Investigation of the therapy targets of Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu recipe on type 2 diabetes by serum proteome labeled with iTRAQ.

ETHNOPHARMACOLOGY RELEVANCE: Based on basic theories of Chinese medicine, Yi-Qi-Yang-Yin-Hua-Tan-Qu-Yu (YQYYHTQY) recipe was constituted by eleven kinds of Chinese herbs and effective in treatment of type 2 diabetes (T2DM). But the therapy target was unclear. OBJECTIVE: In this study, we used the serum proteome labeled by iTRAQ to find therapy target of YQYYHTQY recipe on T2DM. MATERIALS AND METHODS: The rat model was induced by high-fat diet (HFD) and streptozotocin (STZ, 30 mg/kg). Drugs were administered to rats once daily for 14 days. Related laboratory parameters were observed. Serum proteome were compared between T2DM and YQYYHTQY group using the iTRAQ labeling quantitative proteomics technique. Functional differential proteins were analysis by STRING software. Target proteins were confirmed by ELISA kits. RESULTS: Hyperglycemia, hyperinsulinemia, insulin resistance, decrease of glucose transporter, depilation, less activity, flock together, depression, ecchymosis of tongue and tail appearance, the typical diabetic patients "a little more than three" symptoms, as well as the decrease of grip strength, serum cyclic adenosine monophosphate (cAMP)/ cyclic guanosine monophosphate (cGMP) ratio, serum high density lipoprotein-cholesterol (HDL-C) and the increase of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), thromboxane B2 (TXB2)/ 6-keto prostaglandin F1α (6-keto PGF1α) ratio, endothelin-1 (ET-1) levels were found in T2DM group. After drugs treatment, all the above indexes almost were improved in different degrees and effect of YQYYHTQY recipe was superior to pioglitazone hydrochloride. In addition, there were 23 differential proteins, 5 up-regulated and 18 down-regulated proteins. Of them, there were 4 proteins related with diabetes, blood and behavior. Cell division control protein 42 homolog (CDC42) and Ras homolog gene family member A (RhoA) were the therapy targets of YQYYHTQY recipe on T2DM. CONCLUSIONS: YQYYHTQY recipe showed therapy effect on T2DM. CDC42 and RhoA proteins were the therapy targets of YQYYHTQY recipe.

Crystal structure of N-(7-di-bromo-methyl-5-methyl-1,8-naphthyridin-2-yl)benzamide-pyrrolidine-2,5-dione (1/1).

The title compound, C17H13Br2N3O·C4H5NO2, is a co-crystal of N-(7-di-bromo-methyl-5-methyl-1,8-naphthyridin-2-yl)benzamide and pyrrolidine-2,5-dione (succinimide). The benzamide mol-ecule exhibits pseudo-mirror symmetry, with an r.m.s. deviation of the non-H atoms of 0.09 Š(except for the two Br atoms). The angle between the least-squares planes of the two mol-ecules is 26.2 (2)°. In the crystal, the two mol-ecules are mutually linked by N-H⋯O and N-H⋯N hydrogen bonds. The packing is consolidated by C-H⋯(O,N) hydrogen bonds and π-π stacking inter-actions.

Crystal structure of 9-(di-bromo-meth-yl)-1,1-di-fluoro-3,7-dimethyl-1H-[1,3,5,2]oxadi-aza-borinino[3,4-a][1,8]naphthyridin-11-ium-1-uide.

The mol-ecule of the title 1,8-naphthyridine-BF2 derivative, C12H10BBr2F2N3O, is located on a mirror plane running parallel to the entire ring system and the attached methyl C atoms. Individual mol-ecules are stacked along the b-axis direction. The cohesion in the crystal structure is accomplished by C-H⋯F hydrogen bonds and additional off-set π-π inter-actions [centroid-to-centroid distance = 3.6392 (9) Å, slippage 0.472 Å], leading to the formation of a three-dimensional supra-molecular network.

[Changes of HPAA in Different Rat Models of Gan Stagnation, Pi Deficiency, Gan Stagnation Pi Defi- ciency and Interventional Effect of Chaishu Sijun Decoction].

OBJECTIVE: To compare changes of hypothalamus-pituitary-adrenal axis (HPAA) in different rat models of Gan stagnation (GS), Pi deficiency (PD), Gan stagnation Pi deficiency (GSPD) syndromes, and to observe interventional effect of Chaishu Sijun Decoction (CSD, capable of soothing Gan-qi invigorating Pi) on them. METHODS: Seventy Wistar rats were divided into the normal control group (group 1), the GS group (group 2), the PD group (group 3), the GSPD group (group 4), the GS intervention group (group 5), the PD intervention group (group 6), and the GSPD intervention group (group 7) according to random digit table, 10 in each group. Rats in group 1 received no treatment. Rats in group 2 and 5 were modeled by chronic restraint method. Rats in group 3 and 6 were modeled by excess fatigue plus alimentary abstinence method. Rats in group 4 and 7 were modeled by chronic restraint, excess fatigue, and alimentary abstinence method. At the 2nd weekend of modeling, CSD at 2.86 g/kg was fed to rats in group 5, 6, and 7 by gastrogavage for 2 successive weeks. Equal volume of distilled water was given to rats in the rest 4 groups. On the 29th day, rats were killed, adrenal weight weighed, and adrenal index calculated. Levels of plasma and hypothalamus corticotropin-releasing hormone (CRH), plasma and pituitary adrenocorticotrophic hormone (ACTH), and plasma corticosterone (CORT) were determined using radioimmunity. RESULTS: Compared with group 1, adrenal index significantly decreased in group 2, 3, and 4 (P < 0.05). Of them, plasma and hypothalamus CRH, plasma CORT increased significantly in group 2 and 4 (P < 0.05). Besides, plasma and pituitary ACTH increased in group 4 (P < 0.05). Plasma and pituitary ACTH, as well as plasma CORT decreased significantly in group 3 (P < 0.05). Compared with group 2, 3, and 4, adrenal index increased significantly in group 5, 6, and 7 (P < 0.05). Compared with group 2, plasma CORT, hypothalamus CRH, and pituitary ACTH decreased significantly in group 5 (P < 0.05). Compared with group 3, plasma ACTH and CORT increased significantly in group 6 (P < 0.05). Compared with group 4, plasma CRH, ACTH, CORT, hypothalamus CRH, and pituitary ACTH decreased in group 7 (P < 0.05). CONCLUSIONS: The function of HPA .axis was damaged to varying degrees in rats of the three models in this experiment. Hyperactivity of HPA axis existed in GS syndrome and GSPD syndrome. Impairment of feedback regulation in hypothalamus and pituitary was accompanied in GSPD syndrome. Hypofunction of HPA axis existed in PDS. CSD, capable of soothing Gan-qi invigorating'Pi, showed improvement on disarranged HPAA, but with optimal effect on GSPD syndrome. CSD had higher correlation with GSPD syndrome.

[Effect of chaishu sijun decoction on the gonad axis of gan-qi stagnation, Pi deficiency, and gan-qi stagnation pi deficiency model rats].

OBJECTIVE: To observe changes of gonad functions of Gan-qi stagnation (GS), Pi deficiency (PD), Gan-qi stagnation Pi deficiency (GSPD) model rats, and the effect of Chaishu Sijun Decoction (CSD) on them. METHODS: Rats were randomly divided into 7 groups according to romdom digit table, i.e., the normal control group, the GS model group, the GS medication group, the PD model group, the PD medication group, the GSPD model group,and the GSPD medication group, 10 in each group. Rats in the GS model group, the PD model group, and the GSPD model group were treated with chronic restraint, improper diet +excessive fatigue, chronic restraint +improper diet +excessive fatigue. The model was established for 4 successive weeks. Starting from the 15th day of modeling, CSD at the daily dose of 3.57 g/kg was given by gastrogavage to them for 14 successive days. Equal volume of distilled water was given by gastrogavage to rats in each model group and the normal control group for 14 successive days. The blood contents of gonadotrophin releasing hormone (GnRH), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and testosterone (T) were detected in rats of each group. RESULTS: Compared with the normal control group, there was statistical difference in GnRH, T, E,, and FSH in the GS, PD, and GSPD model groups (P < 0.05, P < 0.01). The content of LH was elevated in the GS model group (P < 0.05) and declined in the GSPD model group (P < 0.01). Compared with the GS model group, the contents of FSH, LH, and T decreased and E2 increased in the PD model group (all P < 0.05); the contents of FSH and LH also declined in the GSPD model group (P < 0.05). Compared with the PD model group, the T content increased and FSH decreased in the GSPD model group (all P < 0.05). Compared with each corresponding model group, the FSH content decreased (P < 0.01) and LH increased in the GS medication group; the T content increased, E2 and LH decreased (P < 0.05, P < 0.01) in the PD medication group; the T content decreased (P < 0.01), GnRH, E2, FSH, and LH increased (P < 0. 05, P < 0.01) in the GSPD medication group. CONCLUSIONS: There exist different degrees of abnormal function of the gonad axis in the GS, PD, and GSPD models. CSD had certain regulatory effect on the 3 syndromes. Of them, it showed a more comprehensive role in improving the gonad function axis. Results of this experiment had provided the experimental evidence for higher correlation between CSD and GSPD syndrome.