The preventive effects of Saccharomyces boulardii against oxidative stress induced by lipopolysaccharide in rat brain.

The brain is sensitive to oxidative stress, which can trigger microglial activation and neuroinflammation. Antioxidant therapies may provide neuroprotection against oxidative stress. In recent years antioxidant effects of probiotics and their possible mechanisms in oxidative stress-related models have been determined. In the current study, for the first time, we assessed the effects of Saccharomyces boulardii on oxidative stress provoked by lipopolysaccharide (LPS) in the rat brain. Four groups of animals were used, including the control, LPS, S. boulardii + LPS, and S. boulardii groups. All animals received either saline or S. boulardii (1010 CFU) by gavage for four weeks. Between days 14 and 22, all animals received either LPS (250 µg/kg) or saline by intraperitoneal (i.p.) injection. S. boulardii was able to inhibit lipid peroxidation and prevent the reduction of antioxidant levels, including glutathione and catalase in the model of oxidative stress induced by LPS in the rat hippocampus and cortex. Also, it increased the lowered ratio of glutathione/oxidized glutathione in both tissues. Serum levels of anti-inflammatory interleukin 10 (IL-10) and proinflammatory cytokines IL-6 and IL-8 increased and decreased, respectively. S. boulardii has potential antioxidant activities in oxidative stress-related model, possibly modulating gut microbiota, immune defense, and antioxidant enzyme activities that can be considered in preventing oxidative stress-related central nervous system (CNS) diseases.

Can nonsteroidal anti-inflammatory drugs (NSAIDs) be repurposed for fungal infection?

Nonsteroidal anti-inflammatory drugs (NSAIDs) are an important class of anti-inflammatory drugs widely used for the treatment of musculoskeletal disorders, mild-to-moderate pain, and fever. This review aimed to explain the functional role and possible mechanisms of the antifungal effects of NSAIDs alone or in combination with antifungal drugs in vitro and in vivo. Several studies reported that NSAIDs such as aspirin, ibuprofen, diclofenac, indomethacin, ketorolac, celecoxib, flurbiprofen, and nimesulide had antifungal activities in vitro, either fungistatic or fungicidal, against different strains of Candida, Aspergillus, Cryptococcus, Microsporum, and Trichophyton species. These drugs inhibited biofilm adhesion and development, and yeast-to-hypha conversion which may be related to a prostaglandin E2 (PGE2)/PGEx-dependent mechanism. Modulating PGE2 levels by NSAIDs during fungal infection can be introduced as a possible mechanism to overcome. In addition, some important mechanisms of the antifungal activities of NSAIDs and their new derivatives on fungi and host immune responses are summarized. Overall, we believe that using NSAIDs along with classical antifungal drugs has the potential to be investigated as a novel therapeutic strategy in clinical studies. Furthermore, combination therapy can help manage resistant strains, increase the efficacy of antifungal drugs, and reduce toxicity.

Short chain fatty acids, a possible treatment option for autoimmune diseases.

Gut microbiota can interact with the immune system through its metabolites. Short-chain fatty acids (SCFAs), as one of the most abundant metabolites of the resident gut microbiota play an important role in this crosstalk. SCFAs (acetate, propionate, and butyrate) regulate nearly every type of immune cell in the gut's immune cell repertoire regarding their development and function. SCFAs work through several pathways to impose protection towards colonic health and against local or systemic inflammation. Additionally, SCFAs play a role in the regulation of immune or non-immune pathways that can slow the development of autoimmunity either systematically or in situ. The present study aims to summarize the current knowledge on the immunomodulatory roles of SCFAs and the association between the SCFAs and autoimmune disorders such as celiac disease (CD), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), type 1 diabetes (T1D) and other immune-mediated diseases, uncovering a brand-new therapeutic possibility to prevent or treat autoimmunity.

Preventive Effect of Saccharomyces boulardii on Memory Impairment Induced by Lipopolysaccharide in Rats.

Recent studies have indicated that dysfunction of gut microbiota, living microorganisms of the digestive tract, plays a role in the pathogenesis of neurodegenerative disorders, indicating the valuable impact of probiotics as a potential preventive or therapeutic strategy. Saccharomyces boulardii is a yeast probiotic with beneficial effects on various disorders, ranging from inflammatory gastrointestinal diseases to brain and behavioral disorders. Herein, we examined the effect of S. boulardii on memory impairment induced by lipopolysaccharide (LPS) in Wistar rats. Four groups of rats were used in this study (N = 10): (1) control [Cnt], (2) LPS, (3) LPS + S. boulardii [LPS + S], and (4) S. boulardii [S]. Animals were orally administered S. boulardii (250 mg/rat) or saline by gavage for 4 weeks. From the 14th day of the study, animals were administered intraperitoneal LPS (0.25 mg/kg/day) or saline for 9 days. We assessed memory impairment, neuroinflammation, and amyloid-ß deposition. S. boulardii ameliorated LPS-induced memory dysfunction. We observed that S. boulardii significantly reduced the elevated levels of serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, as well as hippocampal levels of NLRP3 and caspase-1 in the LPS model. Moreover, S. boulardii alleviated amyloid-ß deposition in the rat hippocampus. Collectively, our findings indicated that S. boulardii could inhibit memory impairment, neuroinflammation, and amyloid-ß accumulation induced by LPS, possibly by modifying the gut microbiota.

Interaction of Medicinal Plants and Their Active Constituents With Potassium Ion Channels: A Systematic Review.

Potassium ion (K+) channels are pore-forming transmembrane proteins that control the transport of K+ ions. Medicinal plants are widely used as complementary therapies for several disorders. Studies have shown that the modulation of K+ channels is most likely involved in various pharmacological effects of medicinal plants. This review aimed to evaluate the modulatory effects of medicinal plants and their active constituents on K+ channels under pathological conditions. This systematic review was prepared according to the Preferred Reporting Items for the Systematic Reviews and Meta-analyses (PRISMA) 2020 guideline. Four databases, including PubMed, Web of Science, embase, and Scopus, were searched. We identified 687 studies from these databases, from which we selected 13 in vivo studies for the review by using the Population, Intervention, Comparison, Outcomes, Study (PICOS) tool. The results of the 13 selected studies showed a modulatory effect of medicinal plants or their active constituents on ATP-sensitive potassium channels (KATP), and small (SKCa) and large (BKCa) conductance calcium-activated K+ channels in several pathological conditions such as nociception, brain ischemia, seizure, diabetes, gastric ulcer, myocardial ischemia-reperfusion, and hypertension via possible involvement of the nitric oxide/cyclic GMP pathway and protein kinase. K+ channels should be considered as significant therapeutic milestones in the treatment of several diseases. We believe that understanding the mechanism behind the interaction of medicinal plants with K+ channels can facilitate drug development for the treatment of various K+ channel-related disorders.

Saccharomyces boulardii attenuates lipopolysaccharide-induced anxiety-like behaviors in rats.

Anxiety is the brain's response to dangerous or stressful situations. Exposure to stressors can cause gut microbiota dysbiosis and activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to the secretion of glucocorticoids associated with anxiety. Recent studies have reported that probiotics can attenuate anxiety-like behaviors by modulation of the gut microbiome composition. The present study aimed to investigate the effects of Saccharomyces boulardii (Sb) administration on anxiety-like behaviors induced by lipopolysaccharide (LPS) in rats. The animals were randomly divided into four groups (Control, LPS, Sb + LPS, and Sb). All animals were orally treated with saline or S. boulardii (1010 CFU/ml/rat) for 28 days. They were also injected with saline or LPS (250 µg/kg/day) intraperitoneally from day 14 until day 22. Anxiety-like behaviors were assessed using the elevated plus-maze and open-field tests. Besides, the serum levels of cortisol, corticosterone, serotonin, and brain-derived neurotrophic factor (BDNF) were measured. The results revealed that S. boulardii could attenuate LPS-induced anxiety-like behaviors. The findings also showed that oral administration of S. boulardii significantly attenuated the elevated levels of cortisol and corticosterone in the LPS-induced model. Moreover, S. boulardii alleviated the decremental effect of LPS on the serum serotonin and BDNF levels. According to the present findings, S. boulardii can prevent LPS-induced anxiety-like behaviors, probably through modulation of the HPA axis and the gut microbiome.

Review of registered clinical trials for the treatment of COVID-19.

Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease was first reported in December 2019 in Wuhan, China, but now more than 200 countries have been affected and the coronavirus pandemic is still ongoing. The severity of COVID-19 symptoms can range from mild to severe. FDA approved remdesivir as a treatment of COVID-19 so far. Various clinical trials are underway to find an effective method to treat patients with COVID-19. This review aimed at summarizing 219 registered clinical trials in the ClinicalTrials.gov database with possible mechanisms, and novel findings of them, and other recent publications related to COVID-19. According to our analyses, various treatment approaches and drugs are being investigated to find an effective drug to cure COVID-19 and among all strategies, three important mechanisms are suggested to be important against COVID-19 including antiviral, anti-inflammatory, and immunomodulatory properties. Our review can help future studies get on the way to finding an effective drug for COVID-19 treatment by providing ideas for similar researches.

Review of the effects of vitexin in oxidative stress-related diseases.

Vitexin is an apigenin flavone glycoside found in food and medicinal plants. It has a variety of pharmacological effects, including antioxidant, anti-inflammatory, anticancer, antinociceptive, and neuroprotective effects. This review study summarizes all the protective effects of vitexin as an antioxidant against reactive oxygen species, lipid peroxidation, and other oxidative damages in a variety of oxidative stress-related diseases, including seizure, memory impairment, cerebral ischemia, neurotoxicity, myocardial and respiratory injury, and metabolic dysfunction, with possible molecular and cellular mechanisms. This review describes any activation or inhibition of the signaling pathways that depend on the antioxidant activity of vitexin. More basic research is needed on the antioxidative effects of vitexin in vivo, and carrying out clinical trials for the treatment of oxidative stress-related diseases is also recommended.

Quercetin in Food: Possible Mechanisms of Its Effect on Memory.

Quercetin (3,3',4',5,7-pentahydroxyflavone) is found in vegetables and fruits. It is one of the major flavonoids that is part of human diets. Quercetin has several pharmacological effects in the nervous system as a neuroprotective agent. In this review, we summarize the research on quercetin and its role in memory in both animals and humans. Articles were chosen from the Scopus, PubMed, and Web of Science databases. In this review, we describe and summarize the importance of quercetin's presence in the body, particularly in the brain; its kinetics, including its absorption, metabolism, distribution, and excretion; its behavioral effects; and some of the possible mechanisms of action of quercetin on memory in different animal models. Several important pathways that may be involved in the processes of learning and memory, long-term potentiation, and cognition may be impaired during neurological diseases or other medical conditions. As dietary quercetin is important, provision of its best formulation for delivery to the brain as a nutraceutical and in clinical translational research for the prevention or treatment of Alzheimer's disease and other types of dementia is necessary.

Correlation of micro vessel density and c-Myc expression in breast tumor of mice following mesenchymal stem cell therapy.

Stem cell therapy for degenerative diseases has been established; however there are controversies over the treatment of solid tumors with stem cell transplantation. In the present study, the anti-tumor action of mesenchymal stem cells (MSCs) has been examined in a mouse model of breast cancer with emphasize on tumor growth, angiogenesis and c-Myc expression in breast tumors. For this purpose, MSCs were isolated from bone marrow of Balb/c mice and characterized. A Balb/c mouse model of breast cancer was developed and subjected to cell therapy intra venous (I.V) or intra tumor (I.T) with MSCs. Tumor growth was measured using a digital caliber for until the end of experiment (30days). Then the mice were sacrificed and their tumors were removed and processed for histopathological examination, immunohistochemical assay of CD31 and measuring of c-Myc expression using quantitative PCR. Detection of the labeled-MSCs in tumors following injection of the cells (I.V or I.T) clearly showed the homing of MSCs into tumors. Tumor growth in case of MSC-treated mice by I.V and I.T routes was inhibited by approximately 28% and 34% respectively compared to controls. The suppression of angiogenesis was reflected in Micro Vessel Density (MVD) following I.V or I.T delivery of the MSCs. c-Myc gene expression in tumor tissues of mice treated I.V or IT with MSCs was down-regulated to 28.0% and 16.0% respectively compare to control groups. In conclusion, growth inhibition of breast tumors in mice due to MSC therapy is associated with modulation of c-Myc activation and angiogenesis markers.