Food & Function
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2025
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IF 5.4
Shenji Yang,Xiaojun Huang,Xiajialong Li,Jing Feng,Peng Chen,Zhikang Cao,Luyao He,Chaojun Li,Zhipeng Li,Ming-Yong Xie
Cardiovascular diseases are leading causes of death globally, often manifesting after years of atherosclerosis (AS) progression. In this study, we investigated the atheroprotective effects of three different sources of glucomannan, Dendrobium officinale polysaccharide, Konjac glucomannan, and Aloe vera polysaccharide (AVP) using an in vitro ox-LDL induced foam cell model and an in vivo high-fat high-cholesterol diet-fed ApoE-/- mouse model. Both settings indicate that AVP exerts the most significant atheroprotective effects. It inhibits lipid absorption and enhances the regulation of lipid homeostasis by Liver X Receptor, thereby suppressing the formation of foam cells. It can also alleviate ox-LDL-induced oxidative stress and apoptosis in RAW 264.7 cells. Animal experiments show that AVP can prevent the formation of atherosclerotic plaques and coronary artery fibrosis, while also reducing circulating IL-1β levels. Furthermore, liver transcriptomic analysis shows that AVP inhibits inflammation, and promotes bile acid excretion and transport by upregulating Farnesoid X Receptor. Additionally, metagenomic analysis indicates that AVP can significantly reverse the microbial alterations associated with AS. Specific gut microbes, such as Prevotella, may partially mediate the effects of AVP through the gut-liver axis. This is the first study to report the atheroprotective effects of AVP, demonstrating that it alleviates atherosclerosis by restoring lipid metabolism homeostasis and modulating the gut microbiome.
研究领域:
生物学
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医学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
·
2020
·Vol. 75
·期 4
·321
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IF 2.598
Cao Qian,Du Hongjiao,Fu Xi,Duan Na,Liu Changhe,Li Xiaodong
Artemisinin is an endoperoxide sesquiterpene lactone from Artemisia annua L with multiple beneficial effects, including anti-inflammation, antioxidant, and vascular protection. Recent studies have found that inflammation along with autophagy deficiency in macrophages is the possible reason for foam cell accumulation in the intima, which leads to atherosclerotic plaque formation. The primary aims of this study were to explore the inhibiting effect of artemisinin on atherosclerosis in high-fat diet–fed ApoE −/− mice and investigate the probable mechanism. Artemisinin (50 and 100 mg/kg, intragastric administration) treatment effectively inhibited foamy macrophage transformation and decreased atherosclerotic plaque formation in atherosclerotic mice. Moreover, artemisinin promoted AMP-activated protein kinase (AMPK) activation, inhibited mammalian target of rapamycin (mTOR) and uncoordinated-51-like kinase 1 (ULK1) phosphorylation, and increased LC-3II accumulation and P62 degradation, thereby enhancing macrophage autophagy . Besides, the inhibiting effect of artemisinin on mTOR and ULK1 phosphorylation could be abrogated by AMPK knockdown, suggesting AMPK was the essential target of artemisinin on promoting macrophage autophagy . Our study indicated that artemisinin alleviated atherosclerotic lesions by accelerating macrophage autophagy through the AMPK/mTOR/ULK1 pathway.
研究领域:
药理学
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心血管疾病
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG TARGETING
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2019
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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
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF FOOD SCIENCES AND NUTRITION
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2025
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IF 3.3
Rui Liu,Songxue Wang,Zhifu Liu,Qian Cheng,Qiuyuan Liang,Jian Du,Huali Wang,Ye Zhang,Hao Wang
Selenium-rich yeast (SeY) is a dietary supplement known to confer multiple health benefits, but its effects on HFD-fed ApoE−/− mice were previously unclear. In this study, it was shown that the intervention of SeY could decrease the body weight (7.69%), as well as the levels of both TC and TG for livers (43.36 and 14.50%) and serum (25.34 and 28.67%). Conversely, the HDL-C levels were increased high to 190%, as well as the antioxidant capacity, reflected in the increased levels of the CAT, SOD, and GSH-Px in both the liver (16.93, 22.06, and 17.59%) and the serum (40.67, 113.76, and 19.83%). SeY could further regulate mRNA levels related to lipid synthesis and transport. Moreover, the anti-hyperlipidemic effects of SeY were manifested in enriching SCFAs-producing bacteria, and the cognitive impairment caused by HFD was also alleviated. Overall, all of the results indicated the effect of SeY in regulating abnormal lipid metabolism and developing functional dietary supplements.
研究领域:
营养学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
BMC Nephrology
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2019
·Vol. 20
·期 1
·1-7
·
IF 2.088
Xiong Ruifang,Lu Xiangxue,Song Jinghong,Li Han,Wang Shixiang
Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial.Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta.Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group).Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.
研究领域:
心血管疾病
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分子生物学
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动物模型
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信号转导
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DOI
PubMed
高影响因子
Nanoscale
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2015
·Vol. 7
·期 17
·7682-7691
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IF 7.394
Zhiyou Peng,Jinbao Qin,Bo Li,Kaichuang Ye,Yuxin Zhang,Xinrui Yang,Fukang Yuan,Lijia Huang,Junqing Hu,Xinwu Lu
Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE−/− mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.
研究领域:
生物医学工程
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心血管疾病
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纳米技术
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治疗方法
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产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2024
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IF 6.1
Zhenjie Yu,Huarong Shao,Xintian Shao,Linyan Yu,Yanan Gao,Youxiao Ren,Fei Liu,Caicai Meng,Peixue Ling,Qixin Chen
Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-mussel oligosaccharide (MOS-1) to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed ApoE −/− mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.
研究领域:
药理学
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细胞生物学
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药物开发
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
·
IF 4.8
Jie Du,Xinxin Zhu,Youqi Zhang,Xingtao Huang,Xuedong Wang,Fan Yang,Hongyuan Xia,Jingbo Hou
C1q/TNF-related protein 13 (CTRP13) is a secreted adipokine that has been shown to play an important role in a variety of cardiovascular diseases. However, the effect of CTRP13 on ferroptosis of endothelial cells and its underlying mechanism remain unclear. In the present study, we analyzed the effects of CTRP13 on endothelial dysfunction in high-lipid-induced ApoE −/− mice and ox-LDL-induced mouse aortic endothelial cells (MAECs). In vivo experiment: Male ApoE −/− mice fed high fat were given C1ql3 gene overexpression adeno-associated virus. The atherosclerotic plaque size, lipid content, collagen fiber proportion and iron deposition level were measured. In vitro, CTRP13 combined with ox-LDL was used to pretreat MAECs to detect cell survival rate, lipid peroxidation, iron ion deposition and mitochondrial level. In this study, CTRP13 was found to inhibit ferroptosis of endothelial cells, demonstrated by up-regulated the expression of ferroptosis protective protein glutathione Peroxidase 4 (GPX4), and decreased the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) protein. Mechanistically, gtp cyclohydrolase 1(GCH1) silencing or tetrahydrobiopterin (BH4) inhibiting may counteract the protective effect of CTRP13 on ox-LDL-induced ferroptosis of endothelial cells, which is characterized by decreased cell activity, mitochondrial damage, increased iron ion deposition and lipid peroxidation, decreased GPX4 expression, and increased ACSL4 expression. This study demonstrated for the first time that CTRP13 can improve mitochondrial oxidative stress, inhibit ferroptosis of endothelial cells and improve endothelial cell dysfunction by activating the GCH1/BH4 signaling pathway, thereby inhibiting the progression of atherosclerosis.
研究领域:
心血管疾病
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细胞生物学
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分子生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2021
·
IF 3.905
Lili Tan,Jie Lu,Limin Liu,Lu Li
Atherosclerosis is the underlying contributing factor of cardiovascular disease, which is a process of inflammation and lipid-rich lesion. Macrophage-derived foam cell is a key hallmark of atherosclerosis and connected with various factors of lipid metabolism. Here, we showed that fatty acid binding protein 3 (FABP3) was upregulated in the aorta of ApoE −/- mice with high-fat-diet (HFD) feeding. Knockdown of FABP3 in HFD-fed ApoE −/- mice notably facilitated cholesterol efflux, inhibited macrophage foam cell formation, and thus prevented atherogenesis. Furthermore, FABP3 silencing decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ). Mechanistic studies had disclosed the involvement of PPARγ signaling in balancing cholesterol uptake and efflux and diminishing foam cell formation. These findings firstly revealed an anti-atherogenic role of FABP3 silencing in preventing foamy macrophage formation partly through PPARγ, which might be a beneficial approach for therapying atherosclerosis.
研究领域:
心血管疾病
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脂质代谢
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炎症
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Weixin Li,Zhuqi Huang,Yue Luo,Yaqian Cui,Mingjiang Xu,Wu Luo,Gaojun Wu,Guang Liang
Atherosclerosis (AS) is a chronic inflammatory disease. Recent studies have showed that stimulator of interferon genes (STING), an important protein in innate immunity, mediates pro-inflammatory activation of macrophages in the development of AS. Tetrandrine (TET) is a natural bisbenzylisoquinoline alkaloid isolated from Stepania tetrandra and possesses anti-inflammatory activities, with unknown effects and mechanisms in AS. In this study, we explored the anti-atherosclerotic effects of TET and investigated the underlying mechanisms. Mouse primary peritoneal macrophages (MPMs) are challenged with cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) or oxidized LDL (oxLDL). We found that pretreatment with TET dose-dependently inhibited cGAMP- or oxLDL-induced STING/ TANK-binding kinase 1 (TBK1) signaling, then suppressing nuclear factor kappa-B (NF-κB) activation and pro-inflammatory factor expression in MPMs. ApoE -/- mice were fed a high-fat diet (HFD) to develop an atherosclerotic phenotype. Administration of TET at 20 mg/kg/day significantly reduced HFD-induced atherosclerotic plaques, accompanied with decreased macrophage infiltration, inflammatory cytokine production, fibrosis, and STING/TBK1 activation in aortic plaque lesions. In summary, we demonstrate that TET inhibits STING/TBK1/NF-κB signaling pathway to reduce inflammation in oxLDL-challenged macrophages and alleviate atherosclerosis in HFD-fed ApoE -/- mice. These findings proved that TET could be a potential therapeutic candidate for the treatment of atherosclerosis-related diseases.
研究领域:
心血管疾病
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免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Cell Death & Disease
·
2021
·Vol. 12
·期 1
·1-18
·
IF 8.469
Fang Shaohong,Wan Xin,Zou Xiaoyi,Sun Song,Hao Xinran,Liang Chenchen,Zhang Zhenming,Zhang Fangni,Sun Bo,Li Hulun,Yu Bo
Inducing autophagy and inhibiting apoptosis may provide a therapeutic treatment for atherosclerosis (AS). For the treatment of progressive AS, arsenic trioxide (ATO) has been used to coat vascular stents. However, the effect of ATO on autophagy of macrophages is still unknown. Therefore, the aims of this study were to characterize the effects and the mechanism of actions of ATO on autophagy in macrophages. Our results showed that ATO-induced activation of autophagy was an earlier event than ATO-induced inhibition of the expression of apoptosis markers in macrophages and foam cells. Nuclear transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy and promoting lysosomal biogenesis. Here, we report that ATO triggered the nuclear translocation of TFEB, which in turn promoted autophagy and autophagosome-lysosome fusion. Both the latter events were prevented by TFEB knockdown. Moreover, ATO decreased the p-AKT and p-mTOR in the PI3K/AKT/mTOR signaling pathway, thus inducing autophagy. Correspondingly, treatment with the autophagy inhibitor 3-methyladenine (3-MA) abolished the autophagy-inducing effects of ATO. Meanwhile, PI3K inhibitor (LY294002) and mTOR inhibitor (rapamycin) cooperated with ATO to induce autophagy. Furthermore, reactive oxygen species (ROS) were generated in macrophages after treatment with ATO. The ROS scavenger N-acetyl-1-cysteine (NAC) abolished ATO-induced nuclear translocation of TFEB, as well as changes in key molecules of the AKT/mTOR signaling pathway and downstream autophagy. More importantly, ATO promoted autophagy in the aorta of ApoE −/− mice and reduced atherosclerotic lesions in early AS, which were reversed by 3-MA treatment. In summary, our data indicated that ATO promoted ROS induction, which resulted in nuclear translocation of TFEB and inhibition of the PI3K/AKT/mTOR pathway. These actions ultimately promoted macrophage autophagy and reduced atherosclerotic lesions at early stages. These findings may provide a new perspective for the clinical treatment of early-stage atherosclerosis and should be further studied.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Yun Wang,Jiawei Wu,Jiaying Zhu,Chujie Ding,Wanfeng Xu,Haiping Hao,Jun Zhang,Guangji Wang,Lijuan Cao
Ethnopharmacological relevance The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. Aim of this study This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. Materials and methods The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe −/− mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. Results SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe −/− mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A 2 (sPLA 2 ) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. Conclusions Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.
研究领域:
药理学
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心血管疾病
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传统中药
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代谢组学
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脂质组学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）