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

Abstract

Abstract 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.