Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats

Li, Qinghai; Wang, Jun; Zhu, Xianying; Zeng, Zhilin; Wu, Xiaomei; Xu, Yu; Xie, Jungang; Yu, Jun

doi:10.1016/j.biopha.2017.10.007

Cited by 32 publications

(24 citation statements)

References 52 publications

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“…In our study, CS was found to upregulate phospho-AKT (Ser 473), PCNA (proliferation marker), and MMP9 protein levels in HPASMCs, while RASEF overexpression inhibited these changes. Our previous study clarified the important role of MMP9 in PASMC migration in a monocrotaline-induced PH model [33], and some studies have reported AKT signaling could regulate MMP9 expression [50, 51]. The current result that CS upregulated MMP9 protein expression in HPASMCs is similar to that of Ghosh et al [52].…”

Section: Discussionsupporting

confidence: 82%

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Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling

Liu

et al. 2019

Respir Res

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Background Pulmonary hypertension (PH) is a progressive and fatal disease. While cigarette smoke can change DNA methylation status, the role of such molecular alterations in smoke-associated PH is unclear. Methods A PH rat model was developed by exposing animals to cigarette smoke for 3 months. Right ventricular systolic pressure was measured with a right heart catheter. Histological changes (right ventricular hypertrophy index, medial wall thickness in pulmonary arteries (PAs)) and DNMT1 protein levels in rat PAs or primary human PA smooth muscle cells (HPASMCs) exposed to cigarette smoke extract were assessed. Methylation sequencing and MassArray® were used to detect genomic and RASEF promoter methylation status, respectively. After DNMT1 knockdown and cigarette smoke extract exposure, HPASMCs behavior (proliferation, migration) and RASEF methylation status were examined; RASEF mRNA expression was evaluated by real-time-polymerase chain reaction. RASEF overexpression viral vectors were used to assess the impact of RASEF on rat PH and HPASMCs remodeling. Results Higher right ventricular systolic pressure, medial wall thickness, and right ventricular hypertrophy index values were observed in the smoking group rats. Smoke exposure increased DNMT1 expression and RASEF methylation levels in rat PAs and HPASMCs. Cigarette smoke extract induced HPASMCs behavioral changes and RASEF hypermethylation followed by silencing, while DNMT1 knockdown markedly inhibited these changes. RASEF overexpression distinctly inhibited PH and HPASMCs remodeling, possibly through phospho-AKT (Ser473), PCNA, and MMP9 downregulation. Conclusions Cigarette smoke caused PA remodeling in PH rats related to RASEF hypermethylation. These results expand our understanding of key epigenetic mechanisms in cigarette smoke-associated PH and potentially provide a novel therapeutic target for PH. Electronic supplementary material The online version of this article (10.1186/s12931-019-1014-1) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 82%

“…A 3F polyethylene catheter and the PowerLab system (AD Instruments, Australia) were used to test right ventricular (RV) systolic pressure (RVSP) in vivo as described previously [33]. After hemodynamic measurements were completed, rats were sacrificed as described above and hearts divided into the RV and left ventricle plus septum (LV + S).…”

Section: Methodsmentioning

confidence: 99%

Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling

Liu

et al. 2019

Respir Res

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“…Study in vitro also found that DMY (100 μM) pre-treatment for 12 h inhibited IL-6-induced human pulmonary arterial smooth muscle cells (HPASMCs) migration. Moreover, both phosphorylation of signal transducer and activator of transcription 3 (STAT3, as the vital downstream signal of IL-6) and matrix metalloproteinase-9 (MMP9, as a critical mediator for migration) were suppressed by DMY in MCT induced PAH of rats and IL-6 stimulated HPASMCs ( Li et al, 2017 ). DMY pre-treatment significantly attenuated hydrogen peroxide (H 2 O 2 )-induced apoptosis and inhibited intracellular ROS over-production in HUVECs.…”

Section: Cardiovascular Systemmentioning

confidence: 99%

Recent Update on the Pharmacological Effects and Mechanisms of Dihydromyricetin

et al. 2018

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As the most abundant natural flavonoid in rattan tea, dihydromyricetin (DMY) has shown a wide range of pharmacological effects. In addition to the general characteristics of flavonoids, DMY has the effects of cardioprotection, anti-diabetes, hepatoprotection, neuroprotection, anti-tumor, and dermatoprotection. DMY was also applied for the treatment of bacterial infection, osteoporosis, asthma, kidney injury, nephrotoxicity and so on. These effects to some extent enrich the understanding about the role of DMY in disease prevention and therapy. However, to date, we still have no outlined knowledge about the detailed mechanism of DMY, which might be related to anti-oxidation and anti-inflammation. And the detailed mechanisms may be associated with several different molecules involved in cellular apoptosis, oxidative stress, and inflammation, such as AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), protein kinase B (Akt), nuclear factor-κB (NF-κB), nuclear factor E2-related factor 2 (Nrf2), ATP-binding cassette transporter A1 (ABCA1), peroxisome proliferator-activated receptor-γ (PPARγ) and so on. Here, we summarized the current pharmacological developments of DMY as well as possible mechanisms, aiming to push the understanding about the protective role of DMY as well as its preclinical assessment of novel application.

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“…Dihydromyricetin (DMY), which is the main flavonoid of AG with a content of up to 35% [7], showed antiproliferation capacities in lung [8], breast, [9], and ovarian cancer [10], improvements on hypertension [11], hyperlipidemia [12,13] and abnormal blood sugar levels [14], as well as neuroprotective activity against Alzheimer's disease [15], Parkinson's disease [16], alcohol addiction, depression [17], and dermatoprotection [18]. In addition, a preventive effect on myocardial fibrosis [19], myocardial hypertrophy [20], and cardiac ischemia/reperfusion injury [21] was reported.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High‐Fat Diet Hamster

Fan

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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e flavonoid dihydromyricetin (DMY) is the main component of Ampelopsis grossedentata (Hand-Mazz) W. T. Wang (AG), a daily beverage and folk medicine used in Southern China to treat jaundice hepatitis, cold fever, and sore throat. Recently, DMY and AG were shown to have a beneficial effect on lipid metabolism disorder. However, the mechanisms of how DMY and AG protect the liver during lipid metabolism disorder remain unclear. In this study, we first analyzed the chemical compounds of AG by HPLC-DAD-ESI-IT-TOF-MS n . Of the 31 compounds detected, 29 were identified based on previous results. en, the effects of DMY and AG on high-fat diet hamster livers were studied and the metabolite levels and metabolic pathway activity of the liver were explored by 1 H NMR metabolomics. Compared to the high-fat diet group, supplementation of AG and DMY attenuated the high-fat-induced increase in body weight, liver lipid deposition, serum triglycerides and total cholesterol levels, and normalized endogenous metabolite concentrations. PCA and PLS-DA score plots demonstrated that while the metabolic profiles of hamsters fed a high-fat diet supplemented with DMY or AG were both far from those of hamsters fed a normal diet or a high-fat diet alone, they were similar to each other. Our data suggest that the underlying mechanism of the protective effect of DMY and AG might be related to an attenuation of the deleterious effect of high-fat diet-induced hyperlipidemia on multiple metabolic pathways including amino acid metabolism, ketone body metabolism, energy metabolism, tricarboxylic acid cycle, and enhanced fatty acid oxidation.

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Dihydromyricetin prevents monocrotaline-induced pulmonary arterial hypertension in rats

Cited by 32 publications

References 52 publications

Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling

Role of RASEF hypermethylation in cigarette smoke-induced pulmonary arterial smooth muscle remodeling

Recent Update on the Pharmacological Effects and Mechanisms of Dihydromyricetin

Metabolomics of the Protective Effect of Ampelopsis grossedentata and Its Major Active Compound Dihydromyricetin on the Liver of High‐Fat Diet Hamster

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