An insight into role of amino acids as antioxidants via NRF2 activation.

Oxidative stress can affect the protein, lipids, and DNA of the cells and thus, play a crucial role in several pathophysiological conditions. It has already been established that oxidative stress has a close association with inflammation via nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway. Amino acids are notably the building block of proteins and constitute the major class of nitrogen-containing natural products of medicinal importance. They exhibit a broad spectrum of biological activities, including the ability to activate NRF2, a transcription factor that regulates endogenous antioxidant responses. Moreover, amino acids may act as synergistic antioxidants as part of our dietary supplementations. This has aroused research interest in the NRF2-inducing activity of amino acids. Interestingly, amino acids' activation of NRF2-Kelch-like ECH-associated protein 1 (KEAP1) signaling pathway exerts therapeutic effects in several diseases. Therefore, the present review will discuss the relationship between different amino acids and activation of NRF2-KEAP1 signaling pathway pinning their anti-inflammatory and antioxidant properties. We also discussed amino acids formulations and their applications as therapeutics. This will broaden the prospect of the therapeutic applications of amino acids in a myriad of inflammation and oxidative stress-related diseases. This will provide an insight for designing and developing new chemical entities as NRF2 activators.

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described.

Sublingual AKBA Exerts Antidepressant Effects in the Aß-Treated Mouse Model.

The 3-O-acetyl-11-keto-ß-boswellic acid (AKBA) is the most active compound of Boswellia serrata proposed for treating neurodegenerative disorders, including Alzheimer's disease (AD), characterized in its early phase by alteration in mood. Accordingly, we have previously demonstrated that an intracerebroventricular injection of soluble amyloid beta 1-42 (Aß) peptide evokes a depressive-like phenotype in rats. We tested the protective effects of AKBA in the mouse model of an Aß-induced depressive-like phenotype. We evaluated the depressive-like behavior by using the tail suspension test (TST) and the splash test (ST). Behavioral analyses were accompanied by neurochemical quantifications, such as glutamate (GLU), kynurenine (KYN) and monoamines, and by biochemical measurements, such as glial fibrillary acid protein (GFAP), CD11b and nuclear factor kappa B (NF-kB), in mice prefrontal cortex (PFC) and hippocampus (HIPP). AKBA prevented the depressive-like behaviors induced by Aß administration, since we recorded a reduction in latency to initiate self-care and total time spent to perform self-care in the ST and reduced time of immobility in the TST. Likewise, the increase in GLU and KYN levels in PFC and HIPP induced by the peptide injection were reverted by AKBA administration, as well as the displayed increase in levels of GFAP and NF-kB in both PFC and HIPP, but not in CD11b. Therefore, AKBA might represent a food supplement suitable as an adjuvant for therapy of depression in early-stage AD.

Effects of n-3 PUFA enriched and n-3 PUFA deficient diets in naïve and Aß-treated female rats.

Depression is one of the most common psychiatric diseases and the prevalence of depressive symptoms in women is almost twice compared to men, although the reasons of this gender difference are not fully understood yet. Recently, soluble Aß1-42 peptide has been receiving great importance in the development of depression, also since depression is highly comorbid with Alzheimer's disease and other neurodegenerative illnesses. Accordingly, we have previously shown that central Aß injection is able to elicit depressive-like phenotype in male rats. In the present study, we reproduced for the first time the Aß-induced depressive-like model in female rats, evaluating behavioural and neurochemical outcomes. Moreover, we studied the effect of lifelong exposure to either n-3 PUFA enriched or n-3 PUFA deficient diet, in female rats, both intact and after central Aß administration. Our results confirmed the Aß-induced depressive-like profile also in female rats. Moreover, chronic exposure to n-3 PUFA deficient diet led to highly negative alterations in behavioural and neurochemical parameters, while lifelong exposure to n-3 PUFA enriched diet was able to restore the Aß-induced depressive-like profile in female rats. In conclusion, the Aß-induced depressive-like profile was reversed by n-3 PUFA supplementation, indicating a possible therapeutic role of n-3 PUFA in the treatment of the burden of depressive disorders.

"Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm.

ETHNOPHARMACOLOGICAL RELEVANCE: In the South of Italy the use of herbal remedies to alleviate pregnancy-related symptoms is very common. OBJECTIVES: To investigate the proportion, prevalence of use, attitude and knowledge base in a sample of Italian pregnant women in the South of Italy. To explore the possible influence and risks of herbal consumption on pregnancy and neonatal outcomes. METHODS: A retrospective observational study was conducted during the study period November 2010-September 2013. Six hundred and thirty expectant mothers were interviewed within three days after childbirth in a public Hospital in the South of Italy. RESULTS: Due to a lack of data, a total of six hundred interviews were considered. Four hundred and eighty six women (81%) reported to have constantly used at least one herbal product throughout the pregnancy period. The study enrolled mostly women between 31 and 40 years of age, with a middle-high level of education, married and employed. The most commonly used herbal products, taken by oral route and for the entire period of pregnancy, were chamomile, fennel, propolis, cranberry, lemon balm, ginger, valerian and mallow. The most relevant source of information for the majority of participants was the doctor (95%), and most of the women (72%) informed their doctors about their use of herbal remedies. CONCLUSIONS: The regular chamomile consumption resulted in a higher risk of pre-term delivery, lower birth weight and lower length of the newborn. Also a regular use of fennel resulted in a shorter gestational age. Finally, ginger intake resulted in a shorter gestational age and in a smaller circumference of the newborn's skull.

Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.

AIMS: Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation. RESULTS: Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47(phox) were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation. INNOVATION: We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior. CONCLUSION: Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.

Clastogenicity of atrazine assessed with the Allium cepa test.

Atrazine is classified as a restricted use pesticide and it is currently included in an international revision program for re-evaluating the human and ecological (non-human populations) health risks associated with its release into the environment. The present study was undertaken to add new data on the genotoxic potential of atrazine using the Allium cepa chromosome aberration test. The test concentrations were based on the Maximum Contaminant Levels in water intended for human consumption set by European and US regulations. Atrazine produced a concentration-related increase in the number of total somatic chromosome aberrations, although this increase was statistically significant (p<0.05) only at the highest test concentration (5 microg/L). Analysis of the categories of structural chromosome damage indicated that breaks were the predominant lesion induced; the percent of cells per bulb with breaks also increased in a concentration-related manner, and the increase was statistically significant at the two highest test concentrations (1 and 5 microg/L) (p<0.05). The Allium cepa plant assay detected the clastogenicity of atrazine at concentrations that are likely to be encountered in water, a common site of atrazine contamination.