Abstract

Hyperlipidemia is a major component of metabolic syndrome, and regarded as one of the main risk factors causing metabolic diseases. We have developed a therapeutic drug, akebia saponin D (ASD), and determined its anti-hyperlipidemia activity and the potential mechanism(s) of action by analyzing the metabolome and intestinal microbiota. Male Sprague-Dawley rats were fed a high fat diet to induce hyperlipidemia, and then given ASD orally for 8 weeks. Lipid levels in serum were determined biochemically. Metabolites in serum, urine and feces were analyzed by UPLC-Q/TOF-MS, and the structure of the intestinal microbiota was determined by 16S rRNA sequencing. The ASD treatment significantly decreased the levels of TC, TG and LDL-c and increased the serum level of HDL-c. Metabolomics analysis indicated that the ASD treatment mainly impacted seven differential metabolites in the serum, sixteen differential metabolites in the urine and four differential metabolites in feces compared to the model group. The ASD treatment significantly changed eight bacteria at the genus level compared to the model group. In conclusion, ASD treatment can significantly alleviate HFD-induced hyperlipidemia and the hypolipidemic effect of ASD treatment is certainly associated with a systematic change in the metabolism, as well as dynamic changes in the structure of the intestinal microbiota.

Highlights

  • Hyperlipidemia is a major public health problem and refers to several serum lipid component abnormalities, including increased levels of triglyceride (TG) and/or total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and decreased high-density lipoprotein cholesterol (HDL-c) [1]

  • The results showed that akebia saponin D (ASD) treatment reversed the variation trend of of almost almost total total 31

  • 2, and we found that treatment can reverse the variation trend of samples, and differential metabolites between the treatment group and model group samples were found, as shown in Table 2, and we found that ASD treatment can reverse the variation trend were found, as shown in

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Summary

Introduction

Hyperlipidemia is a major public health problem and refers to several serum (or plasma) lipid component abnormalities, including increased levels of triglyceride (TG) and/or total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and decreased high-density lipoprotein cholesterol (HDL-c) [1]. Hyperlipidemia is regarded as one of the main risk factors that cause metabolic diseases including atherosclerosis, hypertension, type 2 diabetes and coronary heart disease [2,3]. Used hypolipidemic drugs included statins, fibrates, nicotinic acid, cholesterol absorption inhibitors and bile acid sequestrants [4]. Many of these medications have significant adverse effects, such as Molecules 2019, 24, 1268; doi:10.3390/molecules24071268 www.mdpi.com/journal/molecules Molecules of 21. 22 of and bile acid sequestrants [4]. Many of these medications have significant adverse effects, such as statinbile myopathy, liver injury, and rhabdomyolysis [5,6]. Development and acid sequestrants [4].sleep

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