Fatty liver diseases, mechanisms, and potential therapeutic plant medicines.

The liver is an important metabolic organ and controls lipid, glucose and energy metabolism. Dysruption of hepatic lipid metabolism is often associated with fatty liver diseases, including nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD) and hyperlipidemia. Recent studies have uncovered the contribution of hormones, transcription factors, and inflammatory cytokines to the pathogenesis of dyslipidemia and fatty liver diseases. Moreover, a significant amount of effort has been put to examine the mechanisms underlying the potential therapeutic effects of many natural plant products on fatty liver diseases and metabolic diseases. We review the current understanding of insulin, thyroid hormone and inflammatory cytokines in regulating hepatic lipid metabolism, focusing on several essential transcription regulators, such as Sirtuins (SIRTs), Forkhead box O (FoxO), Sterol-regulatory element-binding proteins (SREBPs). We also discuss a few representative natural products with promising thereapeutic effects on fatty liver disease and dyslipidemia.

Selenium-enriched Bifidobacterium longum protected alcohol and high fat diet induced hepatic injury in mice.

The objective of this study was to verify the protective effect of Bifidobacterium longum (BL) and the synergistical effect of Selenium and BL on alcohol plus high fat diet (HFD) induced hepatic injury in mice. We also want to explore the mechanism of Selenium-enriched Bifidobacterium longum (SeBL). C57BL/6 mice were treated with alcohol plus HFD with or without different dosage of BL or SeBL for 4 weeks. Serum levels of ALT, AST, TC, TG, LDL-C, HDL-C, FFAs, TNF-α, IL-6 and IL-1ß, hepatic MDA level, SOD activity, the mRNA levels of AMPK, PPAR-α and SREBP1 were invested. SeBL inhibited lipid accumulation in hepatocytes; reduced serum AST and ALT levels; improved dyslipidemia; decreased serum FFAs, TC, TG and LDL-C levels. SeBL also inhibited alcohol plus HFD-induced hepatocyte oxidative stress through decrease in hepatic MDA levels and increase in SOD activity. SeBL also regulated lipid metabolism related genes such as AMPK, PPAR-α and SREBP1. Although BL had similar effect as SeBL, SeBL is more effective than BL. SeBL protected mice from alcohol plus HFD-induced hepatic injury in mice because of its inhibitory effect on hepatocellular oxidative stress, lipogenesis and inflammation. Selenium enhanced the protective effect of BL.

Effect of three Napier grass varieties on phytoextraction of Cd- and Zn-contaminated cultivated soil under mowing and their safe utilization.

The use of Napier grass to remediate heavy metal-contaminated soil is a new phytoremediation technique. The objective of this study was to evaluate the ability of Napier grass (Pennisetum purpureum Schumach.) to remediate Cd- and Zn-contaminated cultivated soil under nonmowing and mowing and the possibility of safe utilization of the stem and leaf after detoxification by liquid extraction. Three Napier grass varieties, P. purpureum cv. Mott (PM), P. purpureum cv. Red (PR), and P. purpureum cv. Guiminyin (PG), were planted in a field with 3.74 mg kg-1 Cd and 321.26 mg kg-1 Zn for 180 days. The maximum amounts of Cd and Zn removed by PG were 197.5 and 5023.9 g ha-1, respectively, almost equaling those of hyperaccumulators. Compared with nonmowing, mowing did not decrease the Cd and Zn contents in various tissues but increased the biomasses of PM, PR, and PG by 86.6%, 18.9%, and 26.1%, respectively. Compared with nonmowing, the amounts of Cd removed by PM, PR, and PG under mowing increased by 110.5%, 40.0%, and 107.9%, respectively, and that of Zn increased by 63.0%, 53.1%, and 71.6%. The dominant Cd and Zn chemical fractions in Napier grass were the pectate- and protein-integrated fractions. After liquid extraction, although the nutrient element (Ca, K, Mg, and Mn) contents in the stem and leaf were reduced significantly, the Cd and Zn contents decreased below the limit of the Chinese Hygienic Standard for Feeds, and the crude protein content was largely retained. Such detoxified stems and leaves can be safely used as feeds or as raw materials for energy production.

Methane explosion suppression characteristics based on the NaHCO3/red-mud composite powders with core-shell structure.

The NaHCO3/red-mud (RM) composite powders were successfully prepared by the solvent-anti-solvent method for methane explosion suppression. The RM was used as a carrier, and the NaHCO3 was used as a loaded inhibitor. The NaHCO3/RM composite powders showed a special core-shell structure and excellent endothermic performance. The suppression properties of NaHCO3/RM composite for 9.5% CH4 explosion were tested in a 20L spherical explosion vessel and a 5L Perspex duct. The results showed that the NaHCO3/RM composite powders displayed a much better suppression property than the pure RM or NaHCO3 powders. The loading amount of NaHCO3 has an intensive influence on the inhibition property of NaHCO3/RM composite powders. The best loaded content of NaHCO3 is 35%. It exhibited significant inhibitory effect that the explosion max-pressure declined 44.9%, the max-pressure rise rate declined 96.3% and the pressure peak time delayed 366.7%, respectively.

[Effects of selenium valence states and application concentrations on plant growth, ascorbate-glutathione cycle in Citrus junos cv. Ziyang Xiangcheng]. / 硒的价态与浓度对香橙幼苗生长和AsA-GSH循环的影响.

Potted Citrus. junos cv. Ziyang Xiangcheng seedlings were used to study the effects of selenium (Se) valence states (Se6+ and Se4+) on plant growth and antioxidants and antixodases in ascorbate(AsA)-glutathione (GSH) cycle. The results showed that Se6+ and Se4+ (from 1.0 mg·L-1 to 8.0 mg·L-1) stimulated the seedling growth by increasing plant height, leaf areas, and fresh or dry mass. Applying Se6+significantly increased plant Se levels mainly in leaf, and applying Se4+ slightly increased Se content mainly in root. Certain valence states and concentrations of Se increased leaf chlorophyll and hydrogen peroxide (H2O2) content. Se6+≤2.0 mg·L-1 treatments enhanced the activates of glutathione reductase (GR) and glutathione peroxidase (GPX), and the contents of GSH and oxidized glutathione (GSSG), while Se6+≥4.0 mg·L-1 treatments reduced the antioxidant contents and antixodase activities of GSH cycle. Moreover, Se4+≤ 2.0 mg·L-1 treatments increased the activities of dehydroascorbate reductase (DHAR) and ascorbate peroxidase (APX), and resulted in higher AsA/[AsA+dehydroascorbic acid (DHA)] ratio. When Se4+≥4.0 mg·L -1, the antioxidant contents and antixodase activities of GSH cycle were increased. Together, this study showed that different valence states and application concentrations of Se showed different influences on AsA-GSH cycle in citrus, and 2.0 mg·L-1 Se6+ and 4.0 mg·L-1 Se4+ were the best concentrations for plant growth.

Ethanol promotes saturated fatty acid-induced hepatoxicity through endoplasmic reticulum (ER) stress response.

Serum palmitic acid (PA), a type of saturated fatty acid, causes lipid accumulation and induces toxicity in hepatocytes. Ethanol (EtOH) is metabolized by the liver and induces hepatic injury and inflammation. Herein, we analyzed the effects of EtOH on PA-induced lipotoxicity in the liver. Our results indicated that EtOH aggravated PA-induced apoptosis and lipid accumulation in primary rat hepatocytes in dose-dependent manner. EtOH intensified PA-caused endoplasmic reticulum (ER) stress response in vitro and in vivo, and the expressions of CHOP, ATF4, and XBP-1 in nucleus were significantly increased. EtOH also increased PA-caused cleaved caspase-3 in cytoplasm. In wild type and CHOP(-/-) mice treated with EtOH and high fat diet (HFD), EtOH worsened the HFD-induced liver injury and dyslipidemia, while CHOP knockout blocked toxic effects of EtOH and PA. Our study suggested that targeting UPR-signaling pathways is a promising, novel approach to reducing EtOH and saturated fatty acid-induced metabolic complications.

Inflammatory factors that contribute to upregulation of ERG and cardiac arrhythmias are suppressed by CPU86017, a class III antiarrhythmic agent.

The aim of this study was to verify whether exaggerated arrhythmogenesis is attributed to inflammatory factors actively involving an excess of reactive oxygen species (ROS), transforming growth factor (TGF)-beta and endothelin (ET). We hypothesized that CPU86017, derived from berberine, which possesses multi-channel blocking activity, could suppress inflammatory factors, resulting in inhibition of over-expression of ether-a-go-go (ERG) and an augmented incidence of ventricular fibrillation (VF) in ischaemia/reperfusion (I/R). Rats with cardiomyopathy (CMP) induced by thyroxine (0.2 mg(-1)kg(-1) s.c. daily for 10 days) were treated with propranolol (10 mgkg(-1) p.o.) or CPU86017 (80 mgkg(-1) p.o.) on days 6-10. On the 11th day, arrhythmogenesis of the CMP was evaluated by I/R. In the CMP control group, an increase in VF incidence was found with the I/R episode, accompanied by increased ROS, which manifested as an increased level of malondialdehyde and decreased activities of SOD, glutathione peroxidase and catalase in the myocardium. Levels of inducible nitric oxide synthase and TGF-beta mRNA were increased in association with upregulation of preproET-1 and ET-converting enzyme. We found increased levels of ERG, which correlated well with arrhythmogenesis. Treatment with CPU86017 or propranolol reversed these changes. These experiments verified our hypothesis that the inflammatory factors ROS, iNOS, TGF-beta and ET-1 are actively involved in upregulation of ERG and arrhythmogenesis. CPU86017 and propranolol reduced VF by suppressing these inflammatory factors in the myocardium.

Astilbin inhibits the adhesion of T lymphocytes via decreasing TNF-alpha and its associated MMP-9 activity and CD44 expression.

Our previous study has revealed that astilbin, a flavonoid isolated from the rhizome of Smilax glabra, improves an immunological liver injury and its mechanism includes an inhibition of the lymphocyte adhesion. The present study further examined the anti-adhesive activity in various assays by using human leukemia T cell line Jurkat cells. We found that astilbin inhibited the adhesion of Con A or PMA-activated Jurkat cells to fibronectin, type IV collagen, hyaluronic acid, and [corrected] ECV-304 cells. Astilbin inhibited the adhesion of Jurkat cells to PMA-activated but not non-activated ECV-304 cells without any influence on the survival of the ECV-304 cells and Jurkat cells. Astilbin also inhibited the CD44 expression and TNF-alpha production in Jurkat cells. In the co-culture assay between Jurkat cells and ECV-304 cells, the MMP-9 secretion from Jurkat cells was inhibited after astilbin-treatment, while the exogenous TNF-alpha increased the MMP-9 secretion in a dose-dependent manner. These findings suggest that the inhibition of T lymphocyte adhesion by astilbin may be related to the reduction of the CD44 expression and TNF-alpha production in the cells, which may further cause a decreased MMP-9 secretion.

A novel synthetic oleanolic acid derivative with amino acid conjugate suppresses tumour growth by inducing cell cycle arrest.

Oleanolic acid (3beta-hydroxy-olean-12-en-28-oic acid; OA) has a wide variety of bioactivities and is used for medicinal purposes in many Asian countries. Various derivatives of OA have been synthesized in attempts to improve the potency. Here we describe the anti-tumour activity of a novel OA derivative, N-[(3beta)-3-(acetyloxy)-28-oxoolean-12-en-28-yl]-glycine methyl ester (AOA-GMe). AOAGMe was a more potent inhibitor of the growth of B16 melanoma cells than its parent compound OA, both in-vitro and in-vivo. AOA-GMe also exhibited dose-dependent inhibition of human K562 leukaemia cells, but had almost no toxicity in normal human peripheral blood mononuclear cells. AOA-GMe induced cell cycle arrest in G0/G1 and blocked G1-S transition, which correlated well with marked decreases in levels of cyclin D, cyclin-dependent kinase CDK4 and phosphorylated retinoblastoma protein, and increases in the cyclin-dependent kinase inhibitor p15. OA did not show such activities. These results suggest that AOA-GMe may induce growth arrest in tumour cells through regulation of proteins involved in the cell cycle.