Olfactory dysfunction is an early sign of neuroinflammation of the central nervous system (CNS). Microgliosis and astrogliosis are representative pathological changes that develop during ...neuroinflammation of CNS tissues. Autoimmune CNS inflammation, including human multiple sclerosis, is an occasional cause of olfactory disorders. We evaluated whether gliosis and olfactory dysfunction developed in animals with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Neuroinflammatory lesions characterized by infiltration of inflammatory cells and microglial cell activation were occasionally found in the olfactory bulbs of EAE-affected rats. Microglial activation, visualized by immunohistochemical staining of ionized calcium binding protein (Iba)-1, and astrogliosis in the olfactory bulb were also evident in the olfactory bulb of EAE rats. Inflammatory cells were found along the olfactory nerves and in the olfactory submucosa. Western blot analysis of olfactory marker protein (OMP) levels showed that OMP expression was significantly downregulated in the olfactory mucosa of EAE rats. On the buried food test, EAE-affected mice required significantly more time to find a bait pellet. Collectively, the results suggest that the olfactory dysfunction of EAE is closely linked to downregulation of OMP and the development of inflammatory foci in the olfactory system in an animal model of human multiple sclerosis.
•Periostin was constitutively detected in neurons, glial cells, and fibroblasts in CNS tissues.•Periostin was upregulated in EAE-induced spinal cords.•Periostin was detected in macrophages in the SAS ...at the early stage of EAE.•Periostin immunoreactivity was enhanced in astrocytes, microglial cells, and vascular endothelial cells in EAE.
Periostin has dual roles as a multifunctional cytokine and an extracellular matrix protein that binds to several integrins on a variety of cells. This study evaluated whether the expression and cellular localization of periostin changes in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis. Western blot analysis revealed that periostin was significantly upregulated in the spinal cord of EAE-induced mice in the effector stage, and did not significantly decrease in the recovery stage of EAE, compared with normal control. Periostin was constitutively detected in the neurons, ependymal cells, vascular endothelial cells, and astrocytes of normal mice. In the paralytic stage of EAE, periostin immunoreactivity was detected in some macrophages in the subarachnoid space (SAS), as well as in some microglial cells; in addition, periostin immunoreactivity was enhanced in astrocytes and vascular endothelial cells in EAE lesions. Collectively, these results suggest that periostin, either from monocyte-derived macrophages in SAS or glial cells in the parenchyma, partly facilitates the migration of inflammatory cells in the effector stage of EAE; moreover, periostin in the recovery stage of EAE appears to be involved in the plasticity of damaged central nervous system tissues.
Cathepsins are a family of lysosomal/endosomal proteolytic enzymes that include serine, aspartate, and cysteine proteases. The role of cathepsin in neurodegenerative diseases, including Alzheimer’s ...disease and Parkinson’s disease, remains elusive. We evaluated the expression level and localization of different cathepsins in the olfactory bulbs of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis. Quantitative real-time PCR results and Western blotting analyses revealed that serine, aspartate, and cysteine cathepsins are expressed at significantly higher levels in the olfactory bulbs of mice with EAE in the paralytic stage compared with those of control mice. Immunohistochemical analyses indicated that cathepsin A, D, and S were expressed in the glomerulus layer, external plexiform layer, and mitral cell layer. Furthermore, cathepsins were detected in astrocytes, microglia, inflammatory cells, and vascular cells in the olfactory bulb of EAE mice at the paralytic stage. Collectively, these results suggest that the upregulation of cathepsins in the olfactory bulb of mice with EAE is associated with transient olfactory dysfunction in autoimmune encephalomyelitis.
Ultraviolet B (UVB) irradiation induces skin damage and photoaging through several deleterious effects, including generation of reactive oxygen species (ROS), apoptosis of epidermal cells, ...inflammation, and collagen degradation in fibroblasts. Ergothioneine (EGT) is a naturally occurring amino acid with potential biological properties. We evaluated whether EGT protects against UVB-induced photoaging using a keratinocyte/fibroblast co-culture system. Keratinocytes were pretreated with EGT, irradiated with UVB, and co-cultured with fibroblasts. In keratinocytes, ROS production and apoptosis were assessed. We also analyzed the Nrf2/HO-1 pathway, HSP70, proapoptotic proteins, and paracrine cytokines by Western blotting and real-time PCR. Collagen degradation-related genes and senescence were also assessed in fibroblasts. EGT pretreatment of keratinocytes significantly inhibited downregulation of the Nrf2/HO-1 pathway and HSP70, and protected keratinocytes by suppressing production of ROS and cleavage of proapoptotic proteins, including caspase-8 and PARP. Furthermore, EGT significantly reduced the paracrine cytokines, including IL-1β, IL-6, and TNF-α. In co-cultures of fibroblasts with EGT-treated keratinocytes, the expression levels of collagen degradation-related genes and fibroblast senescence were significantly decreased; however, synthesis of procollagen type I was significantly increased. Our results confirm that EGT suppresses the modification of collagen homeostasis in fibroblasts by preventing downregulation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes following UVB irradiation.
EGT suppresses changes in collagen homeostasis in fibroblasts by preventing downregulation of the Nrf2/HO-1 pathway and HSP70 in keratinocytes following UVB irradiation. Display omitted
•EGT activated Nrf2/HO-1 pathway and HSP70 in UVB-irradiated keratinocytes.•EGT alleviated ROS production, apoptosis, and inflammation in UVB-irradiated keratinocytes.•EGT suppressed senescence and collagen imbalance in fibroblasts by inhibiting the keratinocyte-secreted factors.•EGT suppresses photoaging by UVB irradiation in a keratinocyte/fibroblast co-culture system.
The phenolic compounds in Lonicera japonica & Chenpi distillation extract (LCDE) were thoroughly examined for their antioxidant and anti-inflammatory properties. Phenolic compounds in LCDE were ...analyzed for five peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS) and determined. Five phenolic compounds were identified from the samples and MS data. Ultrafiltration with LC analysis was used to investigate the ability of bioactive compounds to target DPPH. As a result, it was confirmed that the major compounds exhibited a high binding affinity to DPPH and could be regarded as antioxidant-active compounds. In addition, the anti-inflammatory effect of LCDE was confirmed in vitro, and signal inhibition of anti-inflammation cytokines, MAPK and NF-kB pathways was confirmed. Finally, Molecular docking analysis supplements the anti-inflammatory effect through the binding affinity of selected compounds and inflammatory factors. In conclusion, the phenolic compounds of the LCDE were identified and potential active compounds for antioxidant and anti-inflammatory activities were identified. Additionally, this study will be utilized to provide basic information for the application of LCDE in the pharmaceutical and pharmaceutical cosmetics industries along with information on efficient screening techniques for other medicinal plants.
We evaluated the hepatoprotective activity of allyl isothiocyanate (AITC) against carbon tetrachloride (CCl4)-induced liver injury in rats. Sprague Dawley rats were orally administered AITC at doses ...of 5 (AITC 5) and 50 (AITC 50) mg/kg body weight once daily for 3 days, with or without intraperitoneal injection of CCl4. Serum chemistry was assessed for changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The enzyme activities of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were examined in liver tissues, while pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression were analyzed using real-time polymerase chain reaction. And heme oxygenase-1 (HO-1) and ionized calcium binding protein-1 (Iba-1) immunoreactivities were evaluated by Western blot analysis and immunohistochemistry, respectively. In serum chemistry, the oral administration of AITC itself did not affect the serum levels of ALT or AST, furthermore pretreatment with AITC 5 and AITC 50 significantly reduced the ALT and AST activity levels that were elevated in CCl4-intoxicated rats. In addition, AITC significantly suppressed the reduction of SOD and CAT, and the elevation of MDA, TNF-α mRNA expression, on the other hands, induced the expression of HO-1 compared with those of the vehicle-treated CCl4 group. The histopathological evaluation and Iba-1 immunoreactivity also supported the hepatoprotective effects of AITC against CCl4-induced liver injury. These results suggest that AITC ameliorates oxidative liver injury, possibly through reducing lipid peroxidation, enhancing antioxidant enzymes, and suppressing Kupffer cells and macrophages.
•AITC ameliorated the hepatotoxicity after CCl4 challenge.•AITC suppressed the activation of Kupffer cells and macrophages.•HO-1 enzyme was increased after AITC treatment.•AITC has potential to protect against oxidative stress-induced liver injury in a rat model.
Citrus species contain significant amounts of flavonoids that possess antioxidant activities; furthermore, dietary citrus is not associated with adverse effects or cytotoxicity in healthy ...individuals. Hesperidin, which is an abundant flavanone glycoside in the peel of citrus fruits, possesses a variety of biological capabilities that include antioxidant and anti-inflammatory actions. Over the last few decades, many studies have been investigated the biological actions of hesperidin and its aglycone, hesperetin, as well as their underlying mechanisms. Due to the antioxidant effects of hesperidin and its derivatives, the cardioprotective and anti-cancer effects of these compounds have been widely reviewed. Although the biological activities of hesperidin in neurodegenerative diseases have been evaluated, its potential involvement in a variety of central nervous system (CNS) disorders, including autoimmune demyelinating disease, requires further investigation in terms of the underlying mechanisms. Thus, the present review will focus on the potential role of hesperidin in diverse models of CNS neuroinflammation, including experimental autoimmune encephalomyelitis, with special consideration given to its antioxidant and anti-inflammatory effects in neurodegenerative disease models. Additionally, current evidence provides information regarding the nutraceutical use of hesperidin to prevent various CNS disorders.
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