ABSTRACT. The effect of sinomenine (SIN) on the toll-like receptor (TLR) signal transduction pathway as well as the expression of myeloid differentiation factor 88 (MyD88) and tumor necrosis factor (TNF) receptorassociated factor-6 (TRAF6) was investigated. SIN inhibition of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) proliferation and RA cartilage and subchondral bone destruction was also investigated. RA-FLS were cultured in vitro and the intracellular alkaline phosphatase (ALP) activity was determined in order to obtain the optimal drug concentration. The rate of cell proliferation was determined. Fluorescence quantitative polymerase chain reaction (PCR) was applied to determine the MyD88 and TRAF-6 gene expression and western blot was used to detect the MyD88 and TRAF-6 protein expression. The ALP activity in the SIN groups was lower than that in the control group, among which the 0.5 mM SIN group had the lowest ALP activity (P < 0.01). The rate of RA-FLS proliferation detected by CCK-8 assay in the 0.5-mM SIN group was lower than that in 18929 Effect of sinomenine on MyD88 and TRAF6 expression ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 18928-18935 (2015) the control group (P < 0.01) and was the highest 4 days after SIN induction. Gene and protein expression of MyD88 and TRAF-6 were downregulated significantly in the 0.5-mM SIN group compared to that in the control group (P < 0.01). SIN effectively inhibited MyD88 and TRAF-6 expression in RA-FLS, which may be one of the important molecular mechanisms involved in RA treatment and prevention of cartilage and subchondral bone destruction.

Background: Non-alcoholic fatty liver is one of the most common comorbidities of diabetes. It can cause disturbance of glucose and lipid metabolism in the body, gradually develop into liver fibrosis, and even cause liver cirrhosis. Mangiferin has a variety of pharmacological activities, especially for the improvement of glycolipid metabolism and liver injury. However, its poor oral absorption and low bioavailability limit its further clinical development and application. The modification of mangiferin derivatives is the current research hotspot to solve this problem. Methods: The plasma pharmacokinetic of mangiferin calcium salt (MCS) and mangiferin were monitored by HPLC. The urine metabolomics of MCS were conducted by UPLC-Q-TOF-MS. Results: The pharmacokinetic parameters of MCS have been varied, and the oral absorption effect of MCS was better than mangiferin. Also MCS had a good therapeutic effect on type 2 diabetes and NAFLD rats by regulating glucose and lipid metabolism. Sixteen potential biomarkers had been identified based on metabolomics which were related to the corresponding pathways including Pantothenate and CoA biosynthesis, fatty acid biosynthesis, citric acid cycle, arginine biosynthesis, tryptophan metabolism, etc. Conclusions: The present study validated the favorable pharmacokinetic profiles of MCS and the biochemical mechanisms of MCS in treating type 2 diabetes and NAFLD.

The flavonoid compound scutellarin (Scu) is a traditional Chinese medicine used to treat a variety of diseases; however, the use of scutellarein (Scue), the hydrolysate of Scu, and its mechanisms of action in Alzheimer's disease (AD) have not been fully elucidated. In the present study, the effects of Scue on amyloid β (Aβ)-induced AD-like pathology were investigated. An in vitro model of inflammation and an aged rat model were used to confirm the effects of Scue. In vitro MTT assays and flow cytometry were used to assess the effects of Scue on cell viability and apoptosis, respectively. A Morris water maze was used to evaluate spatial learning and memory, and the levels of Aβ deposition, superoxide dismutase, malondialdehyde, apoptosis, neuro-inflammatory factors and nuclear factor-κB (NF-κB) activation in hippocampal tissues in vivo were measured to determine the effect of Scue in AD. Scue may be protective, as it decreased the apoptosis of hippocampal cells in vitro , inhibited Aβ-induced cognitive impairment, suppressed hippocampal neuro-inflammation and suppressed activation of NF-κB in vivo . Therefore, Scue may be a useful agent for the treatment of Aβ-associated pathology in the central nervous system through inhibition of the protein kinase B/NF-κB signaling pathway and thus, future studies are required to investigate the efficacy of Scue in patients with AD.

Ginsenosides, as the most important constituents of ginseng, have been extensively investigated in cancer chemoprevention and therapeutics. Among the ginsenosides, Compound K (CK), a rare protopanaxadiol type of ginsenoside, has been most broadly used for cancer treatment due to its high anticancer bioactivity. However, the functional mechanism of CK in cancer is not well known. This review describes the structure, transformation and pharmacological activity of CK and discusses the functional mechanisms of CK and its metabolites, which regulate signaling pathways related to tumor growth and metastasis. CK inhibits tumor growth by inducing tumor apoptosis and tumor cell differentiation, regulates the tumor microenvironment by suppressing tumor angiogenesis-related proteins, and downregulates the roles of immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs). There is currently much research on the potential development of CK as a new strategy when administered alone or in combination with other compounds.

To better understand the antipyretic mechanism of Baihu decoction, the network pharmacology was used to predict its antipyretic components, targets, functions and pathways, and the prediction results were experimentally verified. BATMAN-TCM was used to obtain the components of Baihu decoction, GeneCards was used to screen fever related targets, STRING was used to analyze the protein interaction network of the selected targets. Bioconductor software was used to analyze the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway, and one of the KEGG pathway analyses was performed by cell inflammation model, and was verified by experiments. In the results, total 263 compounds were screened out, 54 potential antipyretic targets were identified, 84 items were obtained by GO function analysis, and 29 pathways were obtained by KEGG analysis, including hypoxia inducible factor-1, Forkhead box O (FOXO) Ras related protein 1 (Rap1), nuclear factor-κ (NF-κB) and other signalling pathways. In the verification experiment of NF-κB signalling pathway, the expression of NF-κB, Inhibitory kappa B kinase beta (IκKβ) and IκBα protein were significantly difference between the Baihu decoction group (P < 0.01) and the model group (P < 0.05), suggesting that Baihu decoction plays the antipyretic effect by affecting IκKβ, Inhibitory kappa B alpha (IκBα) and NF-κB. In conclusion, the interaction of multiple targets in the antipyretic effect of Baihu Decoction and its biological function and pathways were preliminarily demonstrated.