BackgroundThe aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum.Material/MethodsForty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels.ResultsTreatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney.ConclusionsGPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

Objective. The purpose of this study was to explore the potential mechanisms of the lipid-regulating effects and the effect on modulating the gut microbiota of hawthorn leaf flavonoids (HLF) in the high-fat diet-induced hyperlipidemic rats. Methods. The hypolipidemic effect of HLF was investigated in the high-fat diet-induced hyperlipidemic rats. The action targets of HLF in the treatment of hyperlipidemia were predicted by network pharmacology and KEGG enrichment bubble diagram, which were verified by the test of western blotting. Meanwhile, we used 16S rRNA sequencing to evaluate the effects of HLF on the microbes. Results. The results of animal experiments showed that HLF could reduce the body weight and regulate the levels of serum lipid in high-fat diet (HFD) rats. Meanwhile, for the related targets of cholesterol metabolism, HLF could significantly upregulate the expression of LDLR, NR1H3, and ABCG5/ABCG8; reduce the expression of PCSK9; and increase the level of CYP7A1 in the intestinal tissue, whereas cholesterol biosynthetic protein expressions including HMGCR and SCAP were lowered by HLF. In addition, HLF increased the activities of plasma SOD, CAT, and GSH-Px and decreased the levels of Casp 1, NLRP3, IL-1β, IL-18, and TNF-α, improving the degree of hepatocyte steatosis and inflammatory infiltration of rats. Notably, HLF significantly regulated the relative abundance of major bacteria such as g_Lactobacillus, g_Anaerostipes, g_[Eubacterium]_hallii_group, g_Fusicatenibacter, g_Akkermansia, and g_Collinsella. Synchronously, we found that HLF could regulate the disorder of plasma HEPC and TFR levels caused by HFD. Conclusion. This study demonstrates that HLF can regulate metabolic hyperlipidemia syndromes and modulate the relative abundance of major bacteria, which illustrated that it might be associated with the modulation of gut microbiota composition and metabolites.

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