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L.的乙醇提取物通过调节胆固醇流出和摄取途径减轻动脉粥样硬化。

Ethanol extract of L. mitigates atherosclerosis through modulation of cholesterol efflux and uptake pathways.

作者信息

Chen Bin, Sun Shanshan, Fu Jialei, Ge Ling, Nie Wei, Zhou Peina, Cao Peng, Zhou Qian

机构信息

Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Institute of Plant Resources and Chemistry, Nanjing Research Institute for Comprehensive Utilization of Wild Plants, Nanjing, China.

出版信息

Front Pharmacol. 2025 Mar 19;16:1550812. doi: 10.3389/fphar.2025.1550812. eCollection 2025.

DOI:10.3389/fphar.2025.1550812
PMID:40176886
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11961987/
Abstract

BACKGROUND

Purslane () is a medicinal and edible plant. Purslane extract (POEE) exhibits lipid-lowering, anti-inflammatory, and antioxidant properties. Traditionally, this extract has been used to treat various inflammatory conditions, including skin inflammation, enteritis, and dysentery. However, its therapeutic potential and molecular mechanisms in atherosclerosis (AS) remain unclear.

METHODS

Ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and the Traditional Chinese Medicine Systems Pharmacology Database were employed to identify the active components of POEE. Network pharmacology was used to predict POEE's mechanisms for alleviating AS. An foam cell model was established by treating RAW264.7 macrophages with oxidized low-density lipoprotein (ox-LDL), and the protective effects of POEE were assessed via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, while intracellular lipid accumulation was identified using Oil Red O staining. Protein expression related to cholesterol metabolism was analyzed by Western blot (WB). For validation, AS was induced in rats through a high-fat diet and carotid artery injury. After 4 weeks of daily POEE administration, the therapeutic efficacy was tested by measuring serum lipid levels, cardiac function, histopathological changes, and the cholesterol transport-related protein expression.

RESULTS

The bioactive compounds identified in POEE were categorized into 10 groups, including flavonoids (24), terpenoids (16), phenols (6), and alkaloids (4), and others. Network pharmacology predictions implicated POEE in modulating the "Lipid and Atherosclerosis" pathway. POEE significantly reduced total cholesterol (TC) and free cholesterol (FC) levels in ox-LDL-stimulated macrophages, attenuating foam cell formation. Furthermore, POEE enhanced reverse cholesterol transport (RCT) by upregulating the expressions of ATP-binding cassette transporters ABCA1 and ABCG1 to promote cholesterol efflux, while suppressing CD36 and MSR1 expressions to inhibit cholesterol uptake. , POEE administration lowered serum triglycerides (TG), TC, FC, and LDL-C levels; elevated HDL-C; and ameliorated carotid artery lesions in AS rats. Concordantly, ABCA1 expression was upregulated and that of MSR1 was downregulated in POEE-treated carotid tissues.

CONCLUSION

POEE alleviates atherosclerosis by enhancing RCT through regulation of cholesterol efflux and uptake pathways. POEE may be a promising therapeutic candidate for AS.

摘要

背景

马齿苋是一种药食两用植物。马齿苋提取物(POEE)具有降脂、抗炎和抗氧化特性。传统上,这种提取物已被用于治疗各种炎症性疾病,包括皮肤炎症、肠炎和痢疾。然而,其在动脉粥样硬化(AS)中的治疗潜力和分子机制仍不清楚。

方法

采用超高效液相色谱-四极杆/飞行时间质谱(UPLC-Q/TOF-MS)和中药系统药理学数据库鉴定POEE的活性成分。利用网络药理学预测POEE缓解AS的机制。通过用氧化低密度脂蛋白(ox-LDL)处理RAW264.7巨噬细胞建立泡沫细胞模型,并通过3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(MTT)法评估POEE的保护作用,同时使用油红O染色鉴定细胞内脂质积累。通过蛋白质印迹法(WB)分析与胆固醇代谢相关的蛋白质表达。为进行体内验证,通过高脂饮食和颈动脉损伤在大鼠中诱导AS。在每天给予POEE 4周后,通过测量血清脂质水平、心脏功能、组织病理学变化以及与胆固醇转运相关的蛋白质表达来测试治疗效果。

结果

在POEE中鉴定出的生物活性化合物分为10类,包括黄酮类(24种)、萜类(16种)、酚类(6种)、生物碱类(4种)等。网络药理学预测表明POEE参与调节“脂质与动脉粥样硬化”途径。POEE显著降低ox-LDL刺激的巨噬细胞中的总胆固醇(TC)和游离胆固醇(FC)水平,减轻泡沫细胞形成。此外,POEE通过上调ATP结合盒转运蛋白ABCA1和ABCG1的表达来促进胆固醇流出,从而增强逆向胆固醇转运(RCT),同时抑制CD36和MSR1的表达以抑制胆固醇摄取。在体内,给予POEE可降低AS大鼠的血清甘油三酯(TG)、TC、FC和低密度脂蛋白胆固醇(LDL-C)水平;提高高密度脂蛋白胆固醇(HDL-C)水平;并改善颈动脉病变。与此一致,在POEE处理的颈动脉组织中,ABCA1表达上调而MSR1表达下调。

结论

POEE通过调节胆固醇流出和摄取途径增强RCT来减轻动脉粥样硬化。POEE可能是AS的一种有前景的治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/584955509cd5/fphar-16-1550812-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/3893ecd4af08/fphar-16-1550812-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/ab7b0ee58258/fphar-16-1550812-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/5b664e60a9e9/fphar-16-1550812-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/165ba27627ab/fphar-16-1550812-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/2bfba422930a/fphar-16-1550812-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/584955509cd5/fphar-16-1550812-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/3893ecd4af08/fphar-16-1550812-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/ab7b0ee58258/fphar-16-1550812-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/5b664e60a9e9/fphar-16-1550812-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/165ba27627ab/fphar-16-1550812-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/2bfba422930a/fphar-16-1550812-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5334/11961987/584955509cd5/fphar-16-1550812-g006.jpg

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