Alleviation Of Inflammatory Response Research Articles

Piperlongumine alleviates corneal allograft rejection via suppressing angiogenesis and inflammation.

Neovascularization and inflammatory response are two essential features of corneal allograft rejection. Here, we investigated the impact of Piperlongumine (PL) on alleviating corneal allograft rejection, primarily focusing on pathological angiogenesis and inflammation. A murine corneal allograft transplantation model was utilized to investigate the role of PL in preventing corneal allograft rejection. PL (10 mg/kg) or vehicle was intraperitoneally injected daily into BALB/c recipients from day -3 to day 14. The clinical signs of the corneal grafts were monitored for 30 days. Corneal neovascularization and inflammatory cell infiltration were detected by immunofluorescence staining and immunohistochemistry. The proportion of CD4+ T cells and macrophages in the draining lymph nodes (DLNs) was examined by flow cytometry. In vitro, HUVECs were cultured under hypoxia or incubated with TNF-α to mimic the hypoxic and inflammatory microenvironment favoring neovascularization in corneal allograft rejection. Multiple angiogenic processes including proliferation, migration, invasion and tube formation of HUVECs in hypoxia with or without PL treatment were routinely evaluated. The influence of PL treatment on TNF-α-induced pro-inflammation in HUVECs was investigated by real-time PCR and ELISA. In vivo, PL treatment effectively attenuated corneal allograft rejection, paralleled by coincident suppression of neovascularization and alleviation of inflammatory response. In vitro, PL distinctively inhibited hypoxia-induced angiogenic processes in HUVECs. Two key players in hypoxia-induced angiogenesis, HIF-1α and VEGF-A were significantly suppressed by PL treatment. Also, TNF-α-induced pro-inflammation in HUVECs was hampered by PL treatment, along with a pronounced reduction in ICAM-1, VCAM-1, CCL2, and CXCL5 expression. The current study demonstrated that PL could exhibit both anti-angiogenic and anti-inflammatory effects in preventing corneal allograft rejection, highlighting the potential therapeutic applications of PL in clinical strategy.

Vitamin E reduces inflammation and improves cognitive disorder and vascular endothelial functions in patients with leukoaraiosis

Background Leukoaraiosis (LA) is a disease manifested by demyelination and gliosis in white matter, mainly caused by cerebrovascular diseases. LA is closely related to the expression level of inflammatory factors, oxidative stress, and vascular endothelial dysfunction in patients. Vitamin E may play antioxidant and anti-inflammatory roles in various diseases. We aimed to explore the effects of vitamin E on the patients with LA. Methods A total of 160 patients with LA were recruited in this research. Matrix metalloproteinase-9 (MMP-9), MMP-2, C-reactive protein (CRP), complement 3 (C3), C4, nitric oxide (NO), and endothelin (ET) levels were evaluated by ELISA. The Mini-Mental State Examination (MMSE) was used for cognitive impairment assessment. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were analyzed by commercial kits. Results The levels of CRP, C3, and C4 significantly decreased in the serum of LA patients after the administration of vitamin E. The levels of MMP-2 and MPP-9 showed a significant decrease in the administered group. Vitamin E significantly inhibited the expression of MDA, while significantly upregulated the expression of SOD. Significant increase in NO production and significant downregulation of ET expression occurred in vitamin E groups. MMSE score was significantly increased by vitamin E. Conclusion In conclusion, vitamin E showed effects on the alleviation of inflammatory response, oxidative stress, endothelial damage, and cognitive dysfunction. Thus, vitamin E could be a potential drug for the clinical treatment of LA patients.

ACT001 attenuates microglia-mediated neuroinflammation after traumatic brain injury via inhibiting AKT/NF\u03baB/NLRP3 pathway

BackgroundMicroglia-mediated neuroinflammatory response following traumatic brain injury (TBI) is considered as a vital secondary injury factor, which drives trauma-induced neurodegeneration and is lack of efficient treatment. ACT001, a sesquiterpene lactone derivative, is reportedly involved in alleviation of inflammatory response. However, little is known regarding its function in regulating innate immune response of central nervous system (CNS) after TBI. This study aimed to investigate the role and underlying mechanism of ACT001 in TBI.MethodsControlled cortical impact (CCI) models were used to establish model of TBI. Cresyl violet staining, evans blue extravasation, neurobehavioral function assessments, immunofluorescence and transmission electron microscopy were used to evaluate therapeutic effects of ACT001 in vivo. Microglial depletion was induced by administering mice with colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. Cell-cell interaction models were established as co-culture system to simulate TBI conditions in vitro. Cytotoxic effect of ACT001 on cell viability was assessed by cell counting kit-8 and activation of microglia cells were induced by Lipopolysaccharides (LPS). Pro-inflammatory cytokines expression was determined by Real-time PCR and nitric oxide production. Apoptotic cells were detected by TUNEL and flow cytometry assays. Tube formation was performed to evaluate cellular angiogenic ability. ELISA and western blot experiments were used to determine proteins expression. Pull-down assay was used to analyze proteins that bound ACT001.ResultsACT001 relieved the extent of blood-brain barrier integrity damage and alleviated motor function deficits after TBI via reducing trauma-induced activation of microglia cells. Delayed depletion of microglia with PLX5622 hindered therapeutic effect of ACT001. Furthermore, ACT001 alleviated LPS-induced activation in mouse and rat primary microglia cells. Besides, ACT001 was effective in suppressing LPS-induced pro-inflammatory cytokines production in BV2 cells, resulting in reduction of neuronal apoptosis in HT22 cells and improvement of tube formation in bEnd.3 cells. Mechanism by which ACT001 functioned was related to AKT/NFκB/NLRP3 pathway. ACT001 restrained NFκB nuclear translocation in microglia cells through inhibiting AKT phosphorylation, resulting in decrease of NLRP3 inflammasome activation, and finally down-regulated microglial neuroinflammatory response.ConclusionsOur study indicated that ACT001 played critical role in microglia-mediated neuroinflammatory response and might be a novel potential chemotherapeutic drug for TBI.FQdKbSYTeaAq3ny7ETc-jcVideo

The Nutritional Properties, Chemical Compositions, and Functional Characteristics of the Aerial Parts of Adonis coerulea.

The nutrition and active compounds from plants are very important to regulate the immunity of the body by improving the oxidant and inflammatory response. In this article, we aimed to investigate the nutritional profile and the phytochemical compositions of Adonis coerulea; the functional characteristics and its possible mechanism were studied. Results showed that the aerial parts of Adonis coerulea (ACAP) contained the abundant of proteins (16.15%) and the minerals (31.02.09 mg/100 g dried ACAP); promisingly, the content of essential amino acids (8.25%) and fatty acids (13,220.45 mg/100 g) also were obtained to regulate the immunity and prevent some chronic diseases. The methanol extract of ACAP played the anti-inflammatory activity via peroxisome proliferators-activated receptor (PPAR)-γ-mediated nuclear factor kappa B (NF-κB) pathway. Among the 18 identified compounds, linolenic acid from fatty acids and licochalcone A were active compounds by inhibiting nitric oxide (NO) production of RAW264.7 cells induced by lipopolysaccharide (LPS). The alleviation of inflammatory response results in the decrease of oxidative stress; ACAP showed the antioxidant activity by attenuating antioxidant enzymes, improving mitochondrial membrane potential and reactive oxygen species. These results highlight the potential of A. coerulea as a source of active ingredients in pharmaceutical industries.

Micheliolide alleviates ankylosing spondylitis (AS) by suppressing the activation of the NLRP3 inflammasome and maintaining the balance of Th1/Th2 via regulating the NF-κB signaling pathway.

BackgroundAnkylosing spondylitis (AS) is a common form of inflammatory arthritis. Micheliolide (MCL), a sesquiterpene lactone, is reportedly involved in the alleviation of inflammatory response. This study aimed to investigate the mechanism of MCL in the treatment of AS.MethodsMice were randomly divided into five groups: the sham group, the MCL (50 mg/kg) group, the AS model group, the AS + MCL (20 mg/kg) group, and the AS + MCL (50 mg/kg) group. After the addition of the inhibitor celastrol, mice were randomly divided into five groups: the sham group, the AS model group, the AS + MCL (50 mg/kg) group, the AS + Celastrol (1 mg/kg) group, and the AS + Celastrol (1 mg/kg) + MCL (50 mg/kg) group.ResultsCompared with the AS model mice, the protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18 were decreased after MCL treatment. The protein expression levels of capase-1 p10, IL-1β p17, NOD-like receptor family and pyrin domain containing 3 (NLRP3), caspase-1, and apoptosis-associated speck-like protein (ASC) were also reduced. The protein expression levels of Interferon (IFN)-γ were down-regulated, but levels of IL-4 were increased. Western blotting and immunohistochemistry revealed that the levels of p-IκB α were up-regulated, while the levels of phosphorylated-p65 were down-regulated. After the addition of celastrol, MCL treatment significantly reduced the levels of p-p65, NLRP3, caspase-1, and ASC. Meanwhile, the levels of IFN-γ were markedly down-regulated, but the levels of IL-4 were enhanced.ConclusionsOur study found that MCL suppressed the activation of NLRP3 inflammasome and maintained the balance of Th1/Th2 via regulating NF-κB signaling. Therefore, MCL could potentially be used to treat AS.

Anti-inflammatory effect and potential mechanism of betulinic acid on λ-carrageenan-induced paw edema in mice

λ-Carrageenan (Carr), a seaweed polysaccharide, is used as a proinflammatory agent in research. Betulinic acid (BA), a naturally occurring pentacyclic triterpenoid, exerts immunomodulatory, antioxidant, anti-inflammatory, antitumor, anti-malarial and anti-HIV effects. The aim of this study was to investigate whether BA exerts anti-inflammatory effect against Carr-induced paw edema in mice, and how BA could mediate the expression of inflammation-associated MAPK-COX-2-PGE2 signal pathway. BA pretreatment significantly reduced the inflammatory response to Carr-induced paw edema, especially at 4 h after injection. BA reduced the serum levels of pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-5, IL-6, GM-CSF, KC, MCP-1 and PGE2 in Carr-treated mice, and increased those of anti-inflammatory cytokines, such as IL-12. It also increased SOD, CAT and GSH-Px activities, and GSH content, and reduced MDA content in the liver of Carr-treated mice. Besides, BA reduced neutrophil infiltration in the basal and subcutaneous layers of the paw of Carr-treated mice, decreased the expression of COX-2 protein, and reduced the phosphorylation of JNK, p38 and ERK1/2. These results indicated that the protective effect of BA on Carr-induced paw edema might be due to its alleviation of inflammatory response and inhibition of oxidative stress, possibly by inhibiting MAPK-COX-2-PGE2 signaling pathway activation.

Biodegradable Magnesium-Incorporated Poly(l-lactic acid) Microspheres for Manipulation of Drug Release and Alleviation of Inflammatory Response.

Poly(l-lactic acid) (PLLA) and magnesium (Mg) are widely concerned biodegradable materials, but during in vivo implantation, the former produces acidic degradation byproducts and can easily induce inflammation in surrounding tissues, whereas the latter is fast corroded and generates alkaline products. The purpose of this study is to develop Mg/PLLA composite microspheres as a novel delivery system, in which Mg particles are used to regulate the drug release profile and suppress PLLA-induced inflammatory response. Morphological observation shows that multiple Mg particles are dispersed both on the surface and in the interior of composite microspheres. In vitro release study indicates that by varying the Mg contents or its particle sizes, the internal connectivity of composite microspheres is changed during hydrolytic degradation, and drug delivery can be facilely manipulated with tunable release patterns. In vivo release study further confirms the feasibility of Mg/PLLA microspheres for tailoring drug release in a physiological environment. The animal experiment reveals that Mg particles can alleviate macrophage infiltration and inflammatory cytokine expression. These results demonstrate the availability of using biodegradable Mg particles to manipulate drug release as well as alleviate PLLA-induced inflammation. The present Mg/PLLA composite microspheres have potential applications in controlled delivery of various therapeutic agents, especially some growth factors, for bone regeneration.

TRUSS inhibition protects against high fat diet (HFD)-stimulated brain injury by alleviation of inflammatory response

High fat diet (HFD)-induced obesity is associated with insulin resistance (IR) and other chronic, diet associated illnesses, including neuroinflammation and brain injury. However, the involvement of inflammatory response in HFD-elicited central nerve injury has yet to be fully determined. Recent studies have indicated that tumor necrosis factor receptor-associated ubiquitous scaffolding and signaling protein (TRUSS), also known as TRPC4AP, plays an essential role in regulating inflammation via the meditation of NF-κB signaling. In the present study, we attempted to explore the effects of TRUSS on HFD-induced brain injury in the wild type mice (TRUSS+/+) or TRUSS-knockout mice (TRUSS−/-). The results suggested that TRUSS deletion attenuated HFD-induced cognitive impairments in mice. HFD-elicited metabolic disorders were also highly improved by the loss of TRUSS, as evidenced by the reduced serum glucose and insulin levels, as well as the lipid deposition in liver tissues. In addition, HFD-triggered brain injury was markedly alleviated by the TRUSS ablation, as proved by the reduction of GFAP and Iba1 expressions in hippocampus and hypothalamus. Moreover, TRUSS−/- mice exhibited a significant decrease in the expression of pro-inflammatory cytokines, accompanied with the inactivation of IKKα/IκBα/NF-κB pathway. At the same time, HFD-induced dyslipidemia was also alleviated by the loss of TRUSS. The in vitro study verified the protective effects of TRUSS-suppression against HFD-induced central nerve injury and hepatic steatosis by restraining the inflammatory response. In summary, our data indicated that TRUSS participated in metabolic syndrome-induced brain injury and pointed to the repression of TRUSS as a promising strategy for cognitive deficits therapy.

Mesenchymal stem cells in skin wound healing

The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. Chronic conditions such as diabetes mellitus or peripheral vascular diseases can lead to impaired wound healing. Skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. This is a complex process, which is dependent on many cell types and mediators interacting in a highly sophisticated temporal sequence. Although some interactions during the healing process are crucial, redundancy is high and other cells or mediators can adopt functions or signaling without major complications. Mesenchymal stem cells have an alternative role due to special properties such as the capacity for self-renewal and multi-lineage differentiation, immunomodulatory effect, alleviation of inflammatory response, induction of angiogenesis, regulation of extracellular matrix remodeling, excellent migration and secretion of growth factors and cytokines in wound healing. We summarized current research on the mechanisms of mesenchymal stem cells with their isolation, specific markers, differentiation capacity, and the functional activities to evaluate wound healing application.

Silymarin improved diet-induced liver damage and insulin resistance by decreasing inflammation in mice

Context: Silymarin is the main flavonoid extracted from milk thistle, which has been used to treat liver diseases.Objective: The in vivo effect of silymarin on HFD-induced insulin resistance and fatty liver in mice was studied.Materials and methods: Male C57BL/6 mice were fed with high-fat diet (HFD) to induce obesity and insulin resistance and treated with 30, 60 mg/kg silymarin for 18 days. Food intake, body weight and the content/histology of epididymal fat and liver tissue were examined; the content of lipids, AST, ALT and inflammatory cytokines in serum were estimated.Results: Administration of silymarin caused bodyweight loss in diet induced obesity (DIO) mice (HFD group: 47.7 g, 60 mg/kg group: 43.0 g) while the food intake remain unchanged. Silymarin (60 mg/kg) significantly reduced the epididymal fat mass (from 1.75 g to 1.12 g). Elevated plasma lipids (TC 6.1 mM, TG 1.3 mM, LDL 1.2 mM) in DIO mice were all suppressed by silymarin (TC 4.5 mM, TG 0.89 mM, LDL 0.9 mM), as well as insulin (5.1 ng/ml in HFD group to 2.0 ng/ml (60 mg/kg silymarin). Examination of cytokine levels (TNF-α, IL-1β and IL-6) in each group proved that silymarin treatment significantly decreased inflammation in DIO mice. Finally, silymarin effectively protected liver from HFD-induced injury as evidenced by decreasing histological damage and reducing ALT and AST levels, as follows: ALT; 47.4 U/L in HFD group to 28.4 U/L (60 mg/kg silymarin); AST; 150.1 U/L in HFD group to 88.1 U/L (60 mg/kg silymarin) in serum.Discussion and conclusion: Our results suggested that silymarin-induced alleviation of inflammatory response could be a mechanism responsible for its benefits against liver damage and insulin resistance.

Autotransplantation of circulating endothelial progenitor cells protects against lipopolysaccharide-induced acute lung injury in rabbit

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are leading causes of morbidity and mortality in critically ill patients. Recent studies suggest that endothelial progenitor cells (EPCs) transplantation could become a novel cell-based therapeutic strategy for ALI/ARDS, but the exact therapeutic effect and possible mechanisms still need to be elucidated. In the present study, autologous circulating EPCs were obtained from rabbits using Ficoll centrifugation and cultured in vitro for 7days. ALI was induced in rabbits by lipopolysaccharide (LPS), and EPCs were administered systemically. Fluorescence microscopy showed that CM-DiI labelled EPCs could migrate to the injured lung tissues. Reduced pulmonary edema level, inflammation, hemorrhage and hyaline membrane formation were present in rabbit treated with EPCs. EPCs autotransplantation significantly decreased the expression of adhesion molecules of sICAM-1 and P-selectin. Furthermore, EPCs administration mediated a down-regulation of proinflammatory responses (reducing IL-1β and TNF-α) while increasing the anti-inflammatory cytokine IL-10. Apoptosis of endothelial and epithelial cells was substantially reduced in EPCs-treated rabbit. Those findings suggest that autotransplantation of circulating EPCs can reduce the severity of LPS-induced ALI. Possible mechanisms include EPCs engraftment and reendothelization, down-regulation of adhesion molecules, alleviation of inflammatory response and apoptosis prevention.