scholarly journals Guanxintai Exerts Protective Effects on Ischemic Cardiomyocytes by Mitigating Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jing Yang ◽  
Weiju Sun ◽  
Junfeng Sun ◽  
Fengyue Wang ◽  
Yuling Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serum Lipid ◽  
Antioxidative Activity ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Myocardial Apoptosis ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

Oxidative stress participates in numerous myocardial pathophysiological processes and is considered a therapeutic target for myocardial ischemia and heart failure. Guanxintai (GXT), a traditional Chinese medicine, is commonly used to treat cardiovascular disease on account of its numerous beneficial physiological activities, such as dilating coronary arteries, inhibiting platelet aggregation, and reducing the serum lipid content. However, the antioxidative properties of GXT and potential underlying mechanisms remain to be established. In the present study, we investigated the protective effects of GXT on ischemic cardiomyocytes and the associated antioxidative mechanisms, both in vivo and in vitro. Notably, GXT treatment reduced the degree of cardiomyocyte injury, myocardial apoptosis, and fibrosis and partially improved cardiac function after myocardial infarction. Furthermore, GXT suppressed the level of ROS as well as expression of NADPH oxidase (NOX) and phospho-p38 mitogen-activated protein kinase (MAPK) proteins. Our results collectively suggest that the protective effects of GXT on ischemic cardiomyocytes are exerted through its antioxidative activity of NOX inhibition.

Aloe Metabolites Prevent LPS-Induced Sepsis and Inflammatory Response by Inhibiting Mitogen-Activated Protein Kinase Activation

2017 ◽  
Vol 45 (04) ◽  
pp. 847-861 ◽  
Author(s):  
Chia-Yang Li ◽  
Katsuhiko Suzuki ◽  
Yung-Li Hung ◽  
Meng-Syuan Yang ◽  
Chung-Ping Yu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aloe Vera ◽  
Peritoneal Macrophages ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Raw264.7 Macrophages ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Aloe, a polyphenolic anthranoid-containing Aloe vera leaves, is a Chinese medicine and a popular dietary supplement worldwide. In in vivo situations, polyphenolic anthranoids are extensively broken down into glucuronides and sulfate metabolites by the gut and the liver. The anti-inflammatory potential of aloe metabolites has not been examined. The aim of this study was to investigate the anti-inflammatory effects of aloe metabolites from in vitro (lipopolysaccharides (LPS)-activated RAW264.7 macrophages) and ex vivo (LPS-activated peritoneal macrophages) to in vivo (LPS-induced septic mice). The production of proinflammatory cytokines (TNF-[Formula: see text] and IL-12) and NO was determined by ELISA and Griess reagents, respectively. The expression levels of iNOS and MAPKs were analyzed by Western blot. Our results showed that aloe metabolites inhibited the expression of iNOS, decreased the production of TNF-[Formula: see text], IL-12, and NO, and suppressed the phosphorylation of MAPKs by LPS-activated RAW264.7 macrophages. In addition, aloe metabolites reduced the production of NO, TNF-[Formula: see text] and IL-12 by murine peritoneal macrophages. Furthermore, aloe administration significantly reduced the NO level and exhibited protective effects against sepsis-related death in LPS-induced septic mice. These results suggest that aloe metabolites exerted anti-inflammatory effects in vivo, and that these effects were associated with the inhibition of inflammatory mediators. Therefore, aloe could be considered an effective therapeutic agent for the treatment of sepsis.

scholarly journals Daphnetin Attenuated Cisplatin-Induced Acute Nephrotoxicity With Enhancing Antitumor Activity of Cisplatin by Upregulating SIRT1/SIRT6-Nrf2 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoye Fan ◽  
Wei Wei ◽  
Jingbo Huang ◽  
Liping Peng ◽  
Xinxin Ci
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Damage ◽  
Protective Effects ◽  
Normal Tissues ◽  
Nrf2 Signaling Pathway ◽  
Apoptosis Pathways ◽  
Underlying Mechanisms

Cisplatin (CDDP) is a widely used drug for cancer treatment that exhibits major side effects in normal tissues, such as nephrotoxicity in kidneys. The Nrf2 signaling pathway, a regulator of mitochondrial dysfunction, oxidative stress and inflammation, is a potential therapeutic target in CDDP-induced nephrotoxicity. We explored the underlying mechanisms in wild-type (WT) and Nrf2−/− mice on CDDP-induced renal dysfunction in vivo. We found that Nrf2 deficiency aggravated CDDP-induced nephrotoxicity, and Daph treatment significantly ameliorated the renal injury characterized by biochemical markers in WT mice and reduced the CDDP-induced cell damage. In terms of the mechanism, Daph upregulated the SIRT1 and SIRT6 expression in vivo and in vitro. Furthermore, Daph inhibited the expression level of NOX4, whereas it activated Nrf2 translocation and antioxidant enzymes HO-1 and NQO1, and alleviated oxidative stress and mitochondrial dysfunction. Moreover, Daph suppressed CDDP-induced NF-κB and MAPK inflammation pathways, as well as p53 and cleaved caspase-3 apoptosis pathways. Notably, the protective effects of Daph in WT mice were completely abrogated in Nrf2−/− mice. Moreover, Daph enhanced, rather than attenuated, the tumoricidal effect of CDDP.

scholarly journals Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Jing Sun ◽  
Guibo Sun ◽  
Xiaolan Cui ◽  
Xiangbao Meng ◽  
Meng Qin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Damage ◽  
Mitochondrial Apoptosis ◽  
Mechanism Study ◽  
Apoptosis Pathway ◽  
Mitochondrial Apoptosis Pathway ◽  
Myocardial Apoptosis ◽  
Underlying Mechanisms

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark ofMyrica rubra, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

scholarly journals Chinese herbal formulas for postmenopausal osteoporosis: A review of preclinical evidence on animal studies and molecular mechanism

2018 ◽  
Vol 01 (02) ◽  
pp. 75-83
Author(s):  
Jing Lin ◽  
Tian Lv ◽  
Fubo Tian ◽  
Yan Wang ◽  
Mingyan Wang ◽  
...  
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Animal Studies ◽  
Mitogen Activated Protein Kinase ◽  
Chinese Herbal ◽  
Morphogenetic Protein ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

Whether Chinese herbal formulas are effective in treatment of postmenopausal osteoporosis remains unclear. The aim of this study is to explore the experimental evidence of both in vitro and in vivo preclinical studies using Chinese herbal formulas in postmenopausal osteoporosis. Searches were applied to various databases with relevant keywords. Original in vivo and in vitro studies using Chinese herbal formulas to treat postmenopausal osteoporosis, and with full text available, were included. Er-Xian Decoction, Bu-Shen-Ning-Xin Decoction, Qing E Formula, Liuwei Dihuang Wan, and Xian-Ling-Gu-Bao Decoction, the most commonly studied formulas, were selected from the pool of Chinese medicine. The preclinical data indicated the potential use of Chinese herbal formulas in postmenopausal osteoporosis. The underlying mechanisms included bone morphogenetic protein (BMP), Wnt/[Formula: see text]-catenin, extracellular-signal-regulated kinase/c-Jun [Formula: see text] terminal kinase/mitogen-activated protein kinase (ERK/JNK/MAPK), estrogen receptor (ER), and osteoprotegerin/receptor activator of nuclear factor [Formula: see text]B ligand (OPG/RANKL) signaling pathways. This study demonstrated the anti-osteoporotic effect of Chinese herbal formulas targeting different pathways in bone metabolism. Further study with adequate sample size and follow-up time, appropriate controls, and optimal blinding is required.

scholarly journals Protective Effects of Salidroside against Carbon Tetrachloride (CCl4)-Induced Liver Injury by Initiating Mitochondria to Resist Oxidative Stress in Mice

2019 ◽  
Vol 20 (13) ◽  
pp. 3187 ◽  
Author(s):  
Shi-Yu Lin ◽  
Xu Dan ◽  
Xia-Xia Du ◽  
Chong-Lin Ran ◽  
Xu Lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Tetrachloride ◽  
Protein Kinase ◽  
Liver Injury ◽  
Liver Steatosis ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Mitogen Activated Protein ◽  
And Function

The antioxidant effect of salidroside has been proven, but its role in liver injury is poorly understood. In this study, we aimed to evaluate the protective effects and mechanism of salidroside on liver injury induced by carbon tetrachloride (CCl4) in vivo. Mice were pretreated with salidroside (60 mg/kg, intraperitoneally injected, i.p.) once per day for 14 consecutive days and then administered with CCl4 (15.95 g/kg, i.p.) for 24 h to produce a liver injury model. Salidroside attenuated hepatic transaminase elevation in serum and ameliorated liver steatosis and necrosis, thereby suggesting its protective effect on the liver. Salidroside antagonized CCl4-induced toxicity by equilibrating antioxidation system, thereby inhibiting reactive oxygen species accumulation, and restoring mitochondrial structure and function. Salidroside exerts antioxidant and liver-protective effects by selectively inhibiting the activation of genes, including growth arrest and DNA -damage-inducible 45 α (Gadd45a), mitogen-activated protein kinase 7 (Mapk7), and related RAS viral oncogene homolog 2 (Rras2), which induce oxidative stress in the mitogen-activated protein kinase pathway. These results revealed that salidroside can protect the liver from CCl4-induced injury by resisting oxidative stress and protecting mitochondrial function.

scholarly journals Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wanchen Ning ◽  
Simin Li ◽  
Jokyab Tsering ◽  
Yihong Ma ◽  
Honghong Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activities ◽  
Cell Model ◽  
Neuroprotective Effect ◽  
Flow Cytometric Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Zebrafish Model

Background. Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods. An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results. The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. Conclusion. In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

scholarly journals Role for the Ran Binding Protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 Signal Transduction

2004 ◽  
Vol 3 (6) ◽  
pp. 1544-1556 ◽  
Author(s):  
Jade Mei-Yeh Lu ◽  
Robert J. Deschenes ◽  
Jan S. Fassler
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
Osmotic Stress ◽  
Kinase Activity ◽  
Mitogen Activated Protein Kinase ◽  
Osmotic Response ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

ABSTRACT Yeast Sln1p is an osmotic stress sensor with histidine kinase activity. Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions. Many aspects of Sln1 function, such as how kinase activity is regulated to allow a rapid response to the continually changing osmotic environment, are not understood. To gain insight into Sln1p function, we conducted a two-hybrid screen to identify interactors. Mog1p, a protein that interacts with the yeast Ran1 homolog, Gsp1p, was identified in this screen. The interaction with Mog1p was characterized in vitro, and its importance was assessed in vivo. mog1 mutants exhibit defects in SLN1-SKN7 signal transduction and mislocalization of the Skn7p transcription factor. The requirement for Mog1p in normal localization of Skn7p to the nucleus does not fully account for the mog1-related defects in SLN1-SKN7 signal transduction, raising the possibility that Mog1p may play a role in Skn7 binding and activation of osmotic response genes.

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