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Recombinant interleukin-22 (rIL-22) has been reported as a protective agent in murine models of diseases driven by epithelial injury. Parasites have a circadian rhythm and their sensitivity to a certain drug may vary during the day. Therefore, this work aimed to investigate the effect of rIL-22 administration at different times of the day on the inflammation, oxidative status, and neurotransmitter release in the gut-brain axis of the Schistosoma mansoni-infected mice. Sixty male BALB/c mice aged six weeks weighing 25–30 g were divided into a control group (injected intraperitoneally with PBS), mice infected with 80 ± 10 cercariae of S. mansoni (infected group) then injected intraperitoneally with PBS, and rIL-22 treated groups. rIL-22 was administrated intraperitoneally (400 ng/kg) either at the onset or offset of the light phase for 14 days. IL-22 administration reduced the levels of IL-1β, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa beta (NF-κβ), and enhanced the production of IL-22 and IL-17. The treatment with IL-22 increased glutathione (GSH) and reduced malondialdehyde (MDA) and nitric oxide (NO) levels both in the ileum and brain. The B-cell lymphoma 2 (BCL2) protein level in the ileum was diminished after IL-22 administration. Brain-derived neurotrophic factor (BDNF) and neurotransmitter release (serotonin, 5HT, norepinephrine, NE, dopamine, DA, Glutamate, Glu, and -amino butyric acid, GABA) were improved by rIL-22. In conclusion, rIL-22 showed promising immunotherapy for inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The efficacy of IL-22 increased significantly upon its administration at the time of light offset. [ABSTRACT FROM AUTHOR]

Asiatic acid (AA) is a polyphenolic compound with potent antioxidative and anti-inflammatory activities that make it a potential choice to attenuate inflammation and oxidative insults associated with ulcerative colitis (UC). Hence, the present study aimed to evaluate if AA can attenuate molecular, biochemical, and histological alterations in the acetic acid-induced UC model in rats. To perform the study, five groups were applied, including the control, acetic acid-induced UC, UC-treated with 40 mg/kg aminosalicylate (5-ASA), UC-treated with 20 mg/kg AA, and UC-treated with 40 mg/kg AA. Levels of different markers of inflammation, oxidative stress, and apoptosis were studied along with histological approaches. The induction of UC increased the levels of lipid peroxidation (LPO) and nitric oxide (NO). Additionally, the nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant proteins [catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR)] were down-regulated in the colon tissue. Moreover, the inflammatory mediators [myeloperoxidase (MPO), monocyte chemotactic protein 1 (MCP1), prostaglandin E2 (PGE2), nuclear factor-kappa B (NF-B), tumor necrosis factor-a (TNF-a), and interleukin-1ß (IL-1ß)] were increased in the colon tissue after the induction of UC. Notably, an apoptotic response was developed, as demonstrated by the increased caspase-3 and Bax and decreased Bcl2. Interestingly, AA administration at both doses lessened the molecular, biochemical, and histopathological changes following the induction in the colon tissue of UC. In conclusion, AA could improve the antioxidative status and attenuate the inflammatory and apoptotic challenges associated with UC. [ABSTRACT FROM AUTHOR]

The aging process is characterized by circadian rhythm disruption, in physiology and behavior, which could result from weak entrainment. Light is the most potent cue that entrains the central circadian clock, which in turn synchronizes peripheral clocks in animal tissues. Period 2 (Per2) is one of the clock genes that respond to light. Moreover, oxidative stress could entrain the clock. Therefore, the present work aimed to investigate the role of light when applied late at night on the Per2, B cell lymphoma 2 (Bcl2) gene expression, and oxidative status in aged rats. Aged rats were divided into a control group and a group exposed to a 30-min light pulse applied daily during the subjective night at 5 am (ZT 22) for 4 weeks. Per2 and Bcl2 gene expression were quantified in liver tissue. To evaluate oxidative status, Glutathione (GSH), nitric oxide (NO), and malondialdehyde (MDA) were estimated. The light pulse reduced the expression levels of Per2 and Bcl2 mRNA. Although it diminished the levels of malondialdehyde (MDA), nitric oxide (NO) levels were elevated and the glutathione (GSH) levels were declined. In conclusion, the light pulse late at night abolished Per2 mRNA circadian rhythm and reduced its expression in the liver of the aged rat. Similarly, it diminished the anti-apoptotic gene expression, Bcl2. Moreover, it might attenuate oxidative stress through the reduction in MDA levels. [ABSTRACT FROM AUTHOR]

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3)‐mediated AD‐like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre‐treatment significantly decreased acetylcholinesterase activity and restored the levels of brain‐derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+/K+‐ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO‐1). Moreover, PDG exerted notable anti‐inflammatory effects via the lessening of interleukin‐1 beta, tumor necrosis factor‐alpha, cyclooxygenase‐2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro‐apoptotic (Bax and caspase‐3) levels and increases in anti‐apoptotic (Bcl‐2) biomarkers suggested an anti‐apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti‐inflammatory, and anti‐apoptotic activities of PDG establish it as a potent therapeutic option for AD. [ABSTRACT FROM AUTHOR]