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

Bin Chen ¹ Shanshan Sun ² Ling Ge ³ Jialei Fu ³ Wei Nie ¹ Peina Zhou ¹ Peng Cao ³ Qian Zhou ^4*

• ¹ Nanjing Institute for Comprehensive Utilization of Wild Plants, China CO-OP, Nanjing, Jiangsu Province, China
• ² Jiangsu Product Quality Supervision and Inspection Institute, Nanjing, Liaoning Province, China
• ³ Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China
• ⁴ Affliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China

Background: Purslane (Portulaca oleracea) 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, itstherapeitic potential and molecular mechanisms in atherosclerosis (AS) remains 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 in vitro 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 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 in vivo validation, AS was induced in rats through a high-fat diet and carotid artery injury. After 4 weeks of daily POEE administration, therapeutic efficacy was tested by measuring serum lipid levels, cardiac function, histopathological changes and the cholesterorl transport-related protein expression.Results: The bioactive compounds in POEE identified were categorized into 10 groups, including flavonoids (24), terpenoids (16), phenols (6), 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 cells fomation. Furthermore, POEE enhanced reverse cholesterol transport (RCT) by upregulating ATP-binding cassette transporters ABCA1 and ABCG1 to promote cholesterol efflux, while suppressing CD36 and MSR1 to inhibit cholesterol uptake. In vivo, 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 MSR1 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.