Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation.

Aim: The present study was aimed to evaluate the anxiolytic and antidepressant-like effects of schizandrin (from Schisandra chinensis (Turcz.) Baill. which is a functional food) against chronic liver injury in mice.Methods: Chronic liver injury was induced by the treatment of d-galactose (d-GaIN, 200 mg/kg, s.c.) for 8 weeks.Results: Administration of schizandrin (30 mg/kg, i.g.) significantly ameliorated d-GaIN-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), novelty-suppressed feeding test (NSFT), and elevated plus maze (EPM) test. In addition, schizandrin remarkably reduced the oxidative stress due to its potential to enhance the levels of decreased CAT, GSH/GSSG, SOD, and increased MDA in peripheral and brain, the antioxidant activities might be related with the Nrf2/HO-1 pathway. Furthermore, schizandrin could dramatically inhibit the neuroinflammation in mice by reducing pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) through regulating NF-κB/NLRP3/Iba-1 signaling. Besides, the elevated levels of ammonia, AST, and ALT were significantly reduced by schizandrin.Conclusion: The present data revealed that hyperammonemia produced due to liver injury-induced oxidative stress and neuroinflammation in the hippocampus and prefrontal cortex resulting in anxiety and depression were improved by schizandrin.

A new insight on the role of zinc in the regulation of altered thyroid functions during lithium treatment.

BACKGROUND: Lithium salts are widely used for the treatment of mental disorders but cause thyroid dysfunctions while zinc is an essential trace element and is required for a broad range of biological activities. The present study was designed to explore the potential of zinc in regulating 131I biokinetics and thyroid functions following lithium therapy. METHODS: To carry out the investigations, 40 female sprague dawley rats weighing 110-140g were segregated into four groups viz. Group I animals served as untreated controls, group II animals were given lithium (Li2CO31.1 g/kg diet), group III animals were supplemented with zinc (227 mg ZnSO4/L drinking water) and animals in group IV were given a combined treatment of lithium and zinc. The treatments were given for durations of 1, 2 and 4 months. RESULTS: Following intraperitoneal administration of 0.37 MBq carrier- free-131I, a significant depression in the thyroidal 131I uptake both at 2 and 24 hrs was observed following lithium treatment for all the durations which however was brought to within normal levels following zinc supplementation. Lithium treatment caused a significant elevation in the thyroidal biological half lives of 131I which was appreciably attenuated following 2 and 4 months of zinc supplementation. Lithium administration for 2 and 4 months significantly decreased serum T3 and T4 levels which however were increased following zinc supplementation. Lithium treatment for 4 months caused a significant decrease in the thyroidal activities of Na+ K+ ATPase and monoamine oxidase which were brought to near normal levels by zinc. Further, lithium treatment for 4 months raised thyroidal levels of lipid peroxidation and catalase which however were normalized by zinc supplementation. On the contrary, thyroidal levels of reduced glutathione and glutathione S transferase decreased significantly following 2 and 4 months of lithium treatment but were significantly increased following zinc treatment. CONCLUSIONS: The present study concludes that zinc supplementation is helpful in attenuating the adverse effects caused by lithium on thyroid functions and can effectively regulate the biokinetics of 131I.

Supplementing dietary sugar promotes endoplasmic reticulum stress-independent insulin resistance and fatty liver in goose.

It is known that endoplasmic reticulum stress (ERS) contributes to insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD) in mammals. However, we recently demonstrated that overfeeding with a traditional diet (mainly consisting of cooked maize) does not induce ERS in goose. As cellular studies show that high glucose and palmitate can trigger ERS in mammalian cells, we hypothesized that supplementing sugar to the traditional diet could induce ERS, thus promoting insulin resistance and fatty liver. To test the hypothesis, we first treated goose primary hepatocytes with high glucose (25 mM and 50 mM) and palmitate (0.5 mM) supplemented with or without 0.25 mM oleate. Data indicated that, as in mammalian cells, high glucose and palmitate indeed induced ERS in goose primary hepatocytes, and palmitate-induced ERS was suppressed by supplemental 0.25 mM oleate. We then tested the hypothesis with an in vivo study, in which Landes geese overfed with traditional or novel diets (i.e., the traditional diet supplemented with sugar) were compared with control geese (normally fed with cooked maize) for ERS, IR and fatty liver. The differences in glucose tolerance, insulin tolerance and postprandial blood glucose between the geese overfed with traditional and novel diets suggested that supplementing dietary sugar promoted IR. This promotion was accompanied with an increasing trend of liver weight and abdominal fat weight relative to body weight. Surprisingly, compared to overfeeding with the traditional diet, overfeeding with the novel diet did not induce ERS, even further suppressed ERS in goose fatty liver. Together, our findings suggest that supplementing dietary sugar promotes ERS-independent IR and fatty liver in goose. It is intriguing to discover the factor(s) protecting goose liver from ERS as well as the non-ERS mechanism underlying IR.

Bioassay-guided isolation and identification of active compounds from Fructus Arctii against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

Dactylogyrus intermedius is a significant monogenean parasite on the gills of cyprinid fishes and can cause serious problem in fish aquaculture. In the present study, bioassay-guided fractionation was employed to identify the active compounds from Fructus Arctii against D. intermedius. Five solvents (petroleum ether, chloroform, ethyl acetate, ethanol, and water) were applied for the extraction of Fructus Arctii. Among them, only the chloroform extract exhibited promising anthelmintic efficacy and therefore, subjected to the further isolation and purification using various chromatographic techniques. Two compounds showing potent activity were obtained and identified by spectral data (infrared, nuclear magnetic resonance, and mass spectrometry) as: arctigenin (1) and arctiin (2). They were found to be significantly effective against D. intermedius with median effective concentration (EC(50)) values of 0.62 and 3.55 mg L(-1), respectively. Arctigenin exhibited higher activity as compared with the positive control mebendazole with an EC(50) value of 1.25 mg L(-1). The 48-h acute toxicity tests (LC(50)) of arctigenin and arctiin were found to be 8.47 and 14.14 mg L(-1) for goldfish, respectively. These results provided evidence that the studied plant extract, as well as the isolated compounds, might be potential sources of new antiparasitic drug for the control of Dactylogyrus.