Evaluating the Role of Biochanin A in Acetic acid-Induced Colitis in Rats: Involvement of Nitric Oxide Pathway

Background and objectives: Inflammatory bowel disease (IBD) refers to idiopathic chronic and inflammatory bowel disorders such as ulcerative colitis. Considering the lack of definitive treatment and the side effects of existing drugs, finding efficient compounds is needed. Biochanin A has attracted the attention of researchers due to its wide range of medicinal activities. Until now, no study was conducted to evaluate its effects on colitis. Therefore, the aim of this study was to determine the effect of biochanin A on the nitrogen pathway in rats with acetic acid-induced colitis. Methods: Male rats were divided into five groups: normal group, negative control group, positive control group, and groups receiving biochanin A (10 and 20 mg/kg). Colitis was induced with 4% acetic acid. Next, the samples were evaluated at different macroscopic and microscopic levels, and biochemical test of superoxide dismutase (SOD) and nitric oxide activity was investigated. Results: Macroscopic and microscopic investigations showed that treatment with biochanin A decreased mucosal damage in rats with acetic acid-induced colitis. Biochanin A reduced neutrophil infiltration in the intestinal tissue. It also led to the reduction in nitric oxide and enhancement of SOD in rats. The optimal dose of biochanin A was 20 mg/kg, which had the best effect on reducing inflammation and mucosal lesions in rats. Conclusion: Biochanin A, due to its anti-inflammatory effects by reducing nitric oxide and enhancement of SOD and reducing mucosal damage in rats with acetic acid-induced colitis, can be a useful alternative drug for the prevention or treatment of IBD patients

Bioactive compounds: a goldmine for defining new strategies against pathogenic bacterial biofilms?

Most human infectious diseases are caused by microorganisms growing as biofilms. These three-dimensional self-organized communities are embedded in a dense matrix allowing microorganisms to persistently inhabit abiotic and biotic surfaces due to increased resistance to both antibiotics and effectors of the immune system. Consequently, there is an urgent need for novel strategies to control biofilm-associated infections. Natural products offer a vast array of chemical structures and possess a wide variety of biological properties; therefore, they have been and continue to be exploited in the search for potential biofilm inhibitors with a specific or multi-locus mechanism of action. This review provides an updated discussion of the major bioactive compounds isolated from several natural sources - such as plants, lichens, algae, microorganisms, animals, and humans - with the potential to inhibit biofilm formation and/or to disperse established biofilms by bacterial pathogens. Despite the very large number of bioactive products, their exact mechanism of action often remains to be clarified and, in some cases, the identity of the active molecule is still unknown. This knowledge gap should be filled thus allowing development of these products not only as novel drugs to combat bacterial biofilms, but also as antibiotic adjuvants to restore the therapeutic efficacy of current antibiotics

Correction: Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury in rats.

Correction for 'Protective effects of hydroalcoholic extracts from an ancient apple variety 'Mela Rosa dei Monti Sibillini' against renal ischemia/reperfusion injury in rats' by Hasan Yousefi-Manesh et al., Food Funct., 2019, 10, 7544–7552

Sex differences in acetylcholinesterase modulation during spatial and fear memory extinction in the amygdala; an animal study in the single prolonged stress model of PTSD

Background and purpose: Men and women show different reactions to trauma and that is believed to be the reason behind the higher prevalence of post-traumatic stress disorder (PTSD) in women. Cholinergic signaling has long been known to be involved in the processing of fear-related information and the amygdala is a critical center for fear modulation. The main goal of the current research was to find (a) whether trauma results in different learning/extinction of fear or spatial-related information among male and female rats and (b) if trauma is associated with different acetylcholinesterase (AchE) activity in the amygdala. Experimental approach: We used single prolonged stress (SPS) as a PTSD model in this study. Normal and SPS animals of both sexes were tested in contextual and spatial tasks (learning and extinction). AchE activity in the amygdala was also measured during each process. Findings / Results: Results indicated that fear and spatial learning were impaired in SPS animals. SPS animals also had deficits in fear and spatial memory extinction and the effect was significantly higher in female- SPS than in the male-SPS group. In the enzymatic tests, AchE activity was increased during the fear extinction test and incremental changes were more significant in the female-SPS group. Conclusion and implications: Collectively, these findings provided evidence that sex differences in response to trauma were at least partly related to less fear extinction potential in female subjects. It also indicated that the extinction deficit was associated with reduced cholinergic activity in the amygdala of female animals

Dapsone reduced cuprizone-induced demyelination via targeting Nrf2 and IKB in C57BL/6 mice

Objective(s): Multiple Sclerosis (MS) is an inflammatory disorder wherein the myelin of nerve cells in the central nervous system is damaged. In the current study, we assessed the effect of Dapsone (DAP) on the improvement of behavioral dysfunction and preservation of myelin in the cuprizone (CPZ) induced demyelination model via targeting Nrf2 and IKB. Materials and Methods: MS was induced in C57BL/6 mice through diet supplementation of CPZ (0.2%) for 6 weeks, and DAP (12.5 mg/kg/day; IP) was administered for the last 2 weeks of treatment. Pole test and rotarod performance test, LFB and H&E staining, and Immunohistochemistry (IHC) staining of p-Nrf2 and p-IKB were performed. Furthermore, superoxide dismutase (SOD) and nitrite were measured. Results: DAP treatment prevented body loss induced by CPZ (P<0.001). Pole test showed that CPZ increased latency time to fall (P<0.0001) but the latency to reach the floor in the DAP-CPZ group was significantly shorter (P<0.0001). Rotarod performance test showed the effect of CPZ in reducing fall time in the CPZ group (P<0.0014); however, DAP significantly increased fall time (P=0.0012). In LFB staining, DAP reduced demyelination induced by CPZ. CPZ significantly decreased p-Nrf2 and elevated p-IKB levels compared with the control group (P<0.0001), but in DAP-treated groups markedly modified these changes (P<0.0001). CPZ increased the brain nitrite levels and reduced SOD activity, but in DAP-treated considerably reversed CPZ-induced changes. Conclusion: These data support the suggestion that the beneficial properties of DAP on the CPZinduced demyelination are mediated by targeting Nrf2 and NF-kB pathways

Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations

Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-kappa B) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined

Down syndrome: Neurobiological alterations and therapeutic targets

Down syndrome (DS) is a genetic disease that occurs due to an aneuploidy of human chromosome 21. Trisomy of chromosome 21 is a primary genetic cause of developmental abnormalities leading to cognitive and learning deficits. Impairments in GABAergic transmission, noradrenergic neuronal loss, anomalous glutamatergic transmission and N-methyl-D-aspartate receptor signalling, mitochondrial dysfunction, increased oxidative stress and inflammation, differentially expressed microRNAs, increased expression of crucial chromosome 21 genes, and DNA hyper-methylation and hyperactive homocysteine trans-sulfuration pathway, are common incongruities that have been reported in DS and might contribute to cognitive impairment and intellectual disability. This review provides an update on metabolic and neurobiological alterations in DS. It also provides an overview of the currently available pharmacological therapies that may influence and/or reverse these alterations in DS

Targeting mTORs by omega-3 fatty acids: A possible novel therapeutic strategy for neurodegeneration?

Neurodegenerative diseases (NDs) such as Parkinson's (PD), Alzheimer's (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) cause significant world-wide morbidity and mortality. To date, there is no drug of cure for these, mostly age-related diseases, although approaches in delaying the pathology and/or giving patients some symptomatic relief have been adopted for the last few decades. Various studies in recent years have shown the beneficial effects of omega-3 poly unsaturated fatty acids (PUFAs) through diverse mechanisms including anti-inflammatory effects. This review now assesses the potential of this class of compounds in NDs therapy through specific action against the mammalian target of rapamycin (mTOR) signaling pathway. The role of mTOR in neurodegenerative diseases and targeted therapies by PUFAs are discussed

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity