The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes

AMP kinase (AMPK) plays an important role in the regulation of energy metabolism in cardiac cells. Furthermore, activation of AMPK protects the heart from myocardial infarction and heart failure. The present study examines whether or not AMPK affects the peroxisome proliferator-activated receptor-α (PPARα)/mitochondria pathway in response to acute oxidative stress in cultured cardiomyocytes. Cultured H9c2 rat embryonic cardioblasts were exposed to H2O2-induced acute oxidative stress in the presence or absence of metformin, compound C (AMPK inhibitor), GW6471 (PPARα inhibitor), or A-769662 (AMPK activator). Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death. In addition, metformin attenuated reactive oxygen species generation and depolarization of the inner mitochondrial membrane. The antioxidative effects of metformin were associated with the prevention of mitochondrial DNA damage in cardiomyocytes. Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARα and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation. The beneficial effects of metformin were not due to acetylation or phosphorylation of PPARα in response to oxidative stress. In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARα-CypD interactions, independent of phosphorylation and acetylation of PPARα and CypD.

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Notoginsenoside R1 Ameliorates Diabetic Retinopathy through PINK1-Dependent Activation of Mitophagy

Cells ◽

10.3390/cells8030213 ◽

2019 ◽

Vol 8 (3) ◽

pp. 213 ◽

Cited By ~ 15

Author(s):

Ping Zhou ◽

Weijie Xie ◽

Xiangbao Meng ◽

Yadong Zhai ◽

Xi Dong ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Oral Treatment ◽

Müller Cells ◽

Panax Notoginseng ◽

Protective Effects ◽

Muller Cells ◽

Beneficial Effects ◽

Pre Treatment ◽

Lc3 Puncta

: Accumulating evidence has indicated that inflammation, oxidative stress, apoptosis, and autophagy in retinal Müller cells are involved in diabetic retinopathy (DR). Notoginsenoside R1 (NGR1), a novel saponin extracted from Panax notoginseng, posesses pharmacological properties, including treating diabetic encephalopathy and improving microcirculatory disorders. Nevertheless, its beneficial effects on DR and the potential mechanism remain to be elucidated. In this study, we found retinal vascular degeneration, reduced retinal thickness, and impaired retinal function in db/db mice were all dramatically attenuated by oral treatment with NGR1 (30 mg/kg) for 12 weeks. NGR1 pretreatment also significantly inhibited apoptosis, markedly suppressed the VEGF expression, markedly increased PEDF expression and markedly inhibited oxidative stress and inflammation in rat retinal Müller cells (rMC-1) subjected to high glucose (HG) and in the retinas of db/db mice. Furthermore, NGR1 pre-treatment upregulated the level of PINK1 and Parkin, increased the LC3-II/LC3-I ratio, and downregulated the level of p62/SQSTM1 in rMC-1 cells induced by HG and in the retinas of db/db mice. Moreover, NGR1 administration enhanced the co-localization of GFP-LC3 puncta and MitoTracker in rMC-1 cells. Importantly, knockdown of PINK1 abolished the protective effects of NGR1. In conclusion, these phenomena suggested that NGR1 prevented DR via PINK1-dependent enhancement of mitophagy.

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Crocin Improves Insulin Sensitivity and Ameliorates Adiposity by Regulating AMPK-CDK5-PPARγ Signaling

BioMed Research International ◽

10.1155/2020/9136282 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Kai Fang ◽

Ming Gu

Keyword(s):

Protein Level ◽

Biological Activities ◽

Protective Effects ◽

Metabolic Dysfunction ◽

Ampk Activation ◽

Diabetic Mice ◽

Wild Type ◽

Ampk Signaling ◽

Beneficial Effects

Crocin is a carotenoid compound which possesses multiple biological activities. Our and other laboratory’s previous findings show that crocin alleviates obesity and type 2 diabetes-related complications. We have found that crocin activates AMP-activated protein kinase (AMPK) signaling and inhibition of AMPK suppresses crocin-induced protective effects. However, the causal role of AMPK activation in the biological role of crocin is still not verified. In the present study, we showed that crocin markedly inhibits the changes of glucose metabolic parameters and serum lipid profiles in wild type diabetic mice. In AMPKα KO diabetic mice, those protective effects of crocin against glucose and lipid metabolic dysfunction were abolished. These results demonstrated AMPK activation was responsible for the beneficial effects of crocin on metabolic dysfunction. Moreover, we have shown that the antiobese effect of crocin has been abolished by the deficiency of AMPKα. We also showed that crocin induced a significant decrease of CDK5 protein level in wild type diabetic mice, while this effect was abolished in AMPKα KO diabetic mice. The regulation of downstream targets of CDK5/PPARγ by crocin was abolished by the deficiency of AMPK. In conclusion, our study verified that activation of AMPK is involved in crocin-induced protective effects against glucose and lipid metabolic dysfunction. Activation of AMPK downregulates the protein level of CDK5, followed by the decrease of PPARγ phosphorylation, leading to the inhibition of adipose formation and metabolic dysfunction. Our study provides new insights into the mechanism of protective effects of crocin and interaction of AMPK and CDK5/PPARγ signaling.

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Dehydroepiandrosterone Prevents H2O2-Induced BRL-3A Cell Oxidative Damage through Activation of PI3K/Akt Pathways rather than MAPK Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/2985956 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14

Author(s):

Longlong Li ◽

Yao Yao ◽

Zhihao Jiang ◽

Jinlong Zhao ◽

Ji Cao ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Signaling Pathways ◽

Hormone Receptors ◽

Mapk Signaling ◽

Ros Generation ◽

Protective Effects ◽

Pi3k Inhibitor Ly294002 ◽

Beneficial Effects

Dehydroepiandrosterone (DHEA) is a popular dietary supplement that has well-known benefits in animals and humans, but there is not enough information about the mechanisms underlying its effects. The present study aimed at investigating these mechanisms through in vitro experiments on the effects of DHEA on rat liver BRL-3A cells exposed to oxidative stress through H2O2. The findings showed that DHEA increased the antioxidant enzyme activity, decreased ROS generation, and inhibited apoptosis in H2O2-treated cells. These effects of DHEA were not observed when the cells were pretreated with known antagonists of sex hormones (Trilostane, Flutamide, or Fulvestrant). Furthermore, treatment with estradiol and testosterone did not have the same protective effects as DHEA. Thus, the beneficial effects of DHEA were associated with mechanisms that were independent of steroid hormone pathways. With regard to the mechanism underlying the antiapoptotic effect of DHEA, pretreatment with DHEA was found to induce a significant decrease in the protein expression of Bax and caspase-3 and a significant increase in the protein expression of PI3K and p-Akt in H2O2-treated BRL-3A cells. These effects of DHEA were abolished when the cells were pretreated with the PI3K inhibitor LY294002. No changes were observed on the p-ERK1/2, p-p38, and p-JNK protein levels in H2O2-induced BRL-3A cells pretreated with DHEA. In conclusion, our data demonstrate that DHEA protects BRL-3A cells against H2O2-induced oxidative stress and apoptosis through mechanisms that do not involve its biotransformation into steroid hormones or the activation of sex hormone receptors. Importantly, the protective effect of DHEA on BRL-3A cells was mainly associated with PI3K/Akt signaling pathways, rather than MAPK signaling pathways.

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Punicalagin Prevents Hypoxic Pulmonary Hypertension via Anti-Oxidant Effects in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x16500439 ◽

2016 ◽

Vol 44 (04) ◽

pp. 785-801 ◽

Cited By ~ 13

Author(s):

Jingyun Shao ◽

Peng Wang ◽

An Liu ◽

Xusheng Du ◽

Jie Bai ◽

...

Keyword(s):

Oxidative Stress ◽

Pulmonary Hypertension ◽

Endothelial Dysfunction ◽

Pulmonary Arteries ◽

Pomegranate Juice ◽

No Production ◽

Protective Effects ◽

Hypoxic Pulmonary Hypertension ◽

Beneficial Effects ◽

Anti Oxidant

Punicalagin (PG), a major bioactive ingredient in pomegranate juice, has been proven to have anti-oxidative stress properties and to exert protective effects on acute lung injuries induced by lipopolysaccharides. This study aimed to investigate the effects of PG treatment on hypoxic pulmonary hypertension (HPH) and the underlying mechanisms responsible for the effects. Rats were exposed to 10% oxygen for 2 wk (8 h/day) to induce the HPH model. PG (5, 15, 45[Formula: see text]mg/kg) was orally administered 10[Formula: see text]min before hypoxia each day. PG treatments at the doses of 15 and 45[Formula: see text]mg/kg/d decreased the mean pulmonary arterial pressure (mPAP) and alleviated right ventricular hypertrophy and vascular remodeling in HPH rats. Meanwhile, PG treatment attenuated the hypoxia-induced endothelial dysfunction of pulmonary artery rings. The beneficial effects of PG treatment were associated with improved nitric oxide (NO)-cGMP signaling and reduced oxidative stress, as evidenced by decreased superoxide generation, gp91[Formula: see text] expression and nitrotyrosine content in the pulmonary arteries. Furthermore, tempol’s scavenging of oxidative stress also increased NO production and attenuated endothelial dysfunction and pulmonary hypertension in HPH rats. Combining tempol and PG did not exert additional beneficial effects compared to tempol alone. Our study indicated for the first time that PG treatment can protect against hypoxia-induced endothelial dysfunction and pulmonary hypertension in rats, which may be induced via its anti-oxidant actions.

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L-Carnosine Stimulation of Coenzyme Q10 Biosynthesis Promotes Improved Mitochondrial Function and Decreases Hepatic Steatosis in Diabetic Conditions

Antioxidants ◽

10.3390/antiox10050793 ◽

2021 ◽

Vol 10 (5) ◽

pp. 793

Author(s):

Cheng Schwank-Xu ◽

Elisabete Forsberg ◽

Magnus Bentinger ◽

Allan Zhao ◽

Ishrath Ansurudeen ◽

...

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Mouse Model ◽

Mitochondrial Function ◽

Diabetes Complications ◽

Synergistic Effects ◽

Coenzyme Q ◽

Protective Effects ◽

Beneficial Effects

Mitochondrial dysfunction in type 2 diabetes leads to oxidative stress, which drives disease progression and diabetes complications. L-carnosine, an endogenous dipeptide, improves metabolic control, wound healing and kidney function in animal models of type 2 diabetes. Coenzyme Q (CoQ), a component of the mitochondrial electron transport chain, possesses similar protective effects on diabetes complications. We aimed to study the effect of carnosine on CoQ, and assess any synergistic effects of carnosine and CoQ on improved mitochondrial function in a mouse model of type 2 diabetes. Carnosine enhanced CoQ gene expression and increased hepatic CoQ biosynthesis in db/db mice, a type 2 diabetes model. Co-administration of Carnosine and CoQ improved mitochondrial function, lowered ROS formation and reduced signs of oxidative stress. Our work suggests that carnosine exerts beneficial effects on hepatic CoQ synthesis and when combined with CoQ, improves mitochondrial function and cellular redox balance in the liver of diabetic mice. (4) Conclusions: L-carnosine has beneficial effects on oxidative stress both alone and in combination with CoQ on hepatic mitochondrial function in an obese type 2 diabetes mouse model.

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NAD+ treatment can increase directly the antioxidant capacity of rotenone-treated differentiated PC12 cells

10.1101/498162 ◽

2018 ◽

Author(s):

Jie Zhang ◽

Yunyi Hong ◽

Wei Cao ◽

Haibo Shi ◽

Weihai Ying

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Antioxidant Capacity ◽

Pc12 Cells ◽

Mitochondrial Permeability Transition ◽

Permeability Transition ◽

Protective Effects ◽

Beneficial Effects ◽

Differentiated Pc12 Cells ◽

Major Index

NAD+ administration can produce profound beneficial effects in the animal models of aging and a number of diseases. Since oxidative stress plays key pathological roles in aging and multiple major disorders, it is crucial to elucidate the mechanisms underlying the protective effects of NAD+ administration on oxidative stress-induced cell death. Previous studies have suggested that NAD+ treatment can decrease oxidative cell death indirectly by such mechanisms as preventing mitochondrial permeability transition, while it is unclear if NAD+ administration may decrease oxidative cell death by increasing directly the antioxidant capacity of the cells. Our current study used rotenone-treated differentiated PC12 cells as a cellular model to test our hypothesis that NAD+ treatment may increase directly the antioxidant capacity of the cells exposed to oxidative stress. Our study has indicated that NAD+ treatment can significantly attenuate the rotenone-induced increase in oxidative stress in the cells. Moreover, NAD+ treatment can significantly enhance the GSH/GSSG ratio, a major index of antioxidant capacity, of rotenone-treated cells. Collectively, our study has provided the first evidence indicating that NAD+ treatment can increase directly the antioxidant capacity of cells exposed to oxidative stress. These findings have suggested a novel mechanism underlying the profound protective effects of NAD+ administration in numerous disease models: NAD+ administration can decrease oxidative stress-induced cell death by enhancing directly the antioxidant capacity of the cells. Our finding has also highlighted the nutritional potential of NAD+.

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The Potential of Lisosan G as a Possible Treatment for Glaucoma

Frontiers in Pharmacology ◽

10.3389/fphar.2021.719951 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rosario Amato ◽

Maria Grazia Rossino ◽

Maurizio Cammalleri ◽

Anna Maria Timperio ◽

Giuseppina Fanelli ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Properties ◽

Nutritional Supplement ◽

Added Value ◽

Protective Effects ◽

Blood Retinal Barrier ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Temporal Profiles ◽

Retinal Pathologies

Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.

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Beneficial effects of Fenugreek seeds (Trigonella foenum graecum L) added in the diet of diabetic rats

JOURNAL OF ADVANCES IN CHEMISTRY ◽

10.24297/jac.v8i2.4037 ◽

2012 ◽

Vol 8 (2) ◽

pp. 1555-1565 ◽

Cited By ~ 1

Author(s):

Najla Hfaiedh ◽

Sabah Dhibi ◽

Sakria Mbarki ◽

Jean-Claude Murat ◽

Abdel Fattah Elfeki

Keyword(s):

Oxidative Stress ◽

Alkaline Phosphatase ◽

Thyroid Dysfunction ◽

Diabetic Rats ◽

Protective Effects ◽

Fenugreek Seeds ◽

Beneficial Effects ◽

Trigonella Foenum Graecum ◽

Trigonella Foenum Graecum L ◽

And Oxidative Stress

Protective effects of Fenugreek seeds (Trigonella foenum graecum L), added in the diet, upon oxidative stress and dysfunctions in kidney, thyroid and liver of alloxan-diabetic rats were investigated.In our study, the alloxan-induced diabetes triggered 1) increased levels of glucose, total cholesterol and triglycerides in blood, 2) increased activities of alkaline phosphatase and transaminases in blood, 3) increased levels of creatinine, urea and protein in blood, 4) a decreased level of TSH and an increased level of free thyroxin in plasma.In addition, an oxidative stress, evidenced by an increase of lipids peroxidation level and superoxide dismutase activity associated with a decrease of glutathione peroxidase and catalase activities in hepatic and renal tissues, was observed.When Fenugreek seeds powder (100g/kg) was added in the food for 30 days, all this parameters were significantly shifted to more normal values.In conclusion, fenugreek seeds powder displays beneficial effects upon hepatotoxicity, nephropathy, thyroid dysfunction and oxidative stress in alloxan-diabetic rats. This property could be attributed to the presence of antioxidant components, such as complex polysaccharides and phenolic acids, as confirmed by analyses.

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Acrylamide Induced Oxidative Cellular Senescence in Embryonic Fibroblast Cell Line (NIH 3T3): A Protection by Carvacrol

Jundishapur Journal of Natural Pharmaceutical Products ◽

10.5812/jjnpp.109399 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Mehdi Evazalipour ◽

Pouya Safarzadeh Kozani ◽

Pooria Safarzadeh Kozani ◽

Sahar Shabani ◽

Bahar Rezaei Soufi ◽

...

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Cell Line ◽

Cellular Senescence ◽

Fibroblast Cell ◽

Protective Effects ◽

Proliferating Cells ◽

Beneficial Effects ◽

Nih 3T3 ◽

Embryonic Fibroblast

Background: Stress-induced cellular senescence is a perpetual state of cell cycle arrest occurring in proliferating cells in response to stressful conditions. It is believed that oxidative stress plays a unique role in this process. As a reactive chemical compound that can induce oxidative stress, acrylamide is widely applied in several fields. Carvacrol is a liquid phenolic monoterpenoid found in essential oils of some plants and is known for its antioxidant and anticarcinogenic properties. Objectives: The current study aimed to evaluate the effects of carvacrol on oxidative stress and cellular senescence induced by acrylamide in the NIH 3T3 cell line. Methods: NIH 3T3 embryonic fibroblast cells were exposed to different concentrations of acrylamide, carvacrol, and H2O2 in a cell culture medium. The level of β-galactosidase (SA-β-gal) activity, as a marker of cellular senescence, was measured using staining and quantitative assays. Furthermore, to measure oxidative stress parameters, the content of glutathione and lipid peroxidation were determined. Results: Acrylamide could induce premature senescence evident by the elevated lipid peroxidation and SA-β-gal activity and declined cell viability and glutathione. Moreover, carvacrol showed beneficial effects on both acrylamide- and H2O2-induced cellular senescence by significantly reversing or subsiding the effect of oxidative stress and mediating its consequences. Conclusions: It can be concluded that carvacrol has protective effects against oxidative cellular senescence induced by acrylamide in the NIH 3T3 cell line.

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Beneficial Effects of Naringenin in Cigarette Smoke-Induced Damage to the Lung Based on Bioinformatic Prediction and In Vitro Analysis

Molecules ◽

10.3390/molecules25204704 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4704

Author(s):

Pan Chen ◽

Ziting Xiao ◽

Hao Wu ◽

Yonggang Wang ◽

Weiyang Fan ◽

...

Keyword(s):

Oxidative Stress ◽

Cigarette Smoke ◽

Bioinformatic Analysis ◽

Protective Effects ◽

Nrf2 Pathway ◽

Beneficial Effects ◽

Aryl Hydrocarbon ◽

Vitro Analysis ◽

Lung Health

Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.

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