The Mechanism Underlying the Hypoglycemic Effect of Epimedin C on Mice with Type 2 Diabetes Mellitus Based on Proteomic Analysis.

Type 2 diabetes mellitus (T2DM) has become a worldwide public health problem. Epimedin C is considered one of the most important flavonoids in Epimedium, a famous edible herb in China and Southeast Asia that is traditionally used in herbal medicine to treat diabetes. In the present study, the therapeutic potential of epimedin C against T2DM was ascertained using a mouse model, and the mechanism underlying the hypoglycemic activity of epimedin C was explored using a label-free proteomic technique for the first time. Levels of fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and oral glucose tolerance, as well as contents of malondialdehyde (MDA) and low-density lipoprotein cholesterol (LDL-C) in the 30 mg·kg-1 epimedin C group (EC30 group), were significantly lower than those in the model control group (MC group) (p < 0.05), while the contents of hepatic glycogen, insulin, and high-density lipoprotein cholesterol (HDL-C), as well as activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the EC30 group were notably higher than those in the MC group (p < 0.05). The structures of liver cells and tissues were greatly destroyed in the MC group, whereas the structures of cells and tissues were basically complete in the EC30 group, which were similar to those in the normal control group (NC group). A total of 92 differentially expressed proteins (DEPs) were enriched in the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In the EC30 vs. MC groups, the expression level of cytosolic phosphoenolpyruvate carboxykinase (Pck1) was down-regulated, while the expression levels of group XIIB secretory phospholipase A2-like protein (Pla2g12b), apolipoprotein B-100 (Apob), and cytochrome P450 4A14 (Cyp4a14) were up-regulated. According to the KEGG pathway assay, Pck1 participated in the gluconeogenesis and insulin signaling pathways, and Pla2g12b, Apob, and Cyp4a14 were the key proteins in the fat digestion and fatty acid degradation pathways. Pck1, Pla2g12b, Apob, and Cyp4a14 seemed to play important roles in the prevention and treatment of T2DM. In summary, epimedin C inhibited Pck1 expression to maintain FBG at a relatively stable level, promoted Pla2g12b, Apob, and Cyp4a14 expressions to alleviate liver lipotoxicity, and protected liver tissues and cells from oxidant stress possibly by its phenolic hydroxyl groups.

Proteomic Analysis of Protective Effects of Epimedium Flavonoids against Ethanol-Induced Toxicity in Retinoic Acid-Treated SH-SY5Y Cells.

Alcohol (ethanol) is one of the most common addictive psychoactive substances in the world, and alcoholism may result in harmful effects on human health, especially on the nervous system. Flavonoids are regarded as the main active constituent in Epimedium, which has been used to cure some nervous system diseases such as amnesia for over 1000 years. Here, the protective effects of Epimedium flavonoids against ethanol-induced toxicity in retinoic acid (RA)-treated SH-SY5Y cells were investigated. Their mechanism was explored by a label-free proteomic approach combined with bioinformatic analysis for the first time. The results showed that ethanol treatment decreased cell viability by 18%, whereas the viability increased significantly after intervention with Epimedium flavonoids (p < 0.01). According to proteomic and bioinformatic analyses, hundreds of differentially expressed proteins (DEPs) were identified and classified as biological process (GO_BP), cellular component (GO_CC) and molecular function (GO_MF). Among them, GO_MF of DEPs, especially molecular function relevant to G proteins, greatly changed in SH-SY5Y cells pretreated by Epimedium flavonoids. In the alcoholism pathway, the expression of the Gi protein was up-regulated under the influence of ethanol, whereas Epimedium flavonoids could reverse the expression profile, both of which were validated by Western blot assay. In conclusion, Gi protein seemed to be an important factor in the alcoholism pathway to suppress the ethanol-induced toxicity of SH-SY5Y cells. These findings suggest a protective potential of Epimedium flavonoids against ethanol-induced toxicity to neurons via the regulation of Gi protein function.

Flavonoids from Epimedium pubescens: extraction and mechanism, antioxidant capacity and effects on CAT and GSH-Px of Drosophila melanogaster.

BACKGROUND: Epimedium is a famous medicinal plant in China, Southeast Asian and some other regions. Flavonoids are regarded as its supremely important active constituents used in phytomedicines and/or functional foods. It is of theoretical and applied significance to optimize the procedure for extraction of flavonoids with high bioactivity from Epimedium, to unveil extraction mechanism, to identify chemical composition of flavonoids, to analyze free radical-scavenging ability of flavonoids, and to investigate their effects on the model organism Drosophila melanogaster. METHODS: Box-Behnken design was applied to optimization of extraction procedure. Laser diffraction particle size analysis was used to clarify extraction mechanism. Chemical composition of flavonoids was analyzed using high-performance liquid chromatography. Antiradical capacities of flavonoids were determined by chemical-based assay. Then, effects of flavonoids on catalase (CAT) and glutathione peroxidase (GSH-Px) in D. melanogaster were investigated for the first time. RESULTS: The optimal condition for ultrasonic extraction of antioxidant flavonoids from Epimedium pubescens was achieved and extraction mechanism was discussed. Epimedium flavonoids contained icariin, epimedin A, epimedin B and epimedin C. Epimedium flavonoids exhibited the ability to scavenge ABTS+ and DPPH⋅ radicals with EC50 values of 55.8 and 52.1 µg/ml, respectively. Moreover, Epimedium flavonoids were able to increase activities of CAT and GSH-Px in D. melanogaster. For females, oral administration of flavonoids improved CAT and GSH-Px activities by 13.58% and 5.18%, respectively. For males, oral administration of flavonoids increased CAT and GSH-Px activities by 13.90% and 5.65%, respectively. CONCLUSION: Flavonoids ultrasonically extracted from E. pubescens considerably affected antioxidant defense system in D. melanogaster. Flavonoids of E. pubescens showed great potential for becoming a natural antioxidant because of their antiradical ability and effects on CAT and GSH-Px of the model organism.

The effect of tripterygium glucoside tablet on pharmacokinetics of losartan and its metabolite EXP3174 in rats.

Losartan and tripterygium glucoside tablet (TGT) are often simultaneously used for reducing urine protein excretion in clinic. However, it is unknown whether there is potential herb-drug interaction between losartan and TGT. The aim of this study was to investigate their potential herb-drug interaction, and clarify the mechanism of the effect of TGT on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. The plasma concentrations of losartan and EXP3174 were determined by LC-MS, and the main pharmacokinetic parameters were calculated. The Cmax , t1/2 and AUC(0-t) of losartan became larger after co-administration, while the Cmax and AUC(0-t) of EXP3174 became smaller, suggesting that TGT could influence the pharmacokinetics of losartan and EXP3174. The effects of TGT and its main components on the metabolic rate of losartan were further investigated in rat liver microsomes. Results indicated that TGT and its two main ingredients could decrease the metabolic rate of losartan. Therefore, it was speculated that TGT might increase the plasma concentration of losartan and decrease the concentration of EXP3174 by inhibiting the metabolism of losartan. The results could provide references for clinical medication guidance of losartan and TGT to avoid the occurrence of adverse reactions.

miRNAs: biogenesis, origin and evolution, functions on virus-host interaction.

MicroRNAs (miRNAs) are small endogenous non-coding functional RNAs. They can play vital roles in post-transcriptional regulating mRNAs transcripts in nearly all biological processes. More and more reports on miRNAs come from different species (animal, plant, bacteria, virus) in the researches in development, immunity, apoptosis, tumor, virus-host interaction. These recent findings provide new insights into the roles of miRNAs as well as their function. This review outlines the ever-deepening understanding of miRNAs (biogenesis, origin, evolution), and discusses functions from host and viral miRNAs in the context of virus-host interaction.