ABSTRACT
As an unhealthy dietary habit, a high-salt diet can affect the body's endocrine system and metabolic processes. As one of the most important metabolites, bile acids can prevent atherosclerosis and reduce the risk of developing cardiovascular diseases. Therefore, in the present study, we aimed to reveal the bile acid metabolism changes in salt-sensitive hypertension-induced vascular endothelial injury. The model was established using a high-salt diet, and the success of this procedure was confirmed by detecting the levels of the blood pressure, vascular regulatory factors, and inflammatory factors. An evaluation of the histological sections of arterial blood vessels and kidneys confirmed the pathological processes in these tissues of experimental rats. Bile acid metabolism analysis was performed to identify differential bile acids between the low-salt diet group and the high-salt diet group. The results indicated that the high-salt diet led to a significant increase in blood pressure and the levels of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α). The high-salt diet causes disorders in bile acid metabolism. The levels of four differential bile acids (glycocholic acid, taurolithocholic acid, tauroursodeoxycholic acid, and glycolithocholic acid) significantly increased in the high-salt group. Further correlation analysis indicated that the levels of ET-1 and TNF-α were positively correlated with these differential bile acid levels. This study provides new evidence for salt-sensitive cardiovascular diseases and metabolic changes caused by a high-salt diet in rats.
ABSTRACT
Hyperlipidemia has become a leading risk factor for cardiovascular diseases and liver injury worldwide. Fructus Phyllanthi (FP) is an effective drug against hyperlipidemia in Traditional Chinese Medicine (TCM) and Indian Medicine theories, however the potential mechanism requires further exploration. The present research aims to reveal the mechanism of FP against hyperlipidemia based on an integrated strategy combining network pharmacology prediction with metabolomics validation. A high-fat diet (HFD)-induced mice model was established by evaluating the plasma lipid levels, including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Network pharmacology was applied to find out the active ingredients of FP and potential targets against hyperlipidemia. Metabolomics of plasma and liver were performed to identify differential metabolites and their corresponding pathways among the normal group, model group, and intervention group. The relationship between network pharmacology and metabolomics was further constructed to obtain a comprehensive view of the process of FP against hyperlipidemia. The obtained key target proteins were verified by molecular docking. These results reflected that FP improved the plasma lipid levels and liver injury of hyperlipidemia induced by a HFD. Gallic acid, quercetin, and beta-sitosterol in FP were demonstrated as the key active compounds. A total of 16 and six potential differential metabolites in plasma and liver, respectively, were found to be involved in the therapeutic effects of FP against hyperlipidemia by metabolomics. Further, integration analysis indicated that the intervention effects were associated with CYP1A1, AChE, and MGAM, as well as the adjustment of L-kynurenine, corticosterone, acetylcholine, and raffinose, mainly involving tryptophan metabolism pathway. Molecular docking ensured that the above ingredients acting on hyperlipidemia-related protein targets played a key role in lowering lipids. In summary, this research provided a new possibility for preventing and treating hyperlipidemia.