The mechanism of effective components compatibility of Astragalus and Nelumbinis folium on the prevention and treatment of dyslipidemia by regulating cholesterol reversal transport

Background: Astragalus saponins (AS) and Nelumbinis folium alkaloids (NFA) are the main active components of Astragalus membranaceus and Nelumbo nucifera Gaertn . This research investigated the beneficial effects and mechanisms of AS-NFA in preventing and treating dyslipidemia. Methods Rats were fed a high-fat diet (HFD) for to establish a dyslipidemia model and HepG2 cells were induced by cholesterol and 25-hydroxycholesterol to establish a steatosis cell model, treating with AS-NFA. The levels of blood lipids and liver function were detected by automatic biochemical analyzer. HE staining and oil red O staining were used to observe the pathological morphological changes and steatosis. The uptake of Dil-HDL by HepG2 cells was observed and detected by fluorescence microscopy. The mRNA and protein expression levels of Cholesterol reverse transport (RCT)-related mRNA and protein. in rat liver and HepG2 cells were detected by RT-PCR, immunofluorescent staining and Western Blot. Results AS-NFA had remarkable effects on regulating blood lipids, improving liver function, alleviating pathological injury of liver tissues, and reducing hepatic lipid accumulation. AS-NFA dramatically reduced total cholesterol (TC), total bile acid (TBA) levels, and lipid accumulation, and increased the intake of HDL in HepG2 cells. AS-NFA can regulate RCT by upregulating scavenger receptor class B type 1 (SR-B1), recombinant cytochrome P450 7A1 (CYP7A1), and farnesoid X receptor (FXR) in the HFD rats and HepG2 steatosis cells. The effects of AS-NFA on the SR-B1/CYP7A1/FXR signaling pathway were abolished when SR-B1 was inhibited by BLT-1 (a selective SR-B1 inhibitor) in HepG2 cells. Conclusion AS-NFA has an efficient lipid-regulating effect mediated by activation of the SR-B1/CYP7A1/FXR signaling pathway to regulate RCT. Our findings provide new insight and evidence for the discovery of a new lipid-regulating drug for the prevention and treatment of dyslipidemia in the clinic.