Gintonin-Enriched Fraction Suppresses Heat Stress-Induced Inflammation through LPA Receptor

Heat stress can be caused by various environmental factors. When exposed to heat stress, oxidative stress and inflammatory reaction occur due to an increase of reactive oxygen species (ROS) in the body. In particular, inflammatory responses induced by heat stress are common in muscle cells, which are the most exposed to heat stress and directly affected. Gintonin-Enriched Fraction (GEF) is a non-saponin component of ginseng, a glycolipoprotein. It is known that it has excellent neuroprotective effects, therefore, we aimed to confirm the protective effect against heat stress by using GEF. C2C12 cells were exposed to high temperature stress for 1, 12 and 15 h, and the expression of signals was analyzed over time. Changes in the expression of the factors that were observed under heat stress were confirmed at the protein level. Exposure to heat stress increases phosphorylation of p38 and extracellular signal-regulated kinase (ERK) and increases expression of inflammatory factors such as NLRP3 inflammasome through lysophosphatidic acid (LPA) receptor. Activated inflammatory signals also increase the secretion of inflammatory cytokines such as interleukin 6 (IL-6) and interleukin 18 (IL-18). Also, expression of glutathione reductase (GR) and catalase related to oxidative stress is increased. However, it was confirmed that the changes due to the heat stress were suppressed by the GEF treatment. Therefore, we suggest that GEF helps to protect heat stress in muscle cell and prevent tissue damage by oxidative stress and inflammation.

Download Full-text

Lipopolysaccharide induces neuroglia activation and NF-κB activation in cerebral cortex of adult mice

Laboratory Animal Research ◽

10.1186/s42826-019-0018-9 ◽

2019 ◽

Vol 35 (1) ◽

Cited By ~ 4

Author(s):

Ju-Bin Kang ◽

Dong-Ju Park ◽

Murad-Ali Shah ◽

Myeong-Ok Kim ◽

Phil-Ok Koh

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Calcium Binding ◽

Inflammatory Responses ◽

Inflammatory Factors ◽

Adult Mice ◽

Tnf Α ◽

Factor Α ◽

And Oxidative Stress ◽

Necrosis Factor

Abstract Lipopolysaccharide (LPS) acts as an endotoxin, releases inflammatory cytokines, and promotes an inflammatory response in various tissues. This study investigated whether LPS modulates neuroglia activation and nuclear factor kappa B (NF-κB)-mediated inflammatory factors in the cerebral cortex. Adult male mice were divided into control animals and LPS-treated animals. The mice received LPS (250 μg/kg) or vehicle via an intraperitoneal injection for 5 days. We confirmed a reduction of body weight in LPS-treated animals and observed severe histopathological changes in the cerebral cortex. Moreover, we elucidated increases of reactive oxygen species and oxidative stress levels in LPS-treated animals. LPS administration led to increases of ionized calcium-binding adaptor molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Iba-1 and GFAP are well accepted as markers of activated microglia and astrocytes, respectively. Moreover, LPS exposure induced increases of NF-κB and pro-inflammatory factors, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Increases of these inflammatory mediators by LPS exposure indicate that LPS leads to inflammatory responses and tissue damage. These results demonstrated that LPS activates neuroglial cells and increases NF-κB-mediated inflammatory factors in the cerebral cortex. Thus, these findings suggest that LPS induces neurotoxicity by increasing oxidative stress and activating neuroglia and inflammatory factors in the cerebral cortex.

Download Full-text

Gypenosides Prevent H2O2-Induced Retinal Ganglion Cell Apoptosis by Concurrently Suppressing the Neuronal Oxidative Stress and Inflammatory Response

Journal of Molecular Neuroscience ◽

10.1007/s12031-019-01468-9 ◽

2020 ◽

Vol 70 (4) ◽

pp. 618-630 ◽

Cited By ~ 1

Author(s):

Hong-Kan Zhang ◽

Yuan Ye ◽

Kai-Jun Li ◽

Zhen-ni Zhao ◽

Jian-Feng He

Keyword(s):

Oxidative Stress ◽

Optic Neuritis ◽

Ganglion Cells ◽

Nerve Fibers ◽

Inflammatory Factors ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Retinal Ganglion ◽

Apoptotic Pathway ◽

Neuroprotective Effects

AbstractOur previous study demonstrated that gypenosides (Gp) exert protective effects on retinal nerve fibers and axons in a mouse model of experimental autoimmune optic neuritis. However, the therapeutic mechanisms remain unclear. Thus, in this study, a model of oxidative damage in retinal ganglion cells (RGCs) was established to investigate the protective effect of Gp, and its possible influence on oxidative stress in RGCs. Treatment of cells with H2O2 induced RGC injury owing to the generation of intracellular reactive oxygen species (ROS). In addition, the activities of antioxidative enzymes decreased and the expression of inflammatory factors increased, resulting in an increase in cellular apoptosis. Gp helped RGCs to become resistant to oxidation damage by directly reducing the amount of ROS in cells and exerting protective effects against H2O2-induced apoptosis. Treatment with Gp also reduced the generation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and increased nuclear respiratory factor 2 (Nrf-2) levels so as to increase the levels of heme oxygenase-1 (HO-1) and glutathione peroxidase 1/2 (Gpx1/2), which can enhance antioxidation in RGCs. In conclusion, our data indicate that neuroprotection by Gp involves its antioxidation and anti-inflammation effects. Gp prevents apoptosis through a mitochondrial apoptotic pathway. This finding might provide novel insights into understanding the mechanism of the neuroprotective effects of gypenosides in the treatment of optic neuritis.

Download Full-text

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7191856 ◽

2017 ◽

Vol 2017 ◽

pp. 1-15 ◽

Cited By ~ 7

Author(s):

Ziying Wang ◽

Zhuanli Zhou ◽

Xinbing Wei ◽

Mingwei Wang ◽

Bi-Ou Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Ischemia Reperfusion Injury ◽

Therapeutic Potential ◽

Ischemia Reperfusion ◽

The Novel ◽

Neuroprotective Effects ◽

Chemical Structures ◽

Cerebral Ischemia Reperfusion Injury ◽

Blood Brain Barrier Integrity

Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

Download Full-text

Flavonoids on diabetic nephropathy: advances and therapeutic opportunities

Chinese Medicine ◽

10.1186/s13020-021-00485-4 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Qichao Hu ◽

Caiyan Qu ◽

Xiaolin Xiao ◽

Wenwen Zhang ◽

Yinxiao Jiang ◽

...

Keyword(s):

Oxidative Stress ◽

Natural Products ◽

Diabetic Nephropathy ◽

Metabolic Diseases ◽

Inflammatory Responses ◽

The Body ◽

Diabetic Patients ◽

Public Attention ◽

Wide Range ◽

Tgf Β1

AbstractWith the advances in biomedical technologies, natural products have attracted substantial public attention in the area of drug discovery. Flavonoids are a class of active natural products with a wide range of pharmacological effects that are used for the treatment of several diseases, in particular chronic metabolic diseases. Diabetic nephropathy is a complication of diabetes with a particularly complicated pathological mechanism that affects at least 30% of diabetic patients and represents a great burden on public health. A large number of studies have shown that flavonoids can alleviate diabetic nephropathy. This review systematically summarizes the use of common flavonoids for the treatment of diabetic nephropathy. We found that flavonoids play a therapeutic role in diabetic nephropathy mainly by regulating oxidative stress and inflammation. Nrf-2/GSH, ROS production, HO-1, TGF-β1 and AGEs/RAGE are involved in the process of oxidative stress regulation. Quercetin, apigenin, baicalin, luteolin, hesperidin, genistein, proanthocyanidin and eriodictyol were found to be capable of alleviating oxidative stress related to the aforementioned factors. Regarding inflammatory responses, IL-1, IL-6β, TNF-α, SIRT1, NF-κB, and TGF-β1/smad are thought to be essential. Quercetin, kaempferol, myricetin, rutin, genistein, proanthocyanidin and eriodictyol were confirmed to influence the above targets. As a result, flavonoids promote podocyte autophagy and inhibit the overactivity of RAAS by suppressing the upstream oxidative stress and inflammatory pathways, ultimately alleviating DN. The above results indicate that flavonoids are promising drugs for the treatment of diabetic nephropathy. However, due to deficiencies in the effect of flavonoids on metabolic processes and their lack of structural stability in the body, further research is required to address these issues.

Download Full-text

Oxidative Stress, Antioxidant Defenses, COVID-19 and Pollution

Medical Research Archives ◽

10.18103/mra.v8i10.2254 ◽

2020 ◽

Vol 8 (10) ◽

Author(s):

Selva Rivas-Arancibia ◽

Jennifer Balderas-Miranda ◽

Lizbeth Belmont-Zúñiga ◽

Martín Martínez-Jáquez ◽

Eduardo Hernández-Orozco ◽

...

Keyword(s):

Oxidative Stress ◽

Trace Elements ◽

Immune System ◽

Inflammatory Response ◽

Inflammatory Responses ◽

The Body ◽

Antioxidant Defenses ◽

Cochrane Library ◽

Antioxidant Systems ◽

Low Levels

Patients with degenerative diseases present a chronic oxidative stress state, which puts them at a disadvantage when facing viral infections such as COVID-19. This is because there is a close relationship between redox signaling and this inflammatory response. Therefore, chronic changes in the redox balance cause alterations in the regulation of the immune system. An inflammatory response that must be reparative and self-limited loses its function and remains over time. In a chronic state of oxidative stress, there is a deficiency of antioxidants. This results in low levels of hormones, vitamins and trace elements, which are essential for the regulation of these systems. Furthermore, low levels of antioxidants imply a diminished capacity for a regulated inflammatory responses are much more vulnerable to a cytokine storm that mainly attacks the lungs, since they present a vicious circle between the null or diminished response of the antioxidant systems and the loss of regulation of the inflammatory process. Therefore, these patients are at a disadvantage in counteracting the response of defense systems to infection from SAR-COV19. A plausible option may be to restore the levels of Vitamins A, B, C, D, E and of essential trace elements such as manganese, selenium, zinc, in the body, which are key to either preventing or reducing the severity of the response of the immune system to the disease caused by SAR-CoV2. For the present review, we searched the specific sites of the Cochrane library database, PubMed and Medscape. The inclusion criteria were documents written in English or Spanish, published during the last 10 years.

Download Full-text

Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway

Journal of Immunology Research ◽

10.1155/2021/5151168 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Yajuan Lin ◽

Yunpeng Xie ◽

Zhujing Hao ◽

Hailian Bi ◽

Yang Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Uric Acid ◽

Nuclear Translocation ◽

Density Lipoprotein ◽

Endothelial Damage ◽

The Body ◽

Inflammatory Factors ◽

Cell Phenotype ◽

Mrna Levels

Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.

Download Full-text

Ginsenoside-Rg1 Rescues Stress-Induced Depression-Like Behaviors via Suppression of Oxidative Stress and Neural Inflammation in Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2325391 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Ye Li ◽

Liyan Wang ◽

Peng Wang ◽

Cuiqin Fan ◽

Ping Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Neuronal Damage ◽

Present Report ◽

Mild Stress ◽

Ginsenoside Rg1 ◽

Neuroprotective Effects ◽

Related Condition ◽

Antioxidant Stress

Depression is an inflammatory-related condition, with the progression in neuronal damage resulting in major depression disorder. Ginsenoside-Rg1, a sterol extract from the herb Panax ginseng, has been shown to exert neuroprotective effects upon neurodegeneration disorders. However, whether ginsenoside-Rg1 confers antidepressant-like effects on neuroinflammation as associated with depression, as well as the possible mechanism involved in these neuroprotective effects, is currently unclear. In the present report, we show that treatment with ginsenoside-Rg1 (40 mg/kg, i.p.) significantly ameliorated depressive-like behaviors as induced by chronic unpredictable mild stress (CUMS) in a rat model of depression. Moreover, these CUMS rats treated with ginsenoside-Rg1 showed reductions in the levels of the oxidative stress products and the activity in the antioxidant stress kinase. Furthermore, CUMS rats treated with ginsenoside-Rg1 showed ameliorated neuroinflammation and associated neuronal apoptosis along with a reduction in dendritic spine atrophy and display of depressive behaviors. Taken together, the results of this study suggest that ginsenoside-Rg1 produces antidepressant-like effects in CUMS-exposed rats; and one of the mechanisms for these antidepressant-like effects of ginsenoside-Rg1 appears to involve protection against oxidative stress and thus the neuronal deterioration resulting from inflammatory responses. These findings provide evidence for the therapeutic potential of ginsenoside-Rg1 in the treatment of stress-related depression.

Download Full-text

Progress in Research on the Mechanism and Treatment of Post-stroke Infection

Infection International ◽

10.1515/ii-2017-0134 ◽

2016 ◽

Vol 5 (3) ◽

pp. 69-74

Author(s):

Hongtao Zhang

Keyword(s):

Immune System ◽

Inflammatory Responses ◽

The Body ◽

Main Mechanism ◽

Inflammatory Factors ◽

Stroke Patients ◽

Lesion Area ◽

Peripheral Immune System ◽

Post Stroke ◽

Stroke Center

AbstractPost-stroke infection hinders the recovery of stroke patients and can even cause death. The main mechanism of post-stroke infection is related with the post-stroke center, the activation of the peripheral immune system, and the release of inflammatory factors caused by the lesion area and pathophysiological changes in the body. Therefore, elucidating the body’s abnormal immune inflammatory responses after stroke is crucial for the prevention, treatment, and alleviation of post-stroke infection.

Download Full-text

PO-205 Effect of AMPK agonist / inhibitor on Nrf2 expression in C2C12 cells

Exercise Biochemistry Review ◽

10.14428/ebr.v1i5.8983 ◽

2018 ◽

Vol 1 (5) ◽

Author(s):

Lin Luo ◽

Ying Zhang

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Stress Response ◽

Energy Metabolism ◽

The Body ◽

C2c12 Cells ◽

Control Group ◽

Compound C ◽

Antioxidant Stress ◽

Nrf2 Expression

Objective In the past few decades, the study of skeletal muscle oxidative stress has been concerned about the increase of free radicals induced by muscle contraction. In recent years, the activation of antioxidant stress signaling pathway has gradually become one of the hot topics in the field of sports medicine. Although current research has confirmed that long-term aerobic training can bring health benefits to the body, the molecular mechanism of its role is still not very clear.Traditionally, AMPK has been regarded as the energy receptor of cells. During exercise, the energy consumption of skeletal muscle doubled, ATP decreased, AMP increased, and the ratio of AMP/ATP increased, thus inducing the activation of AMPK and regulating cell energy metabolism. Recent studies have found that AMPK not only plays an important role in the regulation of energy metabolism, but also plays a role in the body's antioxidant stress response. However, the relationship between AMPK and oxidative stress has been studied only in a small number of cells in non skeletal muscle cells. The results of this few studies show that oxidative stress in AMPK can not depend on the increase of intracellular AMP/ATP ratio, and the independent activation of AMPK, thus reducing the level of intracellular ROS, but the molecular mechanism of its action is not clear. Nrf2 is an important nuclear transcription factor in the body and plays an important role in the body's antioxidant stress response. Whether AMPK can participate in the regulation of Nrf2 mediated antioxidant activity in skeletal muscle has not been reported.In this study, the mouse skeletal muscle C2C12 cells were used in vitro cell experiments. The AMPK pharmacologic activator AICAR and the pharmacological inhibitor Compound C were used to treat the cells respectively. The role of AMPK in the regulation of Nrf2 expression in C2C12 cells and its mechanism were observed. Methods Cell experiments were performed on C2C12 cells of skeletal muscle of mice, and AMPK activator AICAR and AMPK inhibitor Compound C were used to intervene. The fluorescence intensity of C2C12 cells in each group was qualitatively detected by fluorescence inverted microscope, and the ROS level of C2C12 cells in each group was detected by fluorescence colorimetry. Results the ROS level of each group was significantly higher than that of the control group. RT-PCR assay was used to detect the antioxidant enzyme mRNA level of C2C12 cells in each group. Western Blot assay was used to detect the expression of AMPK alpha, pAMPK alpha, Nrf2, pNrf2 and antioxidant enzyme protein in C2C12 cells of each group. Results (1) compared with the control group, the pAMPK alpha /AMPK alpha ratio of C2C12 cells in the agonist group increased significantly, the expression of pNrf2 protein in the cells increased significantly, and the expression of NQO1mRNA, HO-1mRNA and GSR mRNA increased significantly, and the cells SOD1, GCLM, NQO1, HO-1, pNrf2, and protein were significantly increased. Low. (2) compared with the control group, the levels of NQO1mRNA, HO-1mRNA, CATmRNA, SOD1mRNA, Gpx-1mRNA and GCLc mRNA in the C2C12 cells of the inhibitor group decreased significantly, and the expression of NQO1 and GCLM proteins in the cells decreased significantly, and the ROS level of the cells increased significantly. Conclusions  (1) the activation of AMPK by AICAR activates the increase of Nrf2 activation in skeletal muscle C2C12 cells, and then increases the expression of mRNA and protein (SOD1, GCLM, NQO1, NQO1, GSR) in the downstream of Nrf2 (NQO1, HO-1, GSR), and significantly reduces the intracellular level.(2) the inhibition of AMPK by Compound C significantly decreased the mRNA expression of C2C12 cells (NQO1, HO-1, CAT, SOD1, Gpx-1, GCLc) in skeletal muscle, and significantly decreased the expression of protein (NQO1 and GCLc)

Download Full-text

Beneficial effects of Spirogyra Neglecta Extract on antioxidant and anti-inflammatory factors in streptozotocin-induced diabetic rats

10.1101/485219 ◽

2018 ◽

Author(s):

Behzad Mesbahzadeh ◽

Seyed Ali Rajaei ◽

Parnia Tarahomi ◽

Seyed Ali Seyedinia ◽

Mehrnoush Rahmani ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Total Antioxidant Status ◽

Serum Levels ◽

Diabetic Control ◽

Diabetic Rats ◽

Inflammatory Factors ◽

Tnf Alpha ◽

Serum Concentrations ◽

Necrosis Factor Alpha

Objectives: This study was conducted to evaluate the effects of oral supplementation of Spirogyra algae on oxidative damages and inflammatory responses in streptozotocin (STZ)-induced diabetic rats. Methods: Diabetes was induced by administration of 55 mg/kg of streptozotocin. A total of sixty-four rats were divided into eight groups of eight rats each as follows:1) non-diabetic control; 2, 3, and 4) non-diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae/kg/d; 5) control diabetic; and 6, 7, and 8) diabetic rats treated with 15, 30, and 45 mg of Spirogyra algae extract. At the end of the trial, the serum concentrations of glucose, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), malondialdehyde (MDA), glutathione (GSH), total antioxidant status (TAS), C-reactive protein (CRP), insulin, triglycerides, and cholesterol were examined by specified procedures. Results: Our findings indicated that the administration of STZ significantly increased the serum concentrations of glucose, triglycerides, cholesterol, CRP, IL-6, TNF-alpha), and MDA and decreased the serum levels of GSH and TAS (P<0.05) in diabetic rats. Oral administration of Spirogyra alleviated adverse effects of diabetes on oxidative stress and inflammatory factors in diabetic rats (P<0.05). Conclusion: It can be stated that Spirogyra algae extract can be used for treatment of diabetes likely due to prevention of oxidative stress and alleviation of inflammation in the rat model.

Download Full-text