Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways

Qin, Meng; Luo, Yun; Meng, Xiangbao; Wang, Min; Wang, Hongwei; Song, Shiyu; Ye, Jingxue; Pan, Rui‐Le; Yao, Fan; Wu, Po-Liang; Sun, Guibo; Sun, Xiaobo

doi:10.1016/j.vph.2015.03.002

Cited by 82 publications

(77 citation statements)

References 44 publications

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“…Additionally, the ERK signaling pathway is reported to be involved in DCM, wherein ERK is significantly phosphorylated and inhibits Nrf2 signaling, resulting in cell hypertrophy1240. Furthermore, our previous studies have confirmed that phosphorylation of Akt regulates Nrf2 activation and HO-1 expression1641. However, the impacts of Myr on Akt and ERK signaling in the diabetic heart were unclear.…”

Section: Discussionmentioning

confidence: 97%

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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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Section: Discussionmentioning

confidence: 97%

“…The control and model groups received the aseptic 0.5% CMC-Na treatment every day (i.g.). Doses of myricitrin and metformin used were based on the previous studies 4149.…”

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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“…It is highly limited to search for the related literature on myricitrin, as a PKC inhibitor to fight against apoptosis. Furthermore, our colleagues have found that myricitrin obviously promotes PI3K/Akt signaling pathway [17], which provides the solid foundation for our subsequent studies. To confirm whether myricitrin exerted its anti-apoptotic roles by Akt or other pathways, an Akt inhibitor (LY294002) was employed in this research.…”

Section: Discussionmentioning

confidence: 83%

“…Our laboratory previously demonstrated that myricitrin can attenuate endothelial cell apoptosis via PI3K/Akt signaling activation [17]. In addition, myricitrin reportedly possesses effective antioxidant, anti-inflammatory and antifibrotic activity [18].…”

Section: Introductionmentioning

confidence: 99%

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

et al. 2016

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Hyperglycemia, as well as diabetes mellitus, has been shown to trigger cardiac cell apoptosis. We have previously demonstrated that myricitrin prevents endothelial cell apoptosis. However, whether myricitrin can attenuate H9c2 cell apoptosis remains unknown. In this study, we established an experiment model in H9c2 cells exposed to high glucose. We tested the hypothesis that myricitrin may inhibit high glucose (HG)-induced cardiac cell apoptosis as determined by TUNEL staining. Furthermore, myricitrin promoted antioxidative enzyme production, suppressed high glucose-induced reactive oxygen species (ROS) production and decreased mitochondrial membrane potential (MMP) in H9c2 cells. This agent significantly inhibited apoptotic protein expression, activated Akt and facilitated the transcription of NF-E2-related factor 2 (Nrf2)-mediated protein (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1) expression as determined by Western blotting. Significantly, an Akt inhibitor (LY294002) or HO-1 inhibitor (ZnPP) not only inhibited myricitrin-induced HO-1/NQO-1 upregulation but also alleviated its anti-apoptotic effects. In summary, these observations demonstrate that myricitrin activates Nrf2-mediated anti-oxidant signaling and attenuates H9c2 cell apoptosis induced by high glucose via activation of Akt signaling.

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“…At present, the exact pathological mechanism underlying SANFH is not fully known; however, numerous studies have indicated that a reduced number and the weakened activity of MSCs in the femoral neck and proximal femur may be among the underlying causes of SANFH (22)(23)(24). Due to the reduction in the number or the activity level of MSCs, their osteogenetic capacity decreases, and the lesion of necrotic bone cannot be effectively repaired, leading to the collapse of the femoral head (25).…”

Section: Discussionmentioning

confidence: 99%

Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head

Wang

Teng

Zhang

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Steroids are known to inhibit osteogenic differentiation and decrease bone formation in mesenchymal stem cells (MSCs), while concomitantly inducing steroid-induced avascular necrosis of the femoral head (SANFH). The aim of the present study was to evaluate the function of MSCs on differentiation in SANFH and investigate the pathobiological mechanisms underlying SANFH in a rabbit model. MSCs in the control, trauma-induced ANFH (TANFH) and SANFH groups were incubated with low-glucose complete Dulbecco's modified Eagle's medium containing 10% fetal bovine serum. A number of adipocytes in the MSCs were stained with Sudan III and counted using a light microscope. The mRNA and protein expression levels of the adipose-specific 422 (AP2), peroxisome proliferator-activated receptor-γ (PPARγ), RUNX2, collagen type I (Col I) and miR-103 in the MSCs were determined using quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the activities of osteocalcin (OC), alkaline phosphatase (ALP) and triglyceride (TG) in MSCs were analyzed using radioimmunoassay and determination kits. In the MSCs of the SANFH group, the mRNA and protein expression levels of AP2 and PPARγ were increased, while those of RUNX2 and Col I were reduced. Furthermore, the levels of OC and ALP activity in the MSCs of the SANFH group were decreased, and the activity of TG in the MSCs of the SANFH group was increased. In addition, the expression of miR-103 in the MSCs of the SANFH group was elevated. Following routine culture of the MSCs for 3 weeks, the number of adipocytes among the MSC population of the SANFH group was increased. Therefore, the results of the present study suggest that the osteogenic differentiation of MSCs in the SANFH was mitigated, while fat differentiation was promoted, which provides a novel explanation for the pathological changes associated with SANFH.

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Myricitrin attenuates endothelial cell apoptosis to prevent atherosclerosis: An insight into PI3K/Akt activation and STAT3 signaling pathways

Cited by 82 publications

References 44 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

Myricitrin Attenuates High Glucose-Induced Apoptosis through Activating Akt-Nrf2 Signaling in H9c2 Cardiomyocytes

Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head

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