BackgroundHyperlipidemia is a major component of metabolic syndrome, and often predicts cardiovascular diseases. We developed a new therapeutic agent berberine compounds (BC), consisting of berberine, oryzanol and vitamin B6, and determined their anti-hyperlipidemia activity and underlying mechanisms.MethodsMale Wistar rats were fed a high fat diet (HFD) to induce hyperlipidemia, and then given BC orally for 4 weeks. Body weight and food intake were recorded weekly, and lipid profiles in serum were determined biochemically. Metabolites in serum, urine, liver and feces were analyzed by GC–MS, and the structure of microbiota was determined by 16S rDNA sequencing.ResultsLipid lowering was observed in the hyperlipidemic rats upon BC treatment without apparent adverse side effects. Metabolomics analysis indicated that the BC treatment resulted in increased pyruvic acid, serotonin, and ketogenic and glycogenic amino acid levels in the serum, increased pyridoxine and 4-pyridoxic acid in the urine, decreased hypotaurine and methionine in the liver, and increased putrescine and decreased deoxycholate and lithocholate in feces. The BC treatment also resulted in an enrichment of beneficial bacteria (e.g. Bacteroides, Blautia) and a decrease in Escherichia.ConclusionsThe lipid lowering effect of BC treatment in hyperlipidemic rats is associated with a global change in the metabolism of lipids, carbohydrates and amino acids, as well as the structure of microbiota.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0987-5) contains supplementary material, which is available to authorized users.

AIMTo elucidate the potential role of autophagy and the protective effects of Jiang Zhi Granule (JZG) in metabolic stress-induced hepatocyte injury.METHODSAn in vitro and in vivo approach was used in this study. HepG2 cells were incubated in culture medium containing palmitate (PA; 0, 0.1, 0.2, 0.3, 0.4 or 0.5 mmol/L) and treated with or without JZG (100 μg/mL) for 24 h or 48 h, and the progression of autophagy was visualized by stable fluorescence-expressing cell lines LC3 and p62. Western blot analyses were performed to examine the expression of LC3-II/LC3-I, p62, mTOR and PI3K, while mitochondrial integrity and oxidative stress were observed by fluorescence staining of JC-1 and reactive oxygen species. C57BL/6 mice were divided into three groups: control group (n = 10), high fat (HF) group (n = 13) and JZG group (n = 13); and, histological staining was carried out to detect inflammation and lipid content in the liver.RESULTSThe cell trauma induced by PA was aggravated in a dose- and time-dependent manner, and hepatic function was improved by JZG. PA had dual effects on autophagy by activating autophagy induction and blocking autophagic flux. The PI3K-AKT-mTOR signaling pathway and the fusion of isolated hepatic autophagosomes and lysosomes were critically involved in this process. JZG activated autophagy progression by either induction of autophagosomes or co-localization of autophagosomes and lysosomes as well as degradation of autolysosomes to protect against PA-induced hepatocyte injury, and protected mitochondrial integrity against oxidative stress in PA-induced mitochondrial dysfunction. In addition, JZG ameliorated lipid droplets and inflammation induced by HF diet in vivo, leading to improved metabolic disorder and associated liver injury in a mouse model of non-alcoholic fatty liver disease (NAFLD).CONCLUSIONMetabolic stress-induced hepatocyte injury exhibited dual effects on autophagy and JZG activated the entire process, resulting in beneficial effects in NAFLD.

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BackgroundNonalcoholic steatohepatitis (NASH), the advanced stage of nonalcoholic fatty liver disease that is characterized by both steatosis and severe injury in liver, still lacks efficient treatment. The traditional Chinese formula Salvia–Nelumbinis naturalis (SNN) is effectively applied to improve the symptoms of nonalcoholic simple fatty liver (NAFL) patients. Previous studies have confirmed that SNN could reduce the liver lipid deposition and serum transaminases of NAFL experimental models. This study aims to determine whether SNN is effective for murine NASH model and investigate the underlying pharmacological mechanisms.MethodsC57BL/6 J mice were fed with methionine- and choline-deficient (MCD) diet for six weeks to induce NASH. Simultaneously, SNN or saline was intragastrically administered daily to the mice in the SNN or model group, respectively. A standard diet was given to the control mice. Serum biochemical indices and tumor necrosis factor-α were measured. Liver histopathology was observed, and the contents of triglycerides and lipid peroxide malondialdehyde (MDA) in liver homogenates were evaluated. The hepatic expression and/or activation of genes associated with inflammation, apoptosis, and oxidative stress were determined by quantitative RT-PCR or Western blot analysis.ResultsThe prominent liver steatosis displayed in the NASH model was prevented by SNN. The liver injury of NASH mice was obviously manifested by the increased levels of serum transaminases and bilirubin, as well as the lobular inflammation, elevated pro-inflammatory cytokines, and upregulated apoptosis in liver tissues. SNN administration improved the aforementioned pathological changes. The increased hepatic levels of MDA and cytochrome P450 2E1 of the model confirmed the unregulated balance of oxidative stress. The hepatic expression of nuclear factor erythroid 2-related factor 2 and its target genes decreased, whereas c-Jun N-terminal kinase activation in the model mice increased. Treating the mice with SNN significantly improved oxidative stress-related harmful factors.ConclusionsThis study shows that SNN can protect the liver from severe steatosis and damage induced by MCD diet, which suggests the potential use of SNN on the treatment of NASH patient. The results also indicate that improving the hepatic antioxidant capability of the liver may contribute to the underlying hepatoprotective mechanism.