scholarly journals Effects of Anchomanes difformis on Inflammation, Apoptosis, and Organ Toxicity in STZ-Induced Diabetic Cardiomyopathy

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 29
Author(s):  
Toyin D. Alabi ◽  
Novel N. Chegou ◽  
Nicole L. Brooks ◽  
Oluwafemi O. Oguntibeju
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Diabetic Complications ◽  
Type Ii Diabetes ◽  
Type Ii ◽  
Necrosis Factor Alpha ◽  
Fatty Acid Binding ◽  
Antioxidant Power ◽  
Anti Inflammatory

Persistent hyperglycemia is known to cause enhanced generation of reactive oxygen species in diabetes. Several inflammatory cytokines are induced by oxidative stress, and their release also leads to increased oxidative stress; this makes oxidative stress one of the important factors in the development of chronic inflammation and other immune responses. These have been implicated in the development of diabetic complications such as nephropathy and cardiomyopathy. Anchomanes difformis has been shown to possess antioxidant and anti-inflammatory potentials. The present study investigated the immunomodulatory potential and the antiapoptotic ability of Anchomanes difformis to ameliorate heart toxicity and injury in type II diabetes. Two weeks of fructose (10%) administration followed by single intraperitoneal injection of streptozotocin (40 mg/kg) were used to induce type II diabetes in male Wistar rats. Leaf extract (aqueous) of Anchomanes difformis (200 and 400 mg/kg) was administered orally for six weeks. Blood glucose concentrations and body weights before and after interventions were determined. Interleukin (IL)-1β, IL-6, IL-10, IL-18, monocyte chemoattractant protein 1 (MCP-1), and tumor necrosis factor alpha (TNFα) were measured in the heart homogenates. Catalase (CAT), superoxide dismutase (SOD), total protein, oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), thiobarbituric acid reactive substances (TBARS), and heart-type fatty acid-binding protein (H-FABP) levels were determined. Expressions of transcription factors (Nrf 2 and NFkB/p65) and apoptotic markers were also investigated in the heart. Anchomanes difformis administration reduced pro-inflammatory cytokines, increased anti-inflammatory markers, and enhanced antioxidant defense in the heart of diabetic treated animals. Anchomanes difformis is a new, promising therapeutic agent that can be explored for the treatment of pathological conditions associated with immune responses and will be a useful tool in the management of associated diabetic complications.

Abstract 243: Roles of TNF alpha and MCP-1 in Type II Diabetes-induced Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jiyeon Yang ◽  
Abbott C Louise ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Type Ii Diabetes ◽  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Heart Tissue ◽  
Type Ii ◽  
Necrosis Factor Alpha ◽  
Double Labeling ◽  
Monocyte Chemoattractant Protein 1

Tumor necrosis factor alpha (TNF) is reported to underlie a component of vascular inflammation and ensuing endothelial dysfunction in diabetes, but the role of inflammatory cells in these events is unknown. Because TNF reportedly induces monocyte chemoattractant protein-1 (MCP-1) expression, we hypothesized that the interaction between TNF and MCP-1 contributes to the evolution of vascular inflammation in diabetes. To test this hypothesis, expression of TNF and MCP-1, and formation of nitrotyrosine (N-Tyr, an indicator of peroxynitrite production) were determined in isolated coronary arterioles (50–100um) from genetically modified mice with Type II diabetes (Lepr db ) and the lean control heterozygotes (m Lepr db ). Protein and mRNA expression of TNF, protein expression of MCP-1, and presence of N-Tyr were significantly increased in arterioles from Lepr db mice compared to those from m Lepr db . Immunofluorescence double labeling revealed the prominent localization of MCP-1 to endothelium (Von Willebrand factor) of arterioles and venules. MCP-1 also co-localized with macrophages (CD68) in the heart tissue. To determine if MCP-1 may be key to the vascular inflammation and ensuing endothelial dysfunction, we administered anti-MCP-1 (10 μg/day, 3 days, i.p., n=4; to block MCP-1 signaling) in the mice and then determined endothelial dilation in isolated, cannulated pressurized (60 cmH2O) arterioles. Anti-MCP-1 restored dilation to acetylcholine in Lepr db mice by 35±2% (P<0.05 vs Lepr db mice without treatment, 9.8±4%) but did not affect dilation in m Lepr db mice. To establish interactions between TNF and MCP-1, we administered anti-TNF (72hr treatment; 0.625mg/kg, i.p.) to block TNF signaling and determined effects on MCP-1 and oxidative stress. After anti-TNF administration, expression of MCP-1 was decreased and numbers of MCP-1 positive cells were markedly reduced in Lepr db mice. Moreover, anti-TNF prevented the formation of N-Tyr in Lepr db mice. These findings demonstrate that the endothelial dysfunction occurring in type II diabetes is the result of the effects of the inflammatory cytokine TNF and TNF related signaling, including the expression of MCP-1, which also furthers the oxidative stress.

scholarly journals Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Maha Sellami ◽  
Shamma Al-muraikhy ◽  
Hend Al-Jaber ◽  
Hadaia Al-Amri ◽  
Layla Al-Mansoori ◽  
...  
Keyword(s):  
Immune Response ◽  
Telomere Length ◽  
Inflammatory Cytokines ◽  
Elite Athletes ◽  
Age Groups ◽  
Moderate Intensity ◽  
Necrosis Factor Alpha ◽  
Blood Samples ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

scholarly journals Antioxidant and anti-inflammatory effect of conjugated linolenic acid isomers against streptozotocin-induced diabetes

2011 ◽  
Vol 108 (6) ◽  
pp. 974-983 ◽  
Author(s):  
Siddhartha S. Saha ◽  
Mahua Ghosh
Keyword(s):  
Oxidative Stress ◽  
Linolenic Acid ◽  
Eleostearic Acid ◽  
Albino Rats ◽  
Punicic Acid ◽  
Conjugated Linolenic Acid ◽  
Frap Assay ◽  
Erythrocyte Morphology ◽  
Antioxidant Power ◽  
Anti Inflammatory

The present study was undertaken to evaluate the effect of α-eleostearic acid and punicic acid, two isomers of conjugated linolenic acid (CLnA) present in bitter gourd (Momordica charantia) and snake gourd oil (Trichosanthes anguina), respectively, against oxidative stress, inflammatory challenge and aberration in erythrocyte morphology due to streptozotocin (STZ)-induced diabetes. Male albino rats were divided into four groups consisting of eight animals in each group. The first group served as control and diabetes was induced in rats in groups 2–4 by a single intraperitoneal injection of STZ. Moreover, rats in groups 3 and 4 were treated with 0·5 % of α-eleostearic acid and 0·5 % of punicic acid of the total lipid given, respectively, by oral administration once per d. After administration, CLnA isomers had significantly reduced oxidative stress, lipid peroxidation and restored antioxidant and pro-inflammatory enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, reduced glutathione, NO synthase level in pancreas, blood and erythrocyte lysate. The ferric reducing antioxidant power (FRAP) assay of plasma showed that CLnA treatment caused improvement in the FRAP value which was altered after STZ treatment due to an increased level of free radicals. Expression of inflammatory cytokines such as TNF-α and IL-6 in blood and expression of hepatic NF-κB (p65) increased significantly after STZ treatment due to increased inflammation which was restored with the administration of CLnA isomers. From the obtained results, it could be concluded that α-eleostearic acid and punicic acid showed potent antioxidant and anti-inflammatory activity with varying effectivity.

scholarly journals Host F-box protein 22 enhances the uptake of Brucella by macrophages and drives a sustained release of pro-inflammatory cytokines through degradation of the anti-inflammatory effector proteins of Brucella.

2021 ◽  
Author(s):  
Girish Radhakrishnan ◽  
Varadendra Mazumdar ◽  
Kiranmai Joshi ◽  
Binita Roy Nandi ◽  
Swapna Namani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Cytokines ◽  
Effector Proteins ◽  
Host Protein ◽  
Limited Information ◽  
Phagocytic Cells ◽  
Scf Complex ◽  
Enhanced Production ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Brucella species are intracellular bacterial pathogens, causing the world-wide zoonotic disease, brucellosis.  Brucella invade professional and non-professional phagocytic cells, followed by resisting intracellular killing and establishing a replication permissive niche. Brucella also modulate the innate and adaptive immune responses of the host for their chronic persistence. The complex intracellular cycle of Brucella majorly depends on multiple host factors but limited information is available on host and bacterial proteins that play essential role in the invasion, intracellular replication and modulation of host immune responses. By employing an siRNA screening, we identified a role for the host protein, FBXO22 in Brucella -macrophage interaction. FBXO22 is the key element in the SCF E3 ubiquitination complex where it determines the substrate specificity for ubiquitination and degradation of various host proteins.  Downregulation of FBXO22 by siRNA or CRISPR-Cas9 system, resulted diminished uptake of Brucella into macrophages, which was dependent on NF-κB-mediated regulation of phagocytic receptors. FBXO22 expression was upregulated in Brucella -infected macrophages that resulted induction of phagocytic receptors and enhanced production of pro-inflammatory cytokines through NF-κB. Furthermore, we found that FBXO22 recruits the effector proteins of Brucella , including the anti-inflammatory proteins, TcpB and OMP25 for degradation through the SCF complex. We did not observe any role for another F-box containing protein of SCF complex, β-TrCP in Brucella -macrophage interaction. Our findings unravel novel functions of FBXO22 in host-pathogen interaction and its contribution to pathogenesis of infectious diseases.

Abstract 890: Feed-forward Signaling of TNF alpha and NFkappa B Produces Endothelial Dysfunction in Coronary Arterioles In Type Ii Diabetic Mice.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jiyeon Yang ◽  
Xiangbin Xu ◽  
Glen A Laine ◽  
Cuihua Zhang
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Type Ii ◽  
Diabetic Mice ◽  
Necrosis Factor Alpha ◽  
Paramagnetic Resonance ◽  
Feed Forward ◽  
Coronary Arterioles

Nuclear factor-κB (NFκB) signaling reportedly increases tumor necrosis factor-alpha (TNF expression), and the oxidative stress induced by TNF may then lead to further increase NFκB expression, i.e., a feed-forward interaction. Accordingly, we hypothesized that this feed-forward interaction between TNF and NFκB may amplify one another toward the evolution of vascular disease in diabetes. To test this hypothesis, we assessed the role of NFκB in endothelial dysfunction in Lepr db mice by evaluation of endothelial function of isolated coronary resistance vessels of m Lepr db (heterozygote, normal) and Lepr db (homozygote, diabetic) mice. Coronary arterioles (40 –100 μm) were isolated and pressurized (60 cmH2O) without flow. Although dilation of vessels to the endothelium-independent vasodilator, sodium nitroprusside (SNP) was not different between Lepr db and m Lepr db mice (n = 6), dilation to the endothelium-dependent agonist, acetycholine (ACh) was reduced (n = 5, P < 0.05). Electron Paramagnetic Resonance (EPR) results show that superoxide production was reduced by NFκB antagonist (MG-132), or anti-TNF in Lepr db mice suggesting that NFκB and TNF were contributing to elevated oxidative stress. MG-132 (1 μM, n = 4) antagonized the inhibitory effect of Lepr db mice on ACh-induced dilation vs. Lepr db without treatment, but did not affect dilation in m Lepr db mice. To better understand the basis for enhanced contributions of TNF and NFκB in diabetes, we used Western analysis to assess expression of major proteins involved in TNF-mediated signaling. Previous studies have provided compelling evidence that IKK beta plays an essential role in NFκB activation in response to TNF, whereas IKK alpha appears to play a lesser role; therefore, we examined the expression levels of IKK alpha and IKK beta mRNA and protein in Lepr db null for TNF. The protein concentration and mRNA expression level of IKK alpha were increased in Lepr db mice null for TNF (db TNF- /db TNF- ) mice. One intriguing finding of this study is that the roles of IKK alpha and IKK beta appear reversed in the inflammatory response in diabetic Lepr db mice. Furthermore, our results indicate that NFκB and TNF signaling interact to amplify the oxidative stress and induce endothelial dysfunction in type II diabetes.

scholarly journals Astilbe Chinensis ethanol extract suppresses inflammation in macrophages via NF-κB pathway

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Tae-Young Gil ◽  
Bo-Ram Jin ◽  
Chul-Hee Hong ◽  
Jong Hyuk Park ◽  
Hyo-Jin An
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Inflammatory Mediators ◽  
Ethanol Extract ◽  
Nuclear Factor Κb ◽  
Peritoneal Macrophages ◽  
Necrosis Factor Alpha ◽  
Iκb Kinase ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Macrophages play a crucial role in inflammation. Astilbe chinensis is one of perennial herbs belonging to the genus Astilbe. Plants in the genus have been used for pain, headaches, arthralgia, and chronic bronchitis. However, the effect of A.chinensis on inflammation remains unclear. To study the anti-inflammatory action of A.chinensis ethanol extract (ACE), we investigated the effect of ACE on the production of pro-inflammatory mediators and cytokines in macrophages. Methods We evaluated the effectiveness of ACE in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and thioglycollate (TG)-elicited peritoneal macrophages from male C57BL/6 mice. We measured the levels of pro-inflammatory mediators and cytokines, and examined the anti-inflammatory actions of ACE on nuclear factor κB (NF-κB) pathway in the macrophages. Western blot analysis and immunofluorescence microscopy were used to determine protein level and translocation, respectively. Results ACE suppressed the output of nitric oxide (NO), prostaglandin E2 (PGE2), and pro-inflammatory cytokines in stimulated macrophages via inhibiting the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins. ACE suppressed mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α). We examined the efficacies of ACE on NF-κB activation by measuring the expressions including IκB kinase (IKK), inhibitor of κB (IκB), and nuclear p65 proteins. In addition, the inhibition of NF-κB p65’s translocation was determined with immunofluorescence assay. Conclusion Our findings manifested that ACE inhibited LPS or TG-induced inflammation by blocking the NF-κB signaling pathway in macrophages. It indicated that ACE is a potential therapeutic mean for inflammation and related diseases.

scholarly journals Experimental Pretreatment with Chlorogenic Acid Prevents Transient Ischemia-Induced Cognitive Decline and Neuronal Damage in the Hippocampus through Anti-Oxidative and Anti-Inflammatory Effects

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3578 ◽  
Author(s):  
Tae-Kyeong Lee ◽  
Il-Jun Kang ◽  
Bora Kim ◽  
Hye Jin Sim ◽  
Dae- Won Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Chlorogenic Acid ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Fluoro Jade B ◽  
Anti Inflammatory

Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.

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