Marine Drugs
·
2021
·Vol. 19
·期 9
·485
·
IF 5.118
Ying Yan,Zhoumin Niu,Boyang Wang,Shangge Zhao,Chao Sun,Yuting Wu,Yuying Li,Hao Ying,Hongbing Liu
Dysregulation of cholesterol homeostasis is a major risk factor of atherosclerosis, which can lead to serious health problems, including heart attack and stroke. Liver X receptor (LXR) α and β are transcription factors belonging to the nuclear receptor superfamily, which play important roles in cholesterol homeostasis. Selectively activating LXRβ provides a promising strategy for the treatment of atherosclerosis. Here, we employed atherosclerotic apoE-knockout mice to evaluate the effects of saringosterol, a phytosterol with potent and selective action for LXRβ, which we identified previously in edible marine seaweedSargassum fusiforme. We found that saringosterol treatment reduced the atherosclerotic plaque burden without having undesirable adverse hepatic effects in apoE-deficient mice fed an atherogenic diet. Meanwhile, reduced serum levels of cholesterol, accompanied by altered expression of LXR-regulated genes involved in cholesterol absorption, transport, efflux, excretion, and elimination, were observed in apoE-knockout mice after saringosterol treatment. Together, our study not only establishes saringosterol as an effective cholesterol-lowering and anti-atherogenic phytosterol but also provides insights into the underlying mechanism.Keywords:saringosterol;liver X receptor;cholesterol metabolism;atherosclerosis;Sargassum fusiforme
研究领域:
药理学
·
心血管疾病
·
海洋生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 9
·1183
·
IF 8.2
Junying Jiao,Ning Xu,Zhixuan Hong,Lei Chang,Derong Huang,Yang Yu,Zhendi Wang,Yibai Li,Jiaxin Yu,Juntao Guo,You Wang,Lirun Kuang,Yong Wang,Bei Yang,Rui Zhao,Yongyong Hou,Huihui Wang,Qiang Zhang,Ping Xu,Yuanyuan Xu,Jingbo Pi,Jingqi Fu
Hypercholesterolemia and hyperlipidemia are major contributors to the pathogenesis and progression of atherosclerosis and cardiovascular diseases (CVDs). Nuclear factor erythroid-derived 2-like 2 (NRF2) exerts antioxidant and anti-inflammatory effects while regulating glucose and lipid metabolism. However, the precise role and molecular mechanisms of NRF2 in hepatic cholesterol metabolism remain incompletely understood. Approach and Results: ApoE -knockout ( ApoE -KO) mice were crossed with hepatocyte-specific Nrf2 -knockout ( Nrf2 (H)-KO) mice to explore how NRF2 modulated cholesterol metabolism and the progression of atherosclerosis in vivo. Atherosclerotic lesion areas in Nrf2 (H)-KO; ApoE -KO mice were significantly reduced compared with control counterparts ( Nrf2 -LoxP; ApoE -KO). Total cholesterol and LDL-cholesterol levels in plasma of Nrf2 (H)-KO; ApoE -KO mice were significantly decreased, consistent with atherosclerotic phenotypes. Furthermore, hepatic triglyceride levels and cholesterol contents were increased in Nrf2 (H)-KO; ApoE -KO mice. The hepatic transcriptomic analysis highlighted lipid metabolism pathway alterations in Nrf2 (H)-KO; ApoE -KO mice, and carboxylesterase 1 ( Ces1s ) and lipocalin gene family member major urinary proteins ( Mups ) clusters markedly reduced expression in Nrf2 (H)-KO; ApoE -KO livers. Liver proteomics analysis corroborated the transcriptomic findings. The current findings suggest that NRF2-modulated CES1s and MUPs may regulate cholesterol metabolism in the ApoE -KO model. Conclusions: Hepatocyte-specific Nrf2 deficiency significantly reduced plasma cholesterol levels, thereby attenuating atherosclerotic plaque formation and progression in the ApoE -KO background. This study established NRF2 in hepatocytes as a potential therapeutic target for controlling hypercholesterolemia and preventing atherosclerosis development.
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES
·
2020
·Vol. 129
·期 05
·339-348
·
IF 2.058
Mao Ouyang,Tao Qin,Hengdao Liu,Junya Lu,Caixia Peng,Qin Guo
Objective High-fat diet (HFD) increases the risk of inflammatory reaction and acute arterial thrombosis. Celastrol has been confirmed to regulate inflammatory cytokine levels in atherosclerotic animal models. However, the anti-thrombotic effects of celastrol have remained to be fully demonstrated. The present study was performed to investigate the beneficial effect of celastrol in HFD-induced inflammatory reaction and thrombosis in apolipoprotein (apo)E-/- mice. Materials and Methods Thrombogenic mice model was established using HFD-fed apoE-/- mice. The levels of mRNA and protein were assayed by RT-qPCR and western blotting, respectively. Immunohistochemistry (IHC) staining was performed to measure the protein expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the aortic endothelium of HFD-fed apoE-/- mice. Results The results demonstrated that the effect of HFD on inflammatory cytokines in mice with apoE-/- background was reversed by celastrol administration, and celastrol treatment inhibited the NOD-like receptor family, pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1β signaling cascades in peripheral blood mononuclear cells from HFD-fed apoE-/- mice. In addition, HFD enhanced adenosine diphosphate-induced platelet aggregation in normal C57BL/6 and apoE-/- mice, while celastrol administration reversed this. Furthermore, celastrol inhibited the pro-thrombotic effects of HFD in apoE-/- mice, and the underlying mechanism was mediated, at least partially, through the suppression of matrix metalloproteinase-2 and -9 expression. Conclusions Celastrol administration significantly attenuated HFD-induced inflammatory reaction, platelet aggregation and thrombosis in apoE-/- mice, and celastrol may be used as a drug for the prevention of HFD-induced inflammatory reaction and thrombus.
研究领域:
心血管疾病
·
药理学
·
炎症
·
血栓形成
✓ 已验证
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Youming Shi,Wenjiao Gu,Yujie Wei,Shuangyi Li,Shining Zhang,Ying jiang,Chuanjian Chen,Ting Liu,Limei Shuai,Xiaochun Zhou,Futian Tang
Purpose Atherosclerosis (AS) and atherosclerotic calcification (AC) are closely related to the cardiovascular diseases, largely due to its induction of vasomotor dysfunction. We previously reported that Calpain-1 inhibitor attenuated AS and AC. The present study was designed to investigate the effects and potential mechanisms of Calpain-1 knockout (Calpain-1 KO) in Apolipoprotein E KO (ApoE KO) mice on AS, AC, aortic vasomotor function as well as the liver dysfunction. Methods We hybridized ApoE KO mice with Calpain-1 KO mice to obtain ApoE /Calpain-1 double KO (A×C DKO) mice. The formation of AS and AC was evaluated and liver function was determined. Aortic vasomotor function was assessed. Contents of TNF-α, IL-6, IL-18, IL-1β and NO and the activity of AST, ALT, ALP and eNOS in serum were quantified. The mRNA expression of CD68, SR-A, CD36, PPAR-γ, LXR-α, ABCA1, BMP-2, OPN, ALP and Runx2 in aorta and/or liver were measured. Results The results showed that in comparison to C57 mice, ApoE KO mice demonstrated the significant increases in the areas of AS and AC, the increases in the mRNA expression of CD68 in the aorta, the increases in the AST, ALT and ALP activity in serum. ApoE KO mice also showed the dysfunction of the aortic contraction induced by phenylephrine and of the relaxation induced by acetylcholine. However, compared with ApoE KO mice, A×C DKO mice exhibited the significant attenuation of AS and AC and the downregulation of mRNA expression of CD68 in aorta. A×C DKO mice revealed the reduction of AST, ALT and ALP activity in serum, the improvements in aortic contraction and relaxation as well as the increases in eNOS activity and NO content in serum. A×C DKO mice also showed the decreases in the contents of TNF-α, IL-6, IL-18 and IL-1β in serum. The mRNA expression of CD68 in aorta, SR-A and CD36 in both aorta and liver of A×C DKO mice was downregulated, while that of PPAR-γ, LXR-α, and ABCA1 was upregulated in comparison of ApoE KO mice. In addition, the mRNA expression of BMP-2, OPN, ALP and Runx2 in aorta of A×C DKO mice was downregulated in comparison of ApoE KO mice. Conclusion The results suggested that deficiency of Calpain-1 attenuated the formation of AS and AC and improved vasomotor and liver dysfunction in ApoE KO mice through anti-inflammation, and modulation of the mRNA expression of genes related to AS and AC.
研究领域:
心血管疾病研究
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·
IF 7
Huiting Hu,Han-Feng Cui,Xia Yin,Qiqi Fan,Hai Shuai,Jing Zhang,Sheng Fu Liao,Wei Xiong,Dong he Jiang,Hao Fan,Wenming Liu,Guobing Wei
A dual-mode fluorescence and electrochemiluminescence (FL-ECL) sensor for apoE gene detection has been designed, harnessing the distinct properties of Ruthenium Metal Organic Framework Nanosheets (RuMOFNSs). The strategy capitalizes on the quenching effect of the Ru(bpy)₃²⁺ ECL signal by ferrocene, facilitating the creation of a multi-electron electrical signal marker known as bisferrocene. Through anchoring the P-DNA onto RuMOFNSs, bisferrocene effectively quenches both FL and ECL emissions. Introduction of the T-DNA, and the subsequent formation of double-stranded DNA, allows the ExoⅢ enzyme to remove the bisferrocene fragment, rejuvenating the signals. Impressively, the sensor boasts expansive detection linear ranges (1 fM to 1 nM for FL; 0.01 fM to 10 pM for ECL) and exceptional sensitivity (0.048 fM for FL; 0.016 fM for ECL). Its dual-mode framework grants heightened reliability via a self-validation mechanism, mitigating the occurrence of false positives. When juxtaposed with single-mode sensors, this dual-format exhibits marked superiority. Field tests further validate the sensor's efficacy in genuine sample analysis, highlighting its potential in precursory disease detection. This avant-garde methodology paves the way for advanced multi-signal responsive sensors, with profound implications for the future of diagnostic instruments.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Shao-Jun Zheng,Xiao-Yan Gao,Xiao-Han Diao,Nai-Dong Chen
Background Cardiovascular diseases, particularly atherosclerosis (AS), remain leading causes of mortality, with limited effective treatments available. Dendrobium huoshanense , a traditional medicinal herb, has shown promising anti-inflammatory and antioxidant effects, but its cardiovascular protective potential remains underexplored. Purpose This study aimed to explore the protective effects of Dendrobium huoshanense polysaccharides (DHP) against AS and elucidate the underlying mechanisms involved. Methods An ApoE(−/−) mice model of AS was established, and DHP was administered at different concentrations via gavage. After 14 weeks, serum and fecal samples were collected. The effects of DHP on lipid profiles, aortic plaques, matrix metalloproteinases (MMP-2 and MMP-9), and the Nrf2/HO-1 pathway were assessed. Additionally, metagenomic sequencing of fecal samples and untargeted metabolomics of serum were conducted and correlations between these findings were explored. Results DHP improved lipid profiles, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and enhanced superoxide dismutase (SOD) activity. It stabilized aortic plaques, suppressed MMP-2 and MMP-9 overexpression, and activated the Nrf2/HO-1 pathway. DHP also promoted gut microbiota balance, increasing Mucispirillum, Bifidobacterium , and Faecalibaculum while decreasing Desulfovibrionaceae and Eubacterium . Metabolomics revealed alterations in metabolites, including taurochenodeoxycholic acid and ursocolic acid, influencing amino acid, glycerophospholipid, and bile acid metabolism. Conclusions DHP effectively lowers lipid levels, stabilizes aortic plaques, restores gut microbiota balance, and corrects metabolic disturbances, thereby inhibiting the progression of atherosclerosis. These findings provide a scientific basis for the clinical use of DHP in AS prevention and treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 10
·5103-5114
·
IF 3.289
Zongyuan Wu,Zumeng Xia,Bangfu Wu,Fang Wei,Xin Lv,Ya Xie,Shuling Xu,Jiqu Xu,Hong Chen,Fenghong Huang
Atherosclerosis is a chronic disease associated with oxidative stress and inflammatory activation and is the main underlying trigger for cardiovascular disease. There are many cardiovascular health products in the market; in order to evaluate the effect of these products, in this paper, a novel lipid profiling platform was established using the shot-gun mass spectrum method for the analysis of free fatty acid and phospholipids, and the high performance liquid chromatography coupled with mass spectroscopy method for the analysis of lipid mediators and triacylglycerol, respectively, in serum from male apolipoprotein E-knock out mice after different diet interventions. Changes in the four lipids above, and pathways and regulation of lipid metabolism in mice from different groups were further investigated. The result showed that all cardiovascular health products showed some certain potential to alleviate atherogenesis and ameliorate inflammation; among them, lemon apple cider vinegar drink and seal oil could significantly decrease triacylglycerol in mouse serum. The establishment of this lipidome profiling platform helps to better understand the metabolism regulation and intervention mechanism of different cardiovascular health products in chronic diseases, such as atherogenesis. This platform could be applied to other cardiovascular health products and provide reliable lipid profiling data for their potential effect.
研究领域:
生物化学
·
代谢组学
·
心血管病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
·
2019
·
IF 3.277
Yan Jiang,Hongjiao Du,Xue Liu,Xi Fu,Xiaodong Li,Qian Cao
There is increasing evidence that atherosclerosis is the significant risk factor for cardiovascular diseases, which are the leading causes of morbidity and mortality worldwide. Artemisinin is a natural endoperoxides quiterpene lactone compound in Artemisia annua L with vasculoprotective effects. The primary aim of this study was to investigate whether artemisinin could be conferred an anti-atherosclerotic effect in high-fat diet (HFD)-fed ApoE–/– mice and explore the possible mechanism. We found that treatment with artemisinin (50 and 100 mg/kg) effectively ameliorated atherosclerotic lesions, such as foam cell formation, hyperplasia and fibrosis in the aortic intima. Atherosclerotic mice treated with artemisinin showed reduced inflammation by up-regulating adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) activation and by down-regulating nuclear factor-κB (NF-κB) phosphorylation and nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome expression in the aortas. In addition, artemisinin was found to promote AMPK activity in macrophages and its anti-inflammatory effect was neutralised by AMPK silence using specific siRNA. In conclusion, we demonstrate that artemisinin may protect the aortas from atherosclerotic lesions by suppression of inflammatory reaction via AMPK/NF-κB/NLRP3 inflammasomes signalling in macrophages.
研究领域:
心血管疾病
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
STRUCTURE
·
2025
·
IF 4.3
Shu-Cheng Fang,Liang Wang,Meng-Ting Cheng,Da Xu,Zhi-Peng Chen,Jie Wang,Wenli Liao,Yanyan Li,Cong-Zhao Zhou,Wen-Tao Hou,Yuxing Chen
The human ATP-binding cassette (ABC) transporter ABCA7 participates in the lipidation of apolipoprotein ApoE, a commonly recognized risk factor for Alzheimer’s disease (AD). How ABCA7 is involved in the molecular pathogenesis of AD remains poorly understood. Using cryoelectron microscopy (cryo-EM), we determined ABCA7 structures in the apo and substrate-bound forms, respectively. Combined with activity assays, we assigned the residues that specifically bind two molecules of phosphatidylserine (PS) that are arranged in a “tail-to-tail” manner. Pull-down assays confirmed that ApoE directly interacts with ABCA7; and moreover, both ATPase and lipid transport activities of ABCA7 were significantly enhanced in the presence of ApoE. We also measured the activities of a familial AD variant and a protective clinically reported variant in the ABCA7 gene. Our findings not only give structural insights into ABCA7-mediated PS translocation, but we also provide first biochemical evidence for its link to AD by forwarding lipids to ApoE.
研究领域:
结构生物学
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2022
·
IF 5.895
Shuhua Shan,Ruopeng Yin,Jiangying Shi,Lizhen Zhang,Fengming Liu,Qinqin Qiao,Zhuoyu Li
Foxtail millet proteins and their hydrolysates have the potential to prevent atherosclerosis (AS). In our present study, a novel Bowman-Birk type major trypsin inhibitor from foxtail millet bran (FMB-BBTI) with an anti-AS effect was obtained by in vitro gastrointestinal bionic digestion. Further, the anti-AS activity of FMB-BBTI was verified by the classic apoE–/– mice model, characterized by the decreases of the inflammatory cytokines (TNF-α and IL-1β) and atherosclerotic plaque. Importantly, FMB-BBTI remodeled the structure of gut microbiota in apoE–/– mice, including the increase of Firmicutes at the phylum level, and the abundance alteration of five genera at the genus level, especially significant enrichment of Lactobacillus. Collectively, FMB-BBTI markedly restrains the AS progress, suggesting that the remodeling of gut microbiota induced by FMB-BBTI may be the critical factor for its anti-AS activity. This study indicates that FMB-BBTI may serve as a vital functional component contributing to the anti-AS potential of foxtail millet bran.
研究领域:
营养学
·
心血管疾病
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Food & Function
·
2025
·
IF 5.4
Yilong Liu,Ruoqi Wang,Jinren Zhou,Qiang Lyu,Xiaoyong Zhao,Xiaochun Yang,Kunsong Chen,Zhiwei Gao,Xian Li
Atherosclerosis poses a significant threat to global health. This study aimed to investigate the effects of myricetin (MYR) on high-fat diet (HFD)-induced atherosclerosis in ApoE−/− mice. Our findings demonstrated that MYR treatment significantly reduced the formation of atherosclerotic plaques, particularly at a high dose of 100 mg kg−1 day−1. Additionally, MYR markedly attenuated lipid metabolism disorders in ApoE−/− mice by decreasing body weight, improving serum lipid profiles, and reducing lipid deposition. Analysis of 16S rRNA sequencing revealed that MYR treatment enhanced the abundance of probiotic g_Lachnospiraceae_NK4A136, while it reduced that of obesity-associated genera, including Rikenellaceae_RC9_gut_group and Alistipes. Metabolomic analysis and RT-qPCR tests indicated that MYR upregulated hepatic bile acid biosynthesis, evidenced by increased total bile acid levels and enhanced expression of key enzymes CYP7A1 and CYP8B1, particularly through the classical biosynthetic pathway. Spearman's correlation analysis revealed strong associations between the regulated bile acids and these aforementioned bacteria. Therefore, our results demonstrated that MYR exerts an anti-atherosclerotic effect by modulating the gut-liver axis.
研究领域:
药理学
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2012
·Vol. 33
·期 7
·909-917
·
IF 1.953
Wang Xin-ting,Li Jia,Liu Li,Hu Nan,Jin Shi,Liu Can,Mei Dan,Liu Xiao-dong
Aim: Diabetes is associated with elevated serum total cholesterol level and disrupted lipoprotein subfractions. The aim of this study was to examine alterations in the tissue cholesterol contents closely related to diabetic complications. Methods: Intraperitoneal injection of streptozotocin was used to induce type 1 diabetes in adult male Sprague-Dawley rats. On d 35 after the injection, liver, heart, intestine, kidney, pancreas, cerebral cortex and hippocampus were isolated from the rats. The content of total and free cholesterol in the tissues was determined using HPLC. The ATP-binding cassette protein A1 (ABCA1) protein and ApoE mRNA were measured using Western blot and QT-PCR analyses, respectively. Results: In diabetic rats, the level of free cholesterol was significantly decreased in the peripheral tissues, but significantly elevated in hippocampus, as compared with those in the control rats. Diabetic rats showed a trend of decreasing the total cholesterol level in the peripheral tissues, but significant change was only found in kidney and liver. In diabetic rats, the level of the ABCA1 protein was significantly increased in the peripheral tissues and cerebral cortex; the expression of ApoE mRNA was slightly decreased in hippocampus and cerebral cortex, but the change had no statistical significance. Conclusion: Type 1 diabetes decreases the free cholesterol content in the peripheral tissues and increases the free cholesterol content in hippocampus. The decreased free cholesterol level in the peripheral tissues may be partly due to the increased expression of the ABCA1 protein.
研究领域:
内分泌学
·
代谢学
·
药理学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）