Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation

Rani, Neha; Bharti, Sudhakar; Bhatia, Jagriti; Nag, Tapas Chandra; Ray, Ruma; Arya, Dharamvir Singh

doi:10.1016/j.cbi.2016.03.015

Cited by 100 publications

(67 citation statements)

References 37 publications

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“…The above two can be concurrently induced by excess AGEs19. Intracellular ROS levels were assessed by measuring mitochondrial superoxide using MitoSOX Red.…”

Section: Resultsmentioning

confidence: 99%

“…JC-1 (Invitrogen, Waltham, MA, USA) was used to determine the changes in mitochondrial transmembrane potential as previous reported19. Briefly, after treatment, H9c2 cardiomyocytes were incubated with JC-1 (5 μmol/L) in the dark at 37 °C for 30 min and were then washed with PBS followed by fluorescence microscopy (DM4000B, Leica, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Zhang

Shen

Chen

et al. 2017

Sci Rep

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Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.

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“…The above two can be concurrently induced by excess AGEs19. Intracellular ROS levels were assessed by measuring mitochondrial superoxide using MitoSOX Red.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Zhang

Shen

Chen

et al. 2017

Sci Rep

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“…This study did not examine the inhibitory effects of chysin on retinal inflammation. Nevertheless, the anti-inflammatory and antioxidant effects of chrysin would be of potential benefits in pathologies of retinal vascular activation of DR [29,43]. The presence of advanced glycation end products (AGE) in the retinal blood vessel walls contributes towards vascular occlusion and increased permeability of retinal endothelial cells causing vascular leakage [4,44].…”

Section: Discussionmentioning

confidence: 99%

Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

et al. 2016

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Diabetic retinopathy (DR) develops in a significant proportion of patients with chronic diabetes, characterized by retinal macular edema and abnormal retinal vessel outgrowth leading to vision loss. Chrysin, a naturally-occurring flavonoid found in herb and honeycomb, has anti-inflammatory, antioxidant, and anti-cancer properties. This study sought to determine the protective effects of chrysin on retinal neovascularization with abnormal vessels and blood-retinal barrier (BRB) breakdown in 33 mM glucose-exposed human retinal endothelial cells and in db/db mouse eyes. High glucose caused retinal endothelial apoptotic injury, which was inhibited by submicromolar chrysin. This compound diminished the enhanced induction of HIF-1α, vascular endothelial growth factor (VEGF), and VEGF receptor-2 (VEGFR2) in high glucose-exposed retinal endothelial cells. Consistently, oral administration of 10 mg/kg chrysin reduced the induction of these proteins in db/db mouse eye tissues. In addition, chrysin restored the decrement of VE-cadherin and ZO-1 junction proteins and PECAM-1 in hyperglycemia-stimulated retinal endothelial cells and diabetic mouse retina, possibly maintaining tight cell-cell interactions of endothelial cells and pericytes. Anti-apoptotic chrysin reduced the up-regulation of Ang-1, Ang-2, and Tie-2 crucial to retinal capillary occlusion and BRB permeability. Furthermore, orally treating chrysin inhibited acellular capillary formation, neovascularization, and vascular leakage observed in diabetic retinas. These observations demonstrate, for the first time, that chrysin had a capability to encumber diabetes-associated retinal neovascularization with microvascular abnormalities and BRB breakdown.

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“…Subsequently, the sections were washed and incubated for 30 min with peroxidase-conjugated streptavidin-biotin complex. The target proteins (Bax/Bcl-2) were visualized after incubation in peroxidase substrate using 3,3′-diaminobenzidine as the chromogen and the sections were counterstained with haematoxylin and analyzed using light microscopy (Motic AE2000 inverted microscope, Motic microscope, Kowloon Bay, Kowloon, Hong Kong, China) [37]. …”

Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as described previously [37]. Briefly, the myocardial tissues were separated by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS–PAGE) and transferred to nitrocellulose membrane that was blocked for 2 h with 5% bovine serum albumin.…”

Section: Methodsmentioning

confidence: 99%

The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway

Mahajan

Chandrayan

Patil

et al. 2017

IJMS

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We substantiated the role of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in the protective effect of apigenin against the myocardial infarction (MI) in diabetic rats. Diabetes was induced by intraperitoneal administration of a single dose of streptozotocin (55 mg/kg). The study groups included diabetic rats receiving vehicle, apigenin (75 mg/kg/day, orally), GW9662 (1 mg/kg/day, intraperitoneally), and a combination of apigenin and GW9662 for 14 days. The MI was induced in all the study groups except the diabetic control group by subcutaneous injection of 100 mg/kg/day of isoproterenol on the two terminal days. The diabetes and isoproterenol-induced MI was evident as a reduction in the maximal positive and negative rate of developed left ventricular pressure and an increase in the left ventricular end-diastolic pressure. The activities of creatine kinase on myocardial bundle (CK-MB) and lactate dehydrogenase (LDH) were also reduced. Apigenin treatment prevented the hemodynamic perturbations, restored the left ventricular function and reinstated a balanced redox status. It protected rats against an MI by attenuating myonecrosis, edema, cell death, and oxidative stress. GW9662, a PPAR-γ antagonist reversed the myocardial protection conferred by apigenin. Further, an increase in the PPAR-γ expression in the myocardium of the rats receiving apigenin reinforces the role of PPAR-γ pathway activation in the cardioprotective effects of apigenin.

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Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation

Cited by 100 publications

References 37 publications

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

Dietary Compound Chrysin Inhibits Retinal Neovascularization with Abnormal Capillaries in db/db Mice

The Protective Effect of Apigenin on Myocardial Injury in Diabetic Rats mediating Activation of the PPAR-γ Pathway

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