442.1 µmol/L at 1 µmol/L (non-toxic concentration) affected the survival and hatching rate, morphology score, and body length. Additionally, it significantly disturbed the antioxidant defense system in zebrafish larvae. Furthermore, a DEX 1 µmol/L and tocilizumab 442.1 µmol/L association also increased the production of apoptosis-related proteins (caspase-3, bax, and bcl-2).

Environmental Risk Assessment of Oxaliplatin Exposure on Early Life Stages of Zebrafish (Danio rerio).

Pharmaceuticals are actually identified as a threat to the ecosystem. Nowadays, the growing consumption of antineoplastic agents has been related to their continuous input in natural environments. These substances can interfere with physiological and biochemical processes of aquatic species over their entire life cycle. Oxaliplatin (OXA) is a widely used chemotherapeutic agent to treat colon or rectal cancer. This study was aimed to evaluate the developmental toxicity of the OXA exposure. To this end, zebrafish embryos were incubated with 0.001, 0.1, 0.5 mg/L OXA. At different timepoints mortality rate, hatching rate, developmental abnormalities, histological analysis, oxidative stress and mRNA expression of gene related to oxidative stress were evaluated. Our results showed that OXA exposure can induce increased mortality and developmental abnormalities reducing the hatching rate. Histological analysis demonstrated that OXA induced liver, intestine, muscle and heart injury. Superoxide dismutase and catalase activities were significantly increased after OXA exposure demonstrating its oxidative effects. The mRNA expression levels of apoptosis-related genes (caspase-3, bax and bcl-2) were significantly upregulated by OXA exposure. In conclusion, we highlighted that OXA exposure led to a dose-related developmental toxicity, oxidative stress and apoptosis.

Intestinal Disorder in Zebrafish Larvae (Danio rerio): The Protective Action of N-Palmitoylethanolamide-oxazoline.

IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis.

Assessment of 2-Pentadecyl-2-oxazoline Role on Lipopolysaccharide-Induced Inflammation on Early Stage Development of Zebrafish (Danio rerio).

Lipopolysaccharide (LPS), or bacterial endotoxin, is an important virulence factor in several human and animal pathologies. Oxazoline of Palmitoylethanolamide (PEAOXA) has shown strong anti-inflammatory activity in several animal models. LPS was applied for 24 h to zebrafish embryos to induce inflammation, and then the anti-inflammatory action of PEAOXA was evaluated for the first time in the zebrafish model (Danio rerio). Different concentrations of PEAOXA were tested for toxicity on zebrafish embryonic development; only the highest concentration of 30 mg/L showed toxic effects. Quantitative RT-PCR was applied to detect Tumor necrosis factor-α, Interleukin 1ß, 6, and 8, and members of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). Exposure to LPS induced an increase in pro-inflammatory cytokines (tumor necrosis factor and interleukin 1, 6, and 8) in both gene and protein expression, as well as an increase of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the nuclear factor kappa light polypeptide enhancer in B-cells inhibitor (IκBα) gene expression. Furthermore, acute LPS exposure also induced an increase in tryptase release, related to mast cell activity, and in the production of apoptosis-related proteins (caspase 3, bax, and bcl-2). Treatment with PEAOXA 10 mg/L significantly counteracts LPS-induced inflammation in terms of cytokine expression and decreases tryptase release and the apoptosis pathway.

Açai Berry Mitigates Vascular Dementia-Induced Neuropathological Alterations Modulating Nrf-2/Beclin1 Pathways.

The second-most common cause of dementia is vascular dementia (VaD). The majority of VaD patients experience cognitive impairment, which is brought on by oxidative stress and changes in autophagic function, which ultimately result in neuronal impairment and death. In this study, we examine a novel method for reversing VaD-induced changes brought on by açai berry supplementation in a VaD mouse model. The purpose of this study was to examine the impact of açai berries on the molecular mechanisms underlying VaD in a mouse model of the disease that was created by repeated ischemia-reperfusion (IR) of the whole bilateral carotid artery. Here, we found that açai berry was able to reduce VaD-induced behavioral alteration, as well as hippocampal death, in CA1 and CA3 regions. These effects are probably due to the modulation of nuclear factor erythroid 2-related factor 2 (Nrf-2) and Beclin-1, suggesting a possible crosstalk between these molecular pathways. In conclusion, the protective effects of açai berry could be a good supplementation in the future for the management of vascular dementia.

Actaea racemosa L. Rhizome Protect against MPTP-Induced Neurotoxicity in Mice by Modulating Oxidative Stress and Neuroinflammation.

Parkinson's disease (PD) is a dopaminergic neuron-related neurodegenerative illness. Treatments exist that alleviate symptoms but have a variety of negative effects. Recent research has revealed that oxidative stress, along with neuroinflammation, is a major factor in the course of this disease. Therefore, the aim of our study was to observe for the first time the effects of a natural compound such as Actaea racemosa L. rhizome in an in vivo model of PD induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). For the study, mice received four injections of MPTP (20 mg/kg) for the induction of PD. Starting 24 h after the first administration of MPTP we treated mice with Actaea racemosa L. rhizome (100 mg/kg) daily for seven days. Our findings clearly demonstrated that Actaea racemosa L. rhizome treatment decreases oxidative stress by activating redox balance enzymes such as Nrf2/HO-1. We also demonstrated that Actaea racemosa L. rhizome is capable of modulating inflammatory indicators involved in PD, such as IκB-α, NF-κB, GFAP and Iba1, thus reducing the degeneration of dopaminergic neurons and motor and non-motor alterations. To summarize, Actaea racemosa L. rhizome, which is subject to fewer regulations than traditional medications, could be used as a dietary supplement to improve patients' brain health and could be a promising nutraceutical choice to slow the course and symptoms of PD.