scholarly journals Psoralea corylifolia L. Seed Extract Attenuates Methylglyoxal-Induced Insulin Resistance by Inhibition of Advanced Glycation End Product Formation

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Cao-Sang Truong ◽  
Eunhui Seo ◽  
Hee-Sook Jun
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Product Formation ◽  
The Body ◽  
Psoralea Corylifolia ◽  
Advanced Glycation ◽  
Metabolic Conditions

Accumulation of advanced glycation end products (AGEs) in the body has been implicated in the pathogenesis of metabolic conditions, such as diabetes mellitus. Methylglyoxal (MGO), a major precursor of AGEs, has been reported to induce insulin resistance in both in vitro and in vivo studies. Psoralea corylifolia seeds (PCS) have been used as a traditional medicine for several diseases, but their potential application in treating insulin resistance has not yet been evaluated. This study is aimed at investigating whether PCS extract could attenuate insulin resistance induced by MGO. Male C57BL/6N mice (6 weeks old) were administered 1% MGO in their drinking water for 18 weeks, and the PCS extract (200 or 500 mg/kg) was orally administered daily from the first day of the MGO administration. We observed that both 200 and 500 mg/kg PCS extract treatment significantly improved glucose tolerance and insulin sensitivity and markedly restored p-Akt and p-IRS1/2 expression in the livers of the MGO-administered mice. Additionally, the PCS extract significantly increased the phosphorylation of Akt and IRS-1/2 and glucose uptake in MGO-treated HepG2 cells. Further studies showed that the PCS extract inhibited MGO-induced AGE formation in the HepG2 cells and in the sera of MGO-administered mice. PCS extract also increased the expression of glyoxalase 1 (GLO1) in the liver tissue of MGO-administered mice. The PCS extract significantly decreased the phosphorylation of ERK, p38, and NF-κB and suppressed the mRNA expression of proinflammatory molecules including TNF-α and IL-1β and iNOS in MGO-administered mice. Additionally, we demonstrated that the PCS extract attenuated oxidative stress, as evidenced by the reduced ROS production in the MGO-treated cells and the enhanced expression of antioxidant enzymes in the liver of MGO-administered mice. Thus, PCS extract ameliorated the MGO-induced insulin resistance in HepG2 cells and in mice by reducing oxidative stress via the inhibition of AGE formation. These findings suggest the potential of PCS extract as a candidate for the prevention and treatment of insulin resistance.

scholarly journals DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells

2022 ◽  
Vol 12 ◽  
Author(s):  
Xuguang Zhang ◽  
Yuxin Zhang ◽  
Mingyan Zhou ◽  
Yiqiang Xie ◽  
Xiujuan Dong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
High Glucose ◽  
Hepg2 Cells ◽  
Fasting Blood Glucose ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Alpinia Officinarum

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

scholarly journals Honokiol Alleviates Methionine-Choline Deficient Diet-Induced Hepatic Steatosis and Oxidative Stress in C57BL/6 Mice by Regulating CFLAR-JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ting Zhai ◽  
Wei Xu ◽  
Yayun Liu ◽  
Kun Qian ◽  
Yanling Xiong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Regulatory Gene ◽  
Deficient Diet ◽  
Jnk Pathway ◽  
Beneficial Effects ◽  
Protein Levels ◽  
And Oxidative Stress

Background. Honokiol (HNK) has been reported to possess various beneficial effects in the context of metabolic disorders, including fatty liver, insulin resistance, and oxidative stress which are closely related to nonalcoholic steatohepatitis (NASH), however with no particular reference to CFLAR or JNK. Methods. C57BL/6 mice were fed methionine-choline-deficient (MCD) diet and administered simultaneously with HNK (10 and 20 mg/kg once a day, ig) for 6 weeks, and NCTC1469 cells were pretreated, respectively, by oleic acid (OA, 0.5 mmol/L) plus palmitic acid (PA, 0.25 mmol/L) for 24 h, and adenovirus-down Cflar for 24 h, then exposed to HNK (10 and 20 μmol/L) for 24 h. Commercial kits, H&E, MT, ORO staining, RT-qPCR, and Western blotting were used to detect the biomarkers, hepatic histological changes, and the expression of key genes involved in NASH. Results. The in vivo results showed that HNK suppressed the phosphorylation of JNK (pJNK) by activating CFLAR; enhanced the mRNA expression of lipid metabolism-related genes Acox, Cpt1α, Fabp5, Gpat, Mttp, Pparα, and Scd-1; and decreased the levels of hepatic TG, TC, and MDA, as well as the levels of serum ALT and AST. Additionally, HNK enhanced the protein expression of oxidative stress-related key regulatory gene NRF2 and the activities of antioxidases HO-1, CAT, and GSH-Px and decreased the protein levels of prooxidases CYP4A and CYP2E1. The in vivo effects of HNK on the expression of CLFAR, pJNK, and NRF2 were proved by the in vitro experiments. Moreover, HNK promoted the phosphorylation of IRS1 (pIRS1) in both tested cells and increased the uptake of fluorescent glucose 2-NBDG in OA- and PA-pretreated cells. Conclusions. HNK ameliorated NASH mainly by activating the CFLAR-JNK pathway, which not only alleviated fat deposition by promoting the efflux and β-oxidation of fatty acids in the liver but also attenuated hepatic oxidative damage and insulin resistance by upregulating the expression of NRF2 and pIRS1.

scholarly journals Mulberry Anthocyanin Extract Ameliorates Oxidative Damage in HepG2 Cells and Prolongs the Lifespan of Caenorhabditis elegans through MAPK and Nrf2 Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Fujie Yan ◽  
Yushu Chen ◽  
Ramila Azat ◽  
Xiaodong Zheng
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Hepg2 Cells ◽  
Insulin Signalling ◽  
Glucose Consumption ◽  
Redox Status ◽  
C Elegans ◽  
Beneficial Effects

Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation. In vivo, extended lifespan was observed in C. elegans damaged by paraquat in the presence of MAE, while these beneficial effects were disappeared in pmk-1 and daf-16 mutants. PMK-1 and SKN-1 were activated after exposure to paraquat and MAE suppressed PMK-1 activation but enhanced SKN-1 stimulation. Our findings suggested that MAE recovered redox status in HepG2 cells and C. elegans that suffered from oxidative stress, which might be by targeting MAPKs and Nrf2.

Glucose oxidase induces insulin resistance via influencing multiple targets in vitro and in vivo: The central role of oxidative stress

Biochimie ◽  
2012 ◽  
Vol 94 (8) ◽  
pp. 1705-1717 ◽  
Author(s):  
Xin Wang ◽  
Chunshan Gu ◽  
Wei He ◽  
Xiaolong Ye ◽  
Hongli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Glucose Oxidase ◽  
Multiple Targets

scholarly journals Antioxidant Activity of Pigmented Rice and Impact on Health

JURNAL PANGAN ◽  
2019 ◽  
Vol 28 (1) ◽  
pp. 11-22
Author(s):  
Arfina Sukmawati Arifin
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Antioxidant Activity ◽  
Vascular Function ◽  
Healthy Lifestyle ◽  
Cell Damage ◽  
The Body ◽  
Food Sources

The high number of free radicals that are not balanced with the amount of antioxidants in the body triggers oxidative stress. Oxidative stress causes impaired vascular function, damage to proteins and lipids in membrane cell, and nucleic acid (DNA) mutations. Chronic cell damage has a negative effect on tissue that triggers various diseases such as neurodegenerative diseases (Alzheimer's, Parkinson's), cardiovascular diseases (hypertension, arteriosclerosis, and others), cataracts, retinal damage, maculopathy, rheumatoid arthritis, asthma, stroke, diabetes mellitus , immunodepression, cancer, aging, hyperoxia, dermatitis, and others. The application of a healthy lifestyle for example by consuming food sources of bioactive compounds can minimize health risks. Rice is the staple food of the Indonesian people. Some types of rice contain red and black pigments which are known to have high antioxidant activity compared to white rice. The pigment comes from anthocyanin and proanthocyanidin. Various studies in vitro and in vivo prove that anthocyanin and proantocyanidine act as antioxidants and potency as a preventative for various diseases such as cardiovascular, diabetes mellitus, and etc.

scholarly journals SIRT3-dependent mitochondrial oxidative stress in sodium fluoride-induced hepatotoxicity and salvage by melatonin

2017 ◽  
Author(s):  
Chao Song ◽  
Jiamin Zhao ◽  
Jingcheng Zhang ◽  
Tingchao Mao ◽  
Beibei Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepg2 Cells ◽  
Binding Activity ◽  
Daily Injection ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Peroxisome Proliferator Activated Receptor

AbstractOxidative stress induced by fluoride (F) is associated with fluorosis formation, but the underlying molecular mechanism remains unclear. In this study, Melatonin pretreatment suppressed F-induced hepatocyte injury in HepG2 cells. Melatonin increases the activity of superoxide dismutase (SOD2) by enhancing sirtuin 3 (SIRT3)-mediated deacetylation and promotes SOD2 gene expression via SIRT3-regulated DNA-binding activity of forkhead box O3 (FoxO3a), indicating that melatonin markedly enhanced mROS scavenging in F-exposed HepG2 cells. Notably, melatonin activated the peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α). PGC-1α interacted with the estrogen-related receptor alpha (ERRα) bound to the SIRT3 promoter, where it functions as a transcription factor to regulate SIRT3 expression. Furthermore, daily injection of melatonin for 30 days inhibited F-induced oxidative stress in mice liver, leading to improvement of liver function. Mechanistic study revealed that the protective effects of melatonin were associated with down-regulation of JNK1/2 phosphorylation in vitro and in vivo. Collectively, our data suggest a novel role of melatonin in preventing F-induced oxidative stress through activation of the SIRT3 pathway.

scholarly journals The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1339
Author(s):  
Ching-Chi Chang ◽  
Hsin-Hua Li ◽  
Sing-Hua Tsou ◽  
Hui-Chih Hung ◽  
Guang-Yaw Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Stem Cell ◽  
Amyloid Β ◽  
Protective Effects ◽  
Mitochondrial Superoxide ◽  
Nanog Expression ◽  
Pluripotency Factor

Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aβ-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aβ-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog—both in vitro and in vivo—and investigated the protective effects and underlying mechanisms against Aβ. We found that overexpression of Nanog is responsible for attenuating Aβ-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aβ neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aβ, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aβ neurotoxicity in the AD brain.

scholarly journals Inhibition of advanced glycation end-product formation on eye lens protein by rutin

2011 ◽  
Vol 107 (7) ◽  
pp. 941-949 ◽  
Author(s):  
P. Muthenna ◽  
C. Akileshwari ◽  
Megha Saraswat ◽  
G. Bhanuprakash Reddy
Keyword(s):  
Product Formation ◽  
Protein Glycation ◽  
Eye Lens ◽  
Lens Protein ◽  
Advanced Glycation ◽  
Mechanism Of Inhibition ◽  
Eye Lens Protein ◽  
Herbs And Spices

Formation of advanced glycation end products (AGE) plays a key role in the several pathophysiologies associated with ageing and diabetes, such as arthritis, atherosclerosis, chronic renal insufficiency, Alzheimer's disease, nephropathy, neuropathy and cataract. This raises the possibility of inhibition of AGE formation as one of the approaches to prevent or arrest the progression of diabetic complications. Previously, we have reported that some common dietary sources such as fruits, vegetables, herbs and spices have the potential to inhibit AGE formation. Flavonoids are abundantly found in fruits, vegetables, herbs and spices, and rutin is one of the commonly found dietary flavonols. In the present study, we have demonstrated the antiglycating potential and mechanism of action of rutin using goat eye lens proteins as model proteins. Under in vitro conditions, rutin inhibited glycation as assessed by SDS-PAGE, AGE-fluorescence, boronate affinity chromatography and immunodetection of specific AGE. Further, we provided insight into the mechanism of inhibition of protein glycation that rutin not only scavenges free-radicals directly but also chelates the metal ions by forming complexes with them and thereby partly inhibiting post-Amadori formation. These findings indicate the potential of rutin to prevent and/or inhibit protein glycation and the prospects for controlling AGE-mediated diabetic pathological conditions in vivo.

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