Effects of lentinan on dendritic cell metabolism / 中国药理学通报

Aim To study the effects of lentinan(LNT)on the metabolism of dendritic cells(DCs)by metabonomics, and uncover the potential mechanism of its regulation of DC function. Methods DC2.4 cells were co-incubated with LNT for 24 h, and the activity of the cells was detected by thiazolyl blue tetrazolium bromide(MTT)assay. The contents of interleukin-6(IL-6), tumor necrosis factorα(TNF-α)and interleukin-12(IL-12)in supernatant were detected by enzyme-linked immunosorbent assay(ELISA). The metabolic general changes of DC2.4 cells were detected by Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS), and the differential metabolites were analyzed by multi-distance covariates and bioinformatics, partial least squares-discriminant analysis(PLS-DA). Finally, metabolic pathway analysis was performed by MetaboAnalyst 5.0. Results LNT did not significantly inhibit the activity of DC2.4 cells at the dose of 25100 mg·L-1. LNT(100 mg·L-1)could significantly stimulate the secretion of IL-6, TNF-α and IL-12 in DC2.4 cells. 20 differential metabolites were identified in DC2.4 cells after being stimulated by LNT(100 mg·L-1), which involved 25 metabolic pathways including urea cycle, arginine and proline metabolism. Conclusion The regulation of LNT on DC function involves a variety of amino acid metabolism.

Acutely applied melatonin prevents CCl4-induced testicular lesions in rats: the involvement of the oxidative capacity and arginine metabolism

Abstract Carbon tetrachloride (CCl4) represents an organic chemical that causes reactive oxygen species derived organ disturbances including male infertility. Melatonin (MLT) is a neurohormone with strong antioxidant capacity, involved in numerous physiological processes. In this study we evaluated the capability of MLT, administered in a single dose of 50 mg/kg, to preserve the testicular tissue function after an acute administration of CCl4 to rats. The disturbance in testicular tissue and the effects of MLT after CCl4 exposure were estimated using biochemical parameters that enabled us to determine the tissue (anti)oxidant status and the intensity of arginine/nitric oxide metabolism. Also, the serum levels of testosterone and the histopathological analysis of tissue gave us a better insight into the occurring changes. A significant diminution in tissue antioxidant defences, arginase activity and serum testosterone levels, followed by the increased production of nitric oxide and extensive lipid and protein oxidative damage, was observed in the CCl4-treated group. The application of MLT after the CCl4 caused changes, clearly visible at both biochemical and histological level, which could be interpreted mainly as a consequence of general antioxidant system stimulation and a radical scavenger. On the other hand, the application of MLT exerted a limited action on the nitric oxide signalling pathway.

Metabonomics Analysis of Sailuotong Capsules in Treatment of Acute Cerebral Ischemia in Rats / 中国实验方剂学杂志

Objective:To explore the mechanism of Sailuotong capsules in treating acute cerebral ischemia from the perspective of metabonomics. Method:A total of 24 SD rats were randomly divided into 3 groups, including sham-operated group, model group and Sailuotong group (33 mg·kg-1). The rat model of acute multiple cerebral infarction was established by injecting fluorescent microspheres into internal carotid artery. After the successful operation, rats in Sailuotong group were administered by duodenal injection immediately, and the dosage volume was 2 mL·kg-1. Endogenous metabolites in rat brain tissues of each group were determined by UPLC-Q-TOF-MS. The relevant data and biomarkers were analyzed by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). Result:The analysis of pattern recognition indicated that the metabolite profiles in model group and sham-operated group were separated obviously, and ten biomarkers related to acute cerebral ischemia were also identified. Compared with the sham-operated group, contents of N-acetylaspartate (NAA), fumaric acid, glutathione, dehydroascorbic acid, aspartic acid and S-adenosylhomocysteine were decreased, while the contents of arginine, citrulline, saccharopine and hydantoin-5-propionic acid were increased in the model group. Meanwhile, the ten abnormal biomarkers mentioned above got restoration in Sailuotong group. Conclusion:The main regulated metabolic pathways of Sailuotong capsules are NAA metabolism, arginine metabolism, energy metabolism, oxidative stress, etc.