This study investigates the effects of metoprolol (METO) or/and pravastatin (PRAV) on the pharmacokinetics of metformin (METF) in rats. Twenty-eight male SD rats were divided into METF group, METF+METO group, METF+PRAV group and METF+METO+PRAV group. Blood samples were collected at 10, 20, 40, 60, 90, 120, 180, 240, 360, 480 and 600 min after oral administration of metformin, and concentration of metformin in plasma was determined by HPLC. Compared to the METF group, C_max of metformin was significantly decreased (P < 0.01) and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO group; t_1/2 was significantly decreased in the METF+PRAV group; C_max was significantly decreased and MRT_0-t was significantly increased in the METF+METO+PRAV group. Compared to the METF+METO group, MRT_0-t of metformin was significantly decreased in the METF+METO+PRAV group. Compared to the METF+PRAV group, C_max of metformin was significantly decreased (P < 0.01), and MRT_0-t, t_1/2 and V were significantly increased in the METF+METO+PRAV group. There exist multiple drug interactions of metformin, metoprolol and pravastatin in rats.

The binding of rhaponticin to bovine serum albumin (BSA)-bovine lactoferrin (BLF) and the factors that affect BSA-BLF interaction have been studied by fluorescence spectroscopy and Fourier transform infrared spectroscopy. In the fluorescence experiment, RT quenched the fluorescence intensity of mixed proteome and the maximum emission wavelength of BSA, BLF and BSA-BLF proteins system. RT caused obvious red-shift fluorescence for an interaction between RT and proteome. The interaction between RT and proteome was impacted by single-component protein molecular interactions and the interaction between RT-BSA and RT-BLF, the microenvironment of solutions were the factors impacting the interactions between RT and proteome, which impacted quantitative expression of the general environment micro environmental factors. In the Fourier transform infrared spectroscopy, the secondary conformation of protein molecules of single component in the protein group were changed, and the difference of the molecules' structure was responsible for the differences in the molecular conformation changes. The molecules' interaction in the single-component protein affected secondary conformation of the proteins' molecule. The proteins' concentration ratio and the interaction were different in degree of molecular conformational change. These data demonstrates an example of combination of fluorescence spectrum experiment with Fourier transform infrared spectroscopy in the study of protein structura.

This study was designed to reverse multidrug resistance of lung cancer cells by downregulating MDR1 genes through RNA interference (RNAi) technology. A novel biodegradable cationic polymer (PEG-b-PLG-g-PEIs, GGI) was synthesized and characterized by ¹H NMR. The particle size and zeta potential were measured by dynamic light scattering (DLS). The cell viability profile of GGI was tested by MTT method with both A549 and A549/DDP cell lines. Flow cytometry (FCM) technology was used to investigate the efficiency and intensity of delivering siRNA to cells by GGI polymer. RT-PCR and Western blot were used to detect the mRNA and P-gp expression after GGI/MDR1 siRNA transfection assay. The sensitivity of cisplatin administration after transfecting GGI/MDR1 siRNA polyplexs was performed with MTT and Annexin V-FITC/PI methods. The results suggest that the particle size and zeta potential of GGI/siRNA were 150-200 nm and 16-28 mV. GGI exhibited a lower cell cytotoxity than PEI 25K and higher efficiency of delivering siRNA, which dramatically decreased the expression of MDR1 mRNA and P-gp of A549/DDP cells and increased much sensitivity to cisplatin in A549/DDP cells. GGI holds a great potential in gene delivery as a novel cationic polymer for further investigation.

Research of plant development and metabolism has drawn lots of attention with the fast development of science of mycorrhizal biology, molecular biology and metabonomics technology. It has become one of hot fields in the study of endophytes and plant, which would affect plant's metabolite composition. This would provide opportunity for appraising and modifying traits to medicinal plant, and would also perfect the tranditional standpoint on forming reason of medicinal plant genuineness. Here we provide a review of theory and mechanism, research and application of interaction between plant and endophyte. This review may enhance understanding of medicinal plant, and evaluating the quality of herbs in production.

Bile acids play critical roles in the regulation of metabolism and absorption of lipids. The ileal apical sodium-dependent bile acid transporter (ASBT) located at the enterocyte brush border is responsible for the reuptake of bile acids and the maintenance of bile acid homeostasis. Recently, a number of investigations have been made concerning the regulation and control of ASBT and the relationship between ASBT and intestinal inflammation, tumorigenesis, diabetes mellitus and hyperlipemia, which suggests ASBT as a potential therapeutic target of these diseases. In this review, advances in the study of above-mentioned issues were summarized.

This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance (¹H NMR) metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

Property and flavor theory of traditional Chinese medicine (TCM) is the core base for clinical treatment of diseases. However, few research about its chemical and biological characterization was performed. In this paper, network pharmacology was adopted to review patterns around the theory of TCM. "Xiaoke" prescription database, which combinations of herb medicines for diabetes therapy, was firstly built to explore prescription regularity and screen core paired-components. The prescription regularity and molecular mechanism of flavor composition were explored through the relationship of "drug-compound-target-pathway-function" by ChEMBL, CTD and KEGG datebase. As a result, the tastes of "Gan" (sweetish taste) and "Ku" (bitter taste) were the popular therapeutic flavor to regulate the disorder of glucose and lipid metabolisms. The mechanism of Xiaoke was summarized from representative traditional Chinese medicine partner "Zhimu-Huangbai" and "Huangqi-Gegen". The key components of "Gan", including saponins stimulated insulin secretion, improve insulin resistance and promote glucose utilization. The components of "Ku", including flavonoids and alkaloids regulate inflammatory cytokines, promoted the utilization of glucose, improve endocrine and metabolism through MAPK, PI3K-Akt, PPAR signal pathway. The TCM therapeutic mechanism about "Xiaoke" was preliminarily summarized to clear "heat" by anti-inflammation and immunoregulation, to regulate glucolipid metabolism for removing the satiation of digestion, and to improve the utilization of insulin and diabetes complications for endocrine adjusting. The results demonstrate that therapeutic principle of TCM for "Xiaoke" is comprehensive via multi pathway. This study provides a new research method and strategy for exploring the mechanism of TCM for diabetes therapy.

Abelmoschus manihot (L.) Medic., a folk herbal medicine in China, is a flowering plant belonging to Abelmoschus L. genus and Malvaceae family, which has been reported with an antidepressant activity. The study was designed to isolate flavonoids from Abelmoschus manihot corolla and explore the action mechanism of antidepressant activities. The flavonoids were isolated and purified by D101 macroporous resin column, polyamide column and Sephadex LH-20 sequentially and identified as myricetin-3-O-β-D-glucoside (1), gossypetin-8-O-β-D-glucuronide (2, G-8-G), gossypetin-3'-O-β-D-glucoside (3), quercetin-3'-glucoside (4, Q-3-G), isoquercitrin (5, IQT), hyperoside (6, HY), myricetin (7), quercetin (8, QT). Compounds 2, 4, 5, 6 and 8 (15, 30 and 60 mg·kg^-1) were orally administered to mice and the reaction was observed in tail suspension test (TST) and forced swimming test (FST). Western blot analysis was used in determination of the protein expressions of brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB) and phosphorylation eukaryotic elongation factor 2 (p-eEF2). The results revealed that only Q-3-G and G-8-G (15, 30, 60 mg·kg^-1) significantly reduced the immobility time in FST and TST. Furthermore, Q-3-G and G-8-G remarkably increased the expression of BDNF and TrkB, and decreased the expression of p-eEF2. These results suggest that Q-3-G and G-8-G had an obvious antidepressant activity via up-regulation of BDNF expression. The new observation will provide a new direction in the development of antidepressant in the treatment of major depressive disorder (MDD).

Excessive reactive oxygen species (ROS) is associated with an array of pathological conditions, including cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. However, ROS-responsive materials have drawn attention in the development of drug delivery systems. There are many types of ROS-responsive materials explored in drug delivery applications, including sulfur-based responsive polymers, selenium-based responsive polymers, tellurium-based responsive polymers, oxalate ester-containing polymers, phenylboronic ester-containing polymers and unsaturated lipids. When integrated with ROS-responsive drug delivery systems, a photosensitizer is used as a light-sensitive element to generate ROS, mainly singlet oxygen (¹O₂), which in turn activates the ROS-triggered drug delivery.

Postoperative intra-abdominal adhesion is one of the most common complications in the postoperative period. Current remedies are very ineffective to prevent the pathological outcomes except steroid hormones. Rhynchophylline is deemed as a pharmacologically active component from traditional Oriental medicine Uncaria rhynchophylla (Miq.) Jacks. (Rubiaceae). This study was designed to investigate the preventative effect of rhynchophylline on the abdominal adhesions in rats. Rhynchophylline relieved the experimental abdominal adhesion and decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the blood serum in a dose-dependent manner. The levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were reduced significantly in the peritoneal fluid. The potential mechanism of the activity is related to inhibition of the TGF-β1/Smad signaling pathway.