Edaravone Dexborneol Alleviates Neuroinflammation by Reducing Neuroglial Cell Proliferation and Suppresses Neuronal Apoptosis/Autophagy in Vascular Dementia Rats.

More and more evidence shows that the pathological mechanism of vascular dementia (VD) is closely related to oxidative stress injury, cell apoptosis, autophagy, inflammatory response, excitatory amino acid toxicity, synaptic plasticity change, calcium overload, and other processes. Edaravone dexborneol (EDB) is a new type of neuroprotective agent that can improve the neurological damage caused by an ischemic stroke. Previous studies showed that EDB has effects on synergistic antioxidants and induces anti-apoptotic responses. However, it remains unclear whether EDB can affect apoptosis and autophagy by activating the PI3K/Akt/mTOR signaling pathway and its impact on the neuroglial cells. In this study, we established the VD model of rats by bilateral carotid artery occlusion to explore the neuroprotective effect of EDB and its mechanism. Morris Water Maze test was applied to assess the cognitive function of rats. H&E and TUNEL staining were applied to observe the cellular structure of the hippocampus. Immunofluorescence labeling was used to observe the proliferation of astrocytes and microglia. ELISA was applied to examine the levels of TNF-α, IL-1ß and IL-6, and RT-PCR was applied to examine their mRNA expression levels. Western blotting was applied to examine apoptosis-related proteins (Bax, Bcl-2, Caspase-3), autophagy-related proteins (Beclin-1, P62, LC3B), PI3K/Akt/mTOR signaling pathway proteins and their phosphorylation levels. The results indicated that EDB ameliorates learning and memory in rats subjected to the VD model, alleviates neuroinflammatory response by reducing the proliferation of the neuroglial cell and inhibits apoptosis and autophagy, which may be mediated by the PI3K/Akt/mTOR signaling pathway.

The combination of exercise and metformin inhibits TGF-ß1/Smad pathway to attenuate myocardial fibrosis in db/db mice by reducing NF-κB-mediated inflammatory response.

Persistent hyperglycemia increases inflammation response, promoting the development of myocardial fibrosis. Based on our previous research that exercise and metformin alone or their combination intervention could attenuate myocardial fibrosis in db/db mice, this study aimed to further explore the underlying mechanisms by which these interventions attenuate myocardial fibrosis in early diabetic cardiomyopathy. Forty BKS db/db mice were randomly divided into four groups. Diabetic db/db mice without intervention were in the C group. Aerobic exercise (7-12 m/min, 30-40 min/day, 5 days/week) was performed in the E group. Metformin (300 mg·kg-1·day-1) was administered in the M group. Exercise combined with metformin was performed in the EM group. Ten wild-type mice were in the WT group. All interventions were administered for 8 weeks. Results showed that the expression levels of α-SMA, Collagen I, and Collagen III were increased in 16-week-old db/db mice, which were reversed by exercise and metformin alone or their combination intervention. All interventions attenuated the level of TGF-ß1/Smad2/3 pathway-related proteins and reduced the expression of inflammatory signaling pathway-regulated proteins TNF-α, p-IκBα/IκBα, and p-NF-κB p65/NF-κB p65 in db/db mice. Furthermore, metformin intervention inhibited HNF4α expression via AMPK activation, whereas exercise intervention increased the expression of IL-6 instead of activating AMPK. In conclusion, exercise and metformin alone or their combination intervention inhibited the TGF-ß1/Smad pathway to attenuate myocardial fibrosis by reducing NF-κB-mediated inflammatory response. The anti-fibrotic effects were regulated by metformin-activated AMPK or exercise-induced elevation of IL-6, whereas their combination intervention showed no synergistic effects.

Resveratrol reduces inflammatory response and detrimental effects in chronic cerebral hypoperfusion by down-regulating stimulator of interferon genes/TANK-binding kinase 1/interferon regulatory factor 3 signaling.

Inflammatory responses induced by chronic cerebral hypoperfusion (CCH) play a critical role in the progression of vascular dementia. Stimulator of interferon genes (STING) signaling function as a key mediator of inflammation and immunological responses in the central nervous system (CNS), and resveratrol (RES) exerts potent anti-inflammatory effects. However, the role of STING signaling and the relationship between RES and STING signaling in persistent hypoperfusion-induced cerebral inflammation remain unclear. In this study, Sprague-Dawley rats were subjected to either Sham or bilateral common carotid artery occlusion (2VO) surgery and received RES or vehicle daily by intraperitoneal injection for 4 or 8 weeks. Morris's water maze was used for the analysis of cognitive function. The neuroinflammatory responses in white matter and hippocampus of the rat brain were assessed by Western blot, Immunofluorescence staining, and qRT-PCR analyses. Myelin integrity, neutrophil infiltration, and microglia proliferation were assessed by Immunohistochemistry and histologic analysis. We demonstrated that after CCH, neurons, microglia, and astrocyte under endoplasmic reticulum (ER) stress upregulated the expression of STING, TANK-binding kinase 1 (TBK1), and the transcription factor interferon regulatory factor 3 (IRF3), as well as translocation of IRF3 into the nucleus. These were accompanied by infiltration of neutrophils, activation of microglia, and overproduction of proinflammatory mediators. Improvements in cognitive deficits were related to reduced hippocampal neuronal cell death and increased myelin integrity in RES-treated rats. The neuroprotective effects of RES were associated with suppression of the expression of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), VCAM-1, interferon-ß (IFN-ß), and IL-1ß, likely through mitigation of the STING/TBK1/IRF3 pathway. These inhibitory effects exerted by RES also inhibited the levels of myeloperoxidase, reduced excess expression of reactive astrocytes, and activated microglia. In conclusion, the STING/TBK1/IRF3 axis may be critical for proinflammatory responses in cerebral tissue with persistent hypoperfusion, and RES exerts its anti-inflammatory effects by suppressing STING/TBK1/IRF3 signaling.

Role of the dietary components in food allergy: A comprehensive review.

Currently, the increasing incidence of food allergy is considered a major public health and food safety concern. Importantly, food-induced anaphylaxis is an acute, life-threatening, systemic reaction with varied clinical presentations and severity that results from the release of mediators from mast cells and basophils. Many factors are blamed for the increasing incidence of food allergy, including hygiene, microbiota (composition and diversity), inopportune complementary foods (a high-fat diet), and increasing processed food consumption. Studies have shown that different food components, including lipids, sugars, polyphenols, and vitamins, can modify the immunostimulating properties of allergenic proteins and change their bioavailability. Understanding the role of the food components in allergy might improve diagnosis, treatment, and prevention of food allergy. This review considers the role of the dietary components, including lipids, sugars, polyphenols, and vitamins, in the development of food allergy as well as results of mechanistic investigations in in vivo and in vitro models.

DL-3-n-butylphthalide suppressed autophagy and promoted angiogenesis in rats with vascular dementia by activating the Shh/Ptch1 signaling pathway.

DL-3-n-butylphthalide (NBP) has neuroprotective effect on chronic cerebral hypoperfusion animals. Here, we explored the role and underlying mechanism of NBP on autophagy and angiogenesis in rats with vascular dementia (VD). Adult male Sprague-Dawley (SD) rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to establish VD model. These rats were randomly divided into five groups: sham, model, NBP120 (120 mg/kg), Shh siRNA (50 nM), and NBP120 + Shh siRNA groups. Our results showed that NBP treatment attenuated memory damage in rats with VD, as demonstrated by Morris water maze tests. Immunofluorescence (IF) assay revealed that NBP induced neuronal process length and neuronal activity in hippocampus, which were reversed by Shh silencing. Furthermore, NBP treatment also reduced the expression of autophagy marker proteins B-cell lymphoma-2 interacting protein 1 (Beclin 1) and microtubule-associated protein 1 light chain 3 (LC3), which were further enhanced by Shh silencing. Meanwhile, NBP promoted the angiogenesis, which was accompanied by upregulated vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-1, and Angiopoietin (Ang) expression in the hippocampus. And Shh siRNA co-treatment blocked the angiogenesis induced by NBP. Altogether, our results established that NBP treatment suppressed autophagy and improved angiogenesis and neurobehavioral recovery in VD rats partly by activating the Shh/Ptch1 signaling pathway.