Oxidative Stress Reducing Osteogenesis Reversed by Curcumin via NF-κB Signaling and Had a Role in Anti-Osteoporosis

2021 ◽  
Author(s):  
Xu JiaQiang ◽  
Ran Gao ◽  
Wen Liang ◽  
ChangJian Wu ◽  
FangLing Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Calcium Content ◽  
Dependent Manner ◽  
Osteoporosis Prevention ◽  
High Concentration ◽  
Mineral Density

Abstract Objective: Curcumin has good anti-inflammatory and antioxidant properties, and whether it can resist osteoporosis through oxidative stress pathway in a dose-dependent manner.Method: we used an oxidative stress cell model by culture cells with hydrogen peroxide (H2O2), cells were osteogenic differentiation after treated with H2O2，different concentration curcumin were added during differentiation, then measured the early and late osteogenic index, and detected the potential signaling pathway involved. In addition, we employed rat OVX model treated with curcumin to confirm the protection of the anti-oxidant.Result: Low concentrations of curcumin (1-10μM) promoted the proliferation of MC3T3-E1 cells, improved alkaline phosphatase (ALP) activity, elevated calcium content against oxidative stress induced by H2O2, but high concentration (20 μM) failed, moreover, curcumin diminished supernatant receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-6 expression, inhibited the intracellular ROS triggered by H2O2, Notably, curcumin exerted protection by blocking the NF-κB signaling pathway. The curcumin administered for 12 weeks partially reversed the raito of blood malondialdehyde (MDA) and glutathione (GSH) activity in ovariectomized (OVX) rat in vivo. It also increased the bone mineral density (BMD) and improved the micro-architecture of trabecular bones. Conclusion: curcumin exerted protection on osteoporosis, the effect linked to a reduction of oxidative stress and bone resorbing cytokine, This study suggests that curcumin might be a candidate for osteoporosis prevention and the low concentration exerted obviously protection.

scholarly journals Upregulation of SIRT1 by Kartogenin Enhances Antioxidant Functions and Promotes Osteogenesis in Human Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Yifan Wang ◽  
Guangdong Chen ◽  
Jinku Yan ◽  
Xi Chen ◽  
Fan He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Cartilage Repair ◽  
Antioxidant Properties ◽  
Joint Disease ◽  
Dependent Manner

Osteoarthritis is a chronic degenerative joint disease involving both articular cartilage and subchondral bone. Kartogenin (KGN) was recently identified to improve in vivo cartilage repair; however, its effect on bone formation is unknown. The aim of this study was to investigate the effect of KGN on antioxidant properties and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). Human BM-MSCs were treated with KGN at concentrations ranging from 10−8 M to 10−6 M. Our results indicated that KGN improved cell proliferation and attenuated intracellular reactive oxygen species. The levels of antioxidant enzymes and osteogenic differentiation of BM-MSCs were enhanced by KGN in a dose-dependent manner. Furthermore, KGN-treated BM-MSCs showed upregulation of silent information regulator type 1 (SIRT1) and increased phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK), indicating that KGN activated the AMPK-SIRT1 signaling pathway in BM-MSCs. Inhibition of SIRT1 by nicotinamide reversed the antioxidant effect of KGN on BM-MSCs and suppressed osteogenic differentiation. In conclusion, our results demonstrated that KGN improved intracellular antioxidant properties and promoted osteogenic differentiation of BM-MSCs by activating the AMPK-SIRT1 signaling pathway. Thus, KGN may have the potential for not only articular cartilage repair but also the clinical application of MSCs in bone tissue engineering.

scholarly journals A Study on the Quality and Identity of Brazilian Pampa Biome Honey: Evidences for Its Beneficial Effects against Oxidative Stress and Hyperglycemia

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
L. C. Cruz ◽  
J. E. S. Batista ◽  
A. P. P. Zemolin ◽  
M. E. M. Nunes ◽  
D. B. Lippert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Antioxidant Properties ◽  
High Concentration ◽  
Beneficial Effects ◽  
Pampa Biome ◽  
First Time

We characterized, for the first time, the quality and identity of Brazilian Pampa biome honey and its antioxidant propertiesin vitro(FRAP, DDPH and ABTS). The potential protective effect of honey against oxidative stress induced by iron (Fe) and paraquat, (PQ) in aDrosophila melanogastermodel (in vivo) was also tested. The results indicated that all honey samples tested showed antioxidant activityin vitro. Flies treated with honey showed increased lifespan and were protected against oxidative stress induced by Fe and PQ. Despite the high concentration of sugars in honey (approximately 70–80%), our results demonstrate a hypoglycemic-like effect of honey inDrosophila. Thus, this study demonstrates the high quality of Brazilian Pampa biome honey as well as its significant antioxidant activityin vitroandin vivo, pointing to the potential use of this natural product as an alternative in the therapy of oxidative stress-associated diseases.

Hexagonal boron nitride nanoparticles trigger oxidative stress by modulating thiol/disulfide homeostasis

2021 ◽  
pp. 096032712110028
Author(s):  
F Kar ◽  
İ Söğüt ◽  
C Hacıoğlu ◽  
Y Göncü ◽  
H Şenturk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Boron Nitride ◽  
Hexagonal Boron Nitride ◽  
Chemical Properties ◽  
Heart Tissue ◽  
Albino Rats ◽  
Dependent Manner ◽  
Tissue Samples ◽  
Boron Nitride Nanoparticles

Background: Hexagonal boron nitride nanoparticles (hBN NPs) are encouraging nanomaterials with unique chemical properties in medicine and biomedical fields. Until now, the optimal hBN NP’s dosage and biochemical mechanism that can be used for in vivo systems has not been fully revealed. The main aim of this article is to reveal characteristics, serum and tissue interactions and any acute cytotoxic effect of different dose of hBN NPs for the first time. Methods: hBN NPs at concentrations varying between 50–3200 µg/kg was administered by intravenous injection to Wistar albino rats (n = 80) divided into seven dosage and control groups. Blood and tissue samples were taken after 24 hours. Results: Our findings suggested that higher doses hBN NPs caused oxidative stress on the serum of rats dose-dependently. However, hBN NPs did not affect thiol/disulfide homeostasis on kidney, liver, spleen, pancreas and heart tissue of rats. Furthermore, hBN NPs increased serum disulfide formation by disrupting the thiol/disulfide balance in rats. Also, LOOH and MPO levels increased at high doses, while CAT levels decreased statistically. Conclusion: The results revealed that hBN NPs induce oxidative stress in a dose-dependent manner by modulating thiol/disulfide homeostasis in rats at higher concentrations

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

Hyperglycemia Promotes Pancreatic Cancer Initiation and Progression by Activating the Wnt/β-Catenin Signaling Pathway

2021 ◽  
Vol 21 ◽  
Author(s):  
Huiming Chen ◽  
Junfeng Zhao ◽  
Ningning Jiang ◽  
Zheng Wang ◽  
Chang Liu
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Precancerous Lesions ◽  
Clinical Specimen ◽  
Ductal Adenocarcinoma ◽  
Dependent Manner ◽  
Pancreatic Cancer Cells ◽  
Cancer Initiation

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, with a 5-year survival rate of less than 10% because of the limited knowledge of tumor-promoting factors and their underlying mechanism. Diabetes mellitus (DM) and hyperglycemia are risk factors for many cancers, including PDAC, that modulate multiple downstream signaling pathways, such as the wingless/integrated (Wnt)/β-catenin signaling pathway. However, whether hyperglycemia promotes PDAC initiation and progression by activating the Wnt/β-catenin signaling pathway remains unclear. Methods: In this study, we used bioinformatics analysis and clinical specimen analysis to evaluate the activation states of the Wnt/βcatenin signaling pathway. In addition, colony formation assays, Transwell assays and wound-healing assays were used to evaluate the malignant biological behaviors of pancreatic cancer cells (PCs) under hyperglycemic conditions. To describe the effects of hyperglycemia and the Wnt/β-catenin signaling pathway on the initiation of PDAC, we used pancreatitis-driven pancreatic cancer initiation models in vivo and pancreatic acinar cell 3-dimensional culture in vitro. Results: Wnt/β-catenin signaling pathway-related molecules were overexpressed in PDAC tissues/cells and correlated with poor prognosis in PDAC patients. In addition, hyperglycemia exacerbated the abnormal activation of β-catenin in PDAC and enhanced the malignant biological behaviors of PCs in a Wnt/β-catenin signaling pathway-dependent manner. Indeed, hyperglycemia accelerated the formation of pancreatic precancerous lesions by activating the Wnt/β-catenin signaling pathway in vivo and in vitro. Conclusion: Hyperglycemia promotes pancreatic cancer initiation and progression by activating the Wnt/β-catenin signaling pathway.

scholarly journals Mn Inhibits GSH Synthesis via Downregulation of Neuronal EAAC1 and Astrocytic xCT to Cause Oxidative Damage in the Striatum of Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Xinxin Yang ◽  
Haibo Yang ◽  
Fengdi Wu ◽  
Zhipeng Qi ◽  
Jiashuo Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Dependent Manner ◽  
Protein Levels ◽  
Key Factor ◽  
Protein Sulfhydryl ◽  
Mrna And Protein Expression ◽  
The Brain

Excessive manganese (Mn) can accumulate in the striatum of the brain following overexposure. Oxidative stress is a well-recognized mechanism in Mn-induced neurotoxicity. It has been proven that glutathione (GSH) depletion is a key factor in oxidative damage during Mn exposure. However, no study has focused on the dysfunction of GSH synthesis-induced oxidative stress in the brain during Mn exposure. The objective of the present study was to explore the mechanism of Mn disruption of GSH synthesis via EAAC1 and xCT in vitro and in vivo. Primary neurons and astrocytes were cultured and treated with different doses of Mn to observe the state of cells and levels of GSH and reactive oxygen species (ROS) and measure mRNA and protein expression of EAAC1 and xCT. Mice were randomly divided into seven groups, which received saline, 12.5, 25, and 50 mg/kg MnCl2, 500 mg/kg AAH (EAAC1 inhibitor) + 50 mg/kg MnCl2, 75 mg/kg SSZ (xCT inhibitor) + 50 mg/kg MnCl2, and 100 mg/kg NAC (GSH rescuer) + 50 mg/kg MnCl2 once daily for two weeks. Then, levels of EAAC1, xCT, ROS, GSH, malondialdehyde (MDA), protein sulfhydryl, carbonyl, 8-hydroxy-2-deoxyguanosine (8-OHdG), and morphological and ultrastructural features in the striatum of mice were measured. Mn reduced protein levels, mRNA expression, and immunofluorescence intensity of EAAC1 and xCT. Mn also decreased the level of GSH, sulfhydryl, and increased ROS, MDA, 8-OHdG, and carbonyl in a dose-dependent manner. Injury-related pathological and ultrastructure changes in the striatum of mice were significantly present. In conclusion, excessive exposure to Mn disrupts GSH synthesis through inhibition of EAAC1 and xCT to trigger oxidative damage in the striatum.

scholarly journals Effects of Nrf2 Deficiency on Bone Microarchitecture in an Experimental Model of Osteoporosis

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Lidia Ibáñez ◽  
María Luisa Ferrándiz ◽  
Rita Brines ◽  
David Guede ◽  
Antonio Cuadrado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Bone Metabolism ◽  
Bone Microarchitecture ◽  
Related Factor ◽  
Mineral Density ◽  
Trabecular Bone Mineral Density ◽  
Bone Marrow Derived Cells

Objective. Redox imbalance contributes to bone fragility. We have evaluated the in vivo role of nuclear factor erythroid derived 2-related factor-2 (Nrf2), an important regulator of cellular responses to oxidative stress, in bone metabolism using a model of postmenopausal osteoporosis.Methods. Ovariectomy was performed in both wild-type and mice deficient in Nrf2 (Nrf2−/−). Bone microarchitecture was analyzed byμCT. Serum markers of bone metabolism were also measured. Reactive oxygen species production was determined using dihydrorhodamine 123.Results. Sham-operated or ovariectomized Nrf2−/−mice exhibit a loss in trabecular bone mineral density in femur, accompanied by a reduction in cortical area in vertebrae. Nrf2 deficiency tended to increase osteoblastic markers and significantly enhanced osteoclastic markers in sham-operated animals indicating an increased bone turnover with a main effect on bone resorption. We have also shown an increased production of oxidative stress in bone marrow-derived cells from sham-operated or ovariectomized Nrf2−/−mice and a higher responsiveness of bone marrow-derived cells to osteoclastogenic stimuli in vitro.Conclusion. We have demonstrated in vivo a key role of Nrf2 in the maintenance of bone microarchitecture.

scholarly journals Methylprednisolone Protects SAP and Pancreatitis-Associated ALI in Mice by Inhibiting NLRP3 Inflammasome Through NF-κB

2020 ◽  
Author(s):  
Chuan-jiang Liu ◽  
Qiang Fu ◽  
Wenjing Zhou ◽  
Xu Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Nlrp3 Inflammasome ◽  
Antioxidant Properties ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Dependent Manner ◽  
Expression Levels ◽  
Tnf Α

Abstract Background: Methylprednisolone (MP) is a synthetic corticosteroid with potent anti-inflammatory and antioxidant properties used as therapy for a variety of diseases. The underlying mechanism of MP to reduce acute pancreatitis still needs to be elucidated.Methods: Twenty-four male C57BL/6 mice (6-8 weeks) were used to establish SAP mouse model by administering an intraperitoneal injection of Cae and LPS. Amylase expression levels of serum and PLF were measured with an amylase assay kit. The concentrations of IL-1β and TNF-α in the serum and PLF were detected by ELISA. The level of pancreatic and lung tissue damage and inflammation was assessed by H&E staining and immunofluorescence staining. Western blot and qPCR were used to detect the expression levels of NLRP3, IL-1β and TNF-αin vivo and in vitro.Results: In this study, we found MP, used in the early phase of SAP, decreased the levels of IL-1β and TNF-α in serum and peritoneal lavage fluids (PLF), reduced the level of serum amylase and the expression of MPO in lung tissue, attenuated the pathological injury of the pancreas and lungs in a dose-dependent manner. The expression of NLRP3 and IL-1β in pancreas and lungs was down-regulated significantly depending on the MP concentration. In vitro, MP reduced the levels of IL-1β and TNF-α by down-regulating the expression of NLRP3, IL-1β and p-NF-κB in isolated peritoneal macrophages. Conclusion: MP can attenuate the injury of pancreas and lungs, and the inflammatory response in SAP mice by down-regulating the activation of NF-κB and the NLRP3 inflammasome.

scholarly journals Isolation, Characterization and Neuroprotective Activity of Folecitin: An In Vivo Study

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 825
Author(s):  
Umar Farooq ◽  
Taous Khan ◽  
Shahid Ali Shah ◽  
Md. Sanower Hossain ◽  
Yousaf Ali ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Nlrp3 Inflammasome ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Neuroprotective Activity ◽  
Bioactive Metabolites ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Rat Pups

Neurodegenerative diseases (NDs) extend the global health burden. Consumption of alcohol as well as maternal exposure to ethanol can damage several neuronal functions and cause cognition and behavioral abnormalities. Ethanol induces oxidative stress that is linked to the development of NDs. Treatment options for NDs are yet scarce, and natural product-based treatments could facilitate ND management since plants possess plenty of bioactive metabolites, including flavonoids, which typically demonstrate antioxidant and anti-inflammatory properties. Hypericum oblongifolium is an important traditional medicinal plant used for hepatitis, gastric ulcer, external wounds, and other gastrointestinal disorders. However, it also possesses multiple bioactive compounds and antioxidant properties, but the evaluation of isolated pure compounds for neuroprotective efficacy has not been done yet. Therefore, in the current study, we aim to isolate and characterize the bioactive flavonoid folecitin and evaluate its neuroprotective activity against ethanol-induced oxidative-stress-mediated neurodegeneration in the hippocampus of postnatal day 7 (PND-7) rat pups. A single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7. This caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-1) proteins to form a complex called the NLRP3-inflammasome, which converts pro-interleukin 1 beta (IL-1B) to activate IL-1B and induce widespread neuroinflammation and neurodegeneration. In contrast, co-administration of folecitin (30 mg/kg body weight) reduced ethanol-induced oxidative stress, inhibited p-JNK, and deactivated the NLRP3-inflammasome complex. Furthermore, folecitin administration reduced neuroinflammatory and neurodegenerative protein markers, including decreased caspase-3, BCL-2-associated X protein (BAX), B cell CLL/lymphoma 2 (BCL-2), and poly (ADP-ribose) polymerase-1 (PARP-1) expression in the immature rat brain. These findings conclude that folecitin is a flavone compound, and it might be a novel, natural and safe agent to curb oxidative stress and its downstream harmful effects, including inflammasome activation, neuroinflammation, and neurodegeneration. Further evaluation in a dose-dependent manner would be worth it in order to find a suitable dose regimen for NDs.

scholarly journals Protection of the vascular endothelium in experimental situations

2011 ◽  
Vol 4 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Ružena Sotníková ◽  
Jana Nedelčevová ◽  
Jana Navarová ◽  
Viera Nosáľová ◽  
Katarína Drábiková ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vascular Endothelium ◽  
Vascular Dysfunction ◽  
Antioxidant Properties ◽  
Pharmacological Intervention ◽  
Ros Production ◽  
Nitric Oxide Radical ◽  
Endothelium Dependent Relaxation

Protection of the vascular endothelium in experimental situationsOne of the factors proposed as mediators of vascular dysfunction observed in diabetes is the increased generation of reactive oxygen species (ROS). This provides support for the use of antioxidants as early and appropriate pharmacological intervention in the development of late diabetic complications. In streptozotocin (STZ)-induced diabetes in rats we observed endothelial dysfuction manifested by reduced endothelium-dependent response to acetylcholine of the superior mesenteric artery (SMA) and aorta, as well as by increased endothelaemia. Changes in endothelium-dependent relaxation of SMA were induced by injury of the nitric oxide radical (·NO)-signalling pathway since the endothelium-derived hyperpolarising factor (EDHF)-component of relaxation was not impaired by diabetes. The endothelial dysfunction was accompanied by decreased ·NO bioavailabity as a consequence of reduced activity of eNOS rather than its reduced expression. The results obtained using the chemiluminiscence method (CL) argue for increased oxidative stress and increased ROS production. The enzyme NAD(P)H-oxidase problably participates in ROS production in the later phases of diabetes. Oxidative stress was also connected with decreased levels of reduced glutathione (GSH) in the early phase of diabetes. After 10 weeks of diabetes, adaptational mechanisms probably took place because GSH levels were not changed compared to controls. Antioxidant properties of SMe1EC2 foundin vitrowere partly confirmedin vivo.Administration of SMe1EC2 protected endothelial function. It significantly decreased endothelaemia of diabetic rats and improved endothelium-dependent relaxation of arteries, slightly decreased ROS-production and increased bioavailability of ·NO in the aorta. Further studies with higher doses of SMe1EC2 may clarify the mechanism of its endothelium-protective effectin vivo.

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