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Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
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OBJECTIVE: To explore the mechanism of Schisandra lignans for inducing the apoptosis of human glioma SHG-44 neurospheres. METHODS: The effects of Schisandra lignans on the SHG-44 neurospheres proliferation were detected by MTT. The apoptotic rate was analyzed by Annexin-V/PI double staining. The secretion of the bax, bcl-2 and caspase 3 protein was detected by Elisa assay. The expression of bcl-2 protein was examined by Western blot. RESULTS: Schisandra lignans could inhibit the proliferation of SHG-44 neurospheres with the concentration of 50,100,200 mg · L-1 in a dose-dependent manner. Schisandra lignans could induce the apoptosis of SHG-44 neurospheres in a dose-dependent manner. The secretion of bcl-2 was decreased, but ratio of bax/bcl-2 was increased, caspase 3 was increased, the expression of bcl-2 protein was down-regulated. CONCLUSION: Schisandra lignans could induce the apoptosis of human glioma SHG-44 neurospheres. Its mechanism is correlated with down-regulation of the expression of bcl-2 and up-regulation of the ratio of bax/bcl-2, and then activated caspase 3.
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Objective To investigate protective effects of schisandra lignans on doxorubicin-induced liver injury in rats. Methods SD rats were randomly divided into six groups: normal control, model control, vitamin C and schisandra lignans at small, middle, and high doses. The liver injury model was established by intraperitoneal injection of doxorubicin. Normal controls were intragastrically administrated with 0. 9%sodium chloride solution,while other groups were administrated with different medications,respectively. Interleukin-10 (IL-10) in serum,nitric oxide (NO) and aspartate aminotransferase (AST) in liver tissue homogenate were measured. Histopathological changes in hepatic tissues were also observed. Results Serum IL-10 and tissue NO were obviously lower in the model control group than those in other groups,while those in all schisandra lignans treated groups were significantly improved (P<0. 05, P<0. 01). The AST level in schisandra lignans middle- and high dose groups was (372. 58±105. 80) and (327. 92±42. 80) U·g-1 ,respectively,significantly lower than (565. 07±22. 13) U·g-1 in the model control group (P<0. 05,P<0. 01). Histopathological analysis showed that degeneration and necrosis of hepatocytes were remarkably alleviated in all schisandra lignans treated groups. Conclusion Schisandra lignans protect rats against doxorubicin-induced liver injury.
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The main objective of the current study was to develop a universal method for a protein binding assay of complicated herbal components, and to investigate the possible relationship between compound polarity and protein binding using Schisadra lignans as an example. Firstly, the rat, dog and human plasma were spiked with three different concentrations of Schisandra chinensis extract (SLE), and ultramicrofiltration was used to obtain the unbound ingredients. Secondly, thirty-one Schisandra lignans in total plasma and ultrafiltered fluid were measured by LC-IT-TOFMS. Lastly, a relative exposure approach, which entailed calculating the relative concentrations of each Schisandra lignan from the corresponding calibration equation created from the calibration samples spiked with the stock solution of SLE, was applied in order to overcome the absence of authentic standards. The results showed that Schisandra lignans exhibited a high capability to bind with plasma protein, furthermore, the protein binding ratio of the lignan components increased proportionally with their individual chromatographic retention time, which indicated that the ratio of protein binding of lignans might increase accordingly with decreasing polarity. This study suggested that the compound polarity might be an important factor affecting the plasma protein binding of herbal components.