Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Su, Zhilei; Sun, Hanqi; Zhao, Wei; Chen, Xue; Hang, Pengzhou; Zhu, Wenliang; Du, Zhenhong

doi:10.1159/000484120

Cited by 18 publications

(16 citation statements)

References 42 publications

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“…In the present research, single-cell recordings showed that APD 20 , APD 50 , and APD 90 were markedly prolonged in WT-HFD mice compared with WT-ND mice. Our result is in agreement with a previous work by Bai and coworkers in myocytes isolated from HFD-fed rat hearts [18]. In their experiments, APD 90 was markedly elongated by HFD.…”

Section: Discussionsupporting

confidence: 94%

The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice

Shuai

Kong

et al. 2020

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Myeloid differentiation protein 1 (MD1) is exerted an anti-arrhythmic effect in obese mice. Therefore, we sought to clarify whether MD1 can alter the electrophysiological remodeling of cardiac myocytes from obese mice by regulating voltage-gated potassium current and calcium current. MD1 knockout (KO) and wild type (WT) mice were given a high-fat diet (HFD) for 20 weeks, starting at the age of 6 weeks. The potential electrophysiological mechanisms were estimated by whole-cell patch-clamp and molecular analysis. After 20-week HFD feeding, action potential duration (APD) from left ventricular myocytes of MD1-KO mice revealed APD 20 , APD 50 , and APD 90 were profoundly enlarged. Furthermore, HFD mice showed a decrease in the fast transient outward potassium currents (I to,f), slowly inactivating potassium current (I K, slow), and inward rectifier potassium current (I K1). Besides, HFD-fed mice showed that the current density of I CaL was significantly lower, and the haft inactivation voltage was markedly shifted right. These HFD induced above adverse effects were further exacerbated in KO mice. The mRNA expression of potassium ion channels (Kv4.2, Kv4.3, Kv2.1, Kv1.5, and Kir2.1) and calcium ion channel (Cav1.2) was markedly decreased in MD1-KO HFD-fed mice. MD1 deletion led to down-regulated potassium currents and slowed inactivation of L-type calcium channel in an obese mice model.

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Section: Discussionsupporting

confidence: 94%

The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice

Shuai

Kong

et al. 2020

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“…Compared with those in the ND group, the LDL, TG and TC circulatory levels were significantly higher in the HFD group (Supplementary Figure 1). Interestingly, 6-week treatment of AE reversed the hyperlipidemia and AE reduced LDL, TG, and TC circulatory levels induced by HFD, consistent with our previous study [17]. Increased inflammatory infiltration is one of the hallmarks of the progression of inflammation; hematoxylin-eosin staining validated our guess.…”

Section: Ae Reduces Myocardial Inflammatory Injury In Hfdsupporting

confidence: 91%

“…As a member of the anthraquinone family, AE occurs in the leaves of aloe and exhibits a variety of pharmacological properties, such as antibacterial, anticancer, and antioxidant activities. Recently, AE has been reported to have antiinflammatory effects [16]; in addition, AE previously showed a lipid-lowering effect in vivo [17]. However, the effect of AE on hyperlipidemia-induced cardiac inflammation has not been reported.…”

Section: Introductionmentioning

confidence: 99%

Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway

Chen

Feng

Yuan

et al. 2020

Mediators of Inflammation

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Background. Aloe emodin (AE) is a lipid-lowering agent, which could be used to treat hyperlipidemia, thereby reducing the risk of cardiovascular disease. Recent evidence suggests that hyperlipidemia is associated with many cardiac pathological alterations and might worsen myocardial damages. Purpose. The purpose of this study is to evaluate the potential roles and mechanisms of AE in hyperlipidemia-induced oxidative stress and inflammation in the heart. Study Design. We established a hyperlipidemia-induced cardiac inflammation model in rats and cells then administered AE and observed its effect on hyperlipidemia-induced cardiac inflammation. Methods. We used a mouse model of hyperlipidemia caused by a high-fat diet (HFD) for 10 weeks and cell culture experimental models of inflammation in the heart stimulated by PA for 14 h. Inflammatory markers were detected by qRT-PCR, WB, and immunofluorescence. Results. We demonstrated that the expression levels of proinflammatory cytokines IL-1β, IL-6, and TNF-α were increased in the HFD group compared to the normal diet (ND) group, whereas AE treatment significantly reduced their levels in the myocardium. In addition, vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM-1) protein expressions were also inhibited by AE. Our in vitro study showed AE treatment dose-dependently decreased the expression of IL-1β, IL-6, and TNF-α in PA-treated H9C2 cells. Further experiments revealed that AE inhibited PA-induced cell death and promoted the production of intracellular reactive oxygen species (ROS). Mechanically, AE significantly suppressed the upregulation in protein levels of TLR4, IκB, and p-P65l in vivo and in vitro. Conclusion. Taken together, our findings disclose that AE could alleviate HFD/PA-induced cardiac inflammation via inhibition of the TLR4/NF-κB signaling pathway. Thus, AE may be a promising therapeutic strategy for preventing hyperlipidemia-induced myocardial injury.

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“…33 Previous studies have indicated that Rhubarb has a promising protective effect against lung and renal fibrosis. 34,35 AE is an active compound in the plant rhubarb, 36 which is a traditional medicine used widely in the treatment of a variety of diseases in China. 37 Our study showed for the first time that AE protected against renal injury in a UUO model.…”

Section: Discussionmentioning

confidence: 99%

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

Dou

Liu

et al. 2019

Rejuvenation Research

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Fibrosis is the major pathological feature of chronic kidney disease (CKD). Aloe-emodin (AE), one of the main active compounds in Rhubarb, is widely used for renal protection. However, mechanisms implied in the modulation of kidney fibrosis after AE treatment for CKD remain elusive. Here, we explored the protective effects of AE for renal fibrosis and the involved mechanisms in vivo and in vitro. The renal fibrosis mice model was established by unilateral ureteral obstruction (UUO). We found that AE administration significantly ameliorated UUO-induced impairment of kidney, evidenced by improved histopathological abnormalities, body weight, and abnormal renal function in mice model. Immunohistochemical staining showed that TGF-β1 and Fibronectin expressions were significantly decreased in UUO mice compared with sham group. Meanwhile, we found that AE suppressed the activation of the PI3K/Akt/mTOR pathway induced by TGF-β1 in vivo. AE improved cell survival and decreased the level of fibrosis-related proteins under TGF-β1-induced fibrosis in HK-2 cells as well as in vitro. Furthermore, both wortmannin, an inhibitor of PI3K, and short-hairpin RNAs of PI3K knockdown abrogated TGF-β1-induced phosphorylation of Akt and mTOR, and decreased the suppression of fibrosis. These findings indicated that AE alleviated fibrosis by inhibiting PI3K/Akt/mTOR pathway in vivo and in vitro, which may provide a potential therapeutic option for CKD.

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Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Cited by 18 publications

References 42 publications

The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice

The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice

Aloe Emodin Reduces Cardiac Inflammation Induced by a High-Fat Diet through the TLR4 Signaling Pathway

Aloe-Emodin Ameliorates Renal Fibrosis Via Inhibiting PI3K/Akt/mTOR Signaling PathwayIn VivoandIn Vitro

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