scholarly journals The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2163 ◽  
Author(s):  
Nilson Carlos Ferreira Junior ◽  
Maurício dos Santos Pereira ◽  
Nour Francis ◽  
Paola Ramirez ◽  
Paula Martorell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Inflammatory Responses ◽  
Parent Compound ◽  
Antioxidant Properties ◽  
Microglial Cells ◽  
Activated Microglia ◽  
Tnf Α ◽  
Immunosuppressive Action ◽  
Anti Inflammatory

We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.

scholarly journals In Vitro Evaluation of the Anti-Inflammatory Effect of KMUP-1 and in Vivo Analysis of Its Therapeutic Potential in Osteoarthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 615
Author(s):  
Shang-En Huang ◽  
Erna Sulistyowati ◽  
Yu-Ying Chao ◽  
Bin-Nan Wu ◽  
Zen-Kong Dai ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Serum Levels ◽  
Gene Expressions ◽  
Tnf Α ◽  
Anti Inflammatory

Osteoarthritis is a degenerative arthropathy that is mainly characterized by dysregulation of inflammatory responses. KMUP-1, a derived chemical synthetic of xanthine, has been shown to have anti-inflammatory and antioxidant properties. Here, we aimed to investigate the in vitro anti-inflammatory and in vivo anti-osteoarthritis effects of KMUP-1. Protein and gene expressions of inflammation markers were determined by ELISA, Western blotting and microarray, respectively. RAW264.7 mouse macrophages were cultured and pretreated with KMUP-1 (1, 5, 10 μM). The productions of TNF-α, IL-6, MMP-2 and MMP- 9 were reduced by KMUP-1 pretreatment in LPS-induced inflammation of RAW264.7 cells. The expressions of iNOS, TNF-α, COX-2, MMP-2 and MMP-9 were also inhibited by KMUP-1 pretreatment. The gene expression levels of TNF and COX families were also downregulated. In addition, KMUP-1 suppressed the activations of ERK, JNK and p38 as well as phosphorylation of IκBα/NF-κB signaling pathways. Furthermore, SIRT1 inhibitor attenuated the inhibitory effect of KMUP-1 in LPS-induced NF-κB activation. In vivo study showed that KMUP-1 reduced mechanical hyperalgesia in monoiodoacetic acid (MIA)-induced rats OA. Additionally, KMUP-1 pretreatment reduced the serum levels of TNF-α and IL-6 in MIA-injected rats. Moreover, macroscopic and histological observation showed that KMUP-1 reduced articular cartilage erosion in rats. Our results demonstrated that KMUP-1 inhibited the inflammatory responses and restored SIRT1 in vitro, alleviated joint-related pain and cartilage destruction in vivo. Taken together, KMUP-1 has the potential to improve MIA-induced articular cartilage degradation by inhibiting the levels and expression of inflammatory mediators suggesting that KMUP-1 might be a potential therapeutic agent for OA.

scholarly journals Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses

2021 ◽  
Author(s):  
Mamdooh Ghoneum ◽  
Mohamed S. A. El-Gerbed
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Biological Effects ◽  
Cellular Damage ◽  
Male Rats ◽  
Antioxidant Enzyme Activities ◽  
Oxidative Stress Biomarkers ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Liver Tissues

Abstract Purpose Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. Methods Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed. Results MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture. Conclusion HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.

scholarly journals Interdependence of Anti-Inflammatory and Antioxidant Properties of Squalene–Implication for Cardiovascular Health

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 103
Author(s):  
Nurul ‘Izzah Ibrahim ◽  
Isa Naina Mohamed
Keyword(s):  
Oxidative Stress ◽  
Risk Factors ◽  
Cardiovascular Health ◽  
Inflammatory Responses ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Unsaturated Hydrocarbon ◽  
Alternative Medicines ◽  
Lower Density Lipoprotein ◽  
Anti Inflammatory

Cardiovascular diseases (CVD) have been recognized as the leading cause of mortality worldwide, accounting for 31% of global mortality. Among the risk factors of CVD, hyperlipidemia has been established as the most potent risk factor. Statins, a class of drug that reduces lower-density lipoprotein cholesterol (LDL-C), are the preferred medical treatment. However, due to the development of statin-associated muscle symptoms, statins are associated with patients’ discontinuation and nonadherence. Other statin-induced side effects, such as hepatotoxicity and gastrointestinal upset, all contribute to patients choosing alternative medicines. Squalene (SQ), an unsaturated hydrocarbon naturally synthesized in plants and animals, could become the alternative treatment or supplementary agent for cardiovascular health. SQ has been shown to exert cardioprotective effect via its antioxidant activity. Oxidative stress and inflammatory responses are closely related to each other, which proposes an interdependence relation between antioxidant and anti-inflammatory. Therefore, this review explores the interdependence between the antioxidant and anti-inflammatory effects of SQ implicated on cardiovascular health.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Beta Amyloid ◽  
Microglial Cells ◽  
Root Extracts ◽  
Tnf Α ◽  
P38α Mapk ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

scholarly journals Anti-Inflammatory Effect and Cellular Uptake Mechanism of Carbon Nanodots in in Human Microvascular Endothelial Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1247
Author(s):  
Sarah Belperain ◽  
Zi Yae Kang ◽  
Andrew Dunphy ◽  
Brandon Priebe ◽  
Norman H. L. Chiu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Synthesis Method ◽  
Microvascular Endothelial Cells ◽  
Carbon Nanodots ◽  
Uptake Mechanism ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Microvascular Endothelial

Cardiovascular disease (CVD) has become an increasingly important topic in the field of medical research due to the steadily increasing rates of mortality caused by this disease. With recent advancements in nanotechnology, a push for new, novel treatments for CVD utilizing these new materials has begun. Carbon Nanodots (CNDs), are a new form of nanoparticles that have been coveted due to the green synthesis method, biocompatibility, fluorescent capabilities and potential anti-antioxidant properties. With much research pouring into CNDs being used as bioimaging and drug delivery tools, few studies have been completed on their anti-inflammatory potential, especially in the cardiovascular system. CVD begins initially by endothelial cell inflammation. The cause of this inflammation can come from many sources; one being tumor necrosis factor (TNF-α), which can not only trigger inflammation but prolong its existence by causing a storm of pro-inflammatory cytokines. This study investigated the ability of CNDs to attenuate TNF-α induced inflammation in human microvascular endothelial cells (HMEC-1). Results show that CNDs at non-cytotoxic concentrations reduce the expression of pro-inflammatory genes, mainly Interleukin-8 (IL-8), and interleukin 1 beta (IL-1β). The uptake of CNDs by HMEC-1s was examined. Results from the studies involving channel blockers and endocytosis disruptors suggest that uptake takes place by endocytosis. These findings provide insights on the interaction CNDs and endothelial cells undergoing TNF-α induced cellular inflammation.

scholarly journals Alpha-Lipoic Acid Protects Cardiomyocytes against Heat Stroke-Induced Apoptosis and Inflammatory Responses Associated with the Induction of Hsp70 and Activation of Autophagy

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hsin-Hsueh Shen ◽  
Yu-Shiuan Tseng ◽  
Ni-Chun Kuo ◽  
Ching-Wen Kung ◽  
Sherif Amin ◽  
...  
Keyword(s):  
Lipoic Acid ◽  
Myocardial Injury ◽  
Inflammatory Responses ◽  
Heat Stroke ◽  
Heat Exposure ◽  
Antioxidant Properties ◽  
Mitochondrial Enzymes ◽  
Protective Effects ◽  
Anion Formation ◽  
Anti Inflammatory

Heat stroke (HS) is a life-threatening illness and defined as when body temperature elevates above 40°C accompanied by the systemic inflammatory response syndrome that results in multiple organ dysfunctions. α-Lipoic acid (ALA) acts as a cofactor of mitochondrial enzymes and exerts anti-inflammatory and antioxidant properties in a variety of diseases. This study investigates the beneficial effects of ALA on myocardial injury and organ damage caused by experimental HS and further explores its underlying mechanism. Male Wistar rats were exposed to 42°C until their rectal core temperature reached 42.9°C and ALA was pretreared 40 or 80 mg/kg (i.v.) 1.5 h prior to heat exposure. Results showed that HS-induced lethality and hypothermia were significantly alleviated by ALA treatment that also improved plasma levels of CRE, LDH, and CPK and myocardial injury biomarkers myoglobin and troponin. In addition, ALA reduced cardiac superoxide anion formation and protein expression of cleaved caspase 3 caused by HS. Proinflammatory cytokine TNF-α and NF-κB pathways were significantly reduced by ALA treatment which may be associated with the upregulation of Hsp70. ALA significantly increased the Atg5-12 complex and LC3B II/LC3B I ratio, whereas the p62 and p-mTOR expression was attenuated in HS rats, indicating the activation of autophagy by ALA. In conclusion, ALA ameliorated the deleterious effects of HS by exerting antioxidative and anti-inflammatory capacities. Induction of Hsp70 and activation of autophagy contribute to the protective effects of ALA in HS-induced myocardial injury.

scholarly journals Effect of Dietary Conjugated Linoleic Acid Supplementation on Early Inflammatory Responses during Cutaneous Wound Healing

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Na-Young Park ◽  
Giuseppe Valacchi ◽  
Yunsook Lim
Keyword(s):  
Oxidative Stress ◽  
Wound Healing ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Wound Closure ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Cutaneous Wound Healing ◽  
Cutaneous Wound ◽  
Anti Inflammatory

Inflammatory response is considered the most important period that regulates the entire healing process. Conjugated linoleic acid (CLA), a class of linoleic acid positional and geometric isomers, is well known for its antioxidant and anti-inflammatory properties. We hypothesized that dietary CLA supplementation accelerates cutaneous wound healing by regulating antioxidant and anti-inflammatory functions. To investigate wound closure rates and inflammatory responses, we used a full-thickness excisional wound model after 2-week treatments with control, 0.5%, or 1% CLA-supplemented diet. Mice fed dietary CLA supplementation had reduced levels of oxidative stress and inflammatory markers. Moreover, the wound closure rate was improved significantly in mice fed a 1% CLA-supplemented diet during early stage of wound healing (inflammatory stage). We conclude that dietary CLA supplementation enhances the early stage of cutaneous wound healing as a result of modulating oxidative stress and inflammatory responses.

scholarly journals IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

2016 ◽  
Vol 38 (6) ◽  
pp. 2163-2172 ◽  
Author(s):  
Xiaorong Hu ◽  
Ruisong Ma ◽  
Jiajia Lu ◽  
Kai Zhang ◽  
Weipan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Tunel Staining ◽  
Ischemia And Reperfusion ◽  
Stress Reactions ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Myocardial Ischemia And Reperfusion ◽  
Tnf Α ◽  
And Oxidative Stress

Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R) injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO) group, ischemia and reperfusion (I/R) group, (IL-23 + I/R) group and (anti-IL-23 + I/R) group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH), creatine kinase (CK) and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P < 0.05). Meanwhile, IL-23 significantly increased the expression of eIL-17A, TNF-α and IL-6 and enhanced both the increase of the MDA level and the decrease of the SOD level induced by I/R (all P<0.05). IL-23 had no effect on the expression of HMGB1 (p > 0.05). All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

Abstract 553: Siglec-1 (CD169) on Monocytes/Macrophages: A New Receptor For Extracellular Self-RNA in Triggering Inflammatory Responses via the Sheddase TACE/ADAM17

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
Extracellular Rna ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: &#8211;]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.

scholarly journals Curcumin and Endometriosis

2020 ◽  
Vol 21 (7) ◽  
pp. 2440 ◽  
Author(s):  
Alexandre Vallée ◽  
Yves Lecarpentier
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Uterine Cavity ◽  
Main Role ◽  
Oxygen Species ◽  
Inflammatory Agent ◽  
Gynecological Disorders ◽  
Anti Oxidant ◽  
Anti Inflammatory

Endometriosis is one of the main common gynecological disorders, which is characterized by the presence of glands and stroma outside the uterine cavity. Some findings have highlighted the main role of inflammation in endometriosis by acting on proliferation, apoptosis and angiogenesis. Oxidative stress, an imbalance between reactive oxygen species and antioxidants, could have a key role in the initiation and progression of endometriosis by resulting in inflammatory responses in the peritoneal cavity. Nevertheless, the mechanisms underlying this disease are still unclear and therapies are not currently efficient. Curcumin is a major anti-inflammatory agent. Several findings have highlighted the anti-oxidant, anti-inflammatory and anti-angiogenic properties of curcumin. The purpose of this review is to summarize the potential action of curcumin in endometriosis by acting on inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis.

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