Abstract
Astragalus membranaceus (AM) is a food and medicinal homologous plant. The current research is aimed to investigate the beneficial effects and mechanisms of AM in treating acquired hyperlipidemia. The network pharmacology and bioinformatics analysis results showed 481 AM-related targets and 474 acquired hyperlipidemia-associated targets, and 101 candidate targets were obtained through the intersection, mainly enriched in endocrine resistance, AGE-RAGE in diabetic complications and p53 signaling pathways. Quercetin, kaempferol, calycosin, formononetin and isorhamnetin were determined as the candidate active components of AM in the treatment of acquired hyperlipidemia. Moreover, key targets of AM, namely, AKT serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), cyclin D1 (CCND1) and estrogen receptor 1 (ESR1), were screened out, which were closely related to adipogenesis, fatty acid metabolism and bile acid metabolism. The subsequent animal experiments showed that AM extract treatment improved the lipid profiles of the high-fat diet (HFD)-fed mice by reducing lipogenesis and increasing lipolysis and lipid β-oxidation, which were associated with the downregulating of AKT1 and CCND1, and the upregulating of VEGFA and ESR1 in liver and adipose tissue. Overall, AM alleviated acquired hyperlipidemia through regulating lipid metabolism, and AKT1, VEGFA, CCND1 and ESR1 might be the key targets.
Highlights
With the change of diet and lifestyle, the incidence rate of acquired hyperlipidemia increases year by year
Compared with that in adipose tissues of mice fed with low-fat diet (LFD), the expression of AKT serine/threonine kinase 1 (AKT1) and cyclin D1 (CCND1) in those of mice fed with high-fat diet (HFD) was significantly upregulated, while the expression of vascular endothelial growth factor A (VEGFA) and estrogen receptor 1 (ESR1) was significantly downregulated
We found that the levels of AKT1 and CCND1 protein were increased significantly, and the levels of VEGFAleavnedlsEoSf Rth1e apbroovteeifnouwr ekreey dtaergcreetsaisnedlivseirgtnisisfuiceaanntdlyWinATthoef mHiFceDfegdrwouitph HcoFmD.-We found pared with the NthDatgtrhoeulpev. eFlsurotfhAerKmT1oraen,dACKCTN1Da1npdroCtCeiNn Dw1ereprinoctereinaseledvseilgsnwifiecraentslyig, annifdi-the levels cantly increased,oafnVdEtGhFeAleavnedlsEoSfRV1EpGroFtAeinanwderEeSdRe1crperaosetedinsigwneifirecasnigtlnyifinicathnetlHy FdDecgrreoausepdcompared with the normal diet group (ND) group
Summary
With the change of diet and lifestyle, the incidence rate of acquired hyperlipidemia increases year by year. Due to the low toxic side effects, natural active substances derived from plants or food have been highlighted in treating chronic metabolic disease [4,5]. These plant extracts can regulate lipid metabolism through multi-component and multi-target regulatory networks [6,7]. In view of the above findings, it is of a certain value to explore the main active components and targets of AM in the treatment of acquired hyperlipidemia. An “AMcomponent-target” network was constructed to clarify the active components, main signal pathways and key targets of AM in the treatment of acquired hyperlipidemia.
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