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2-Substituted-3-sulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides have been proposed as novel structures of PI3K inhibitors and anticancer agents based on bioisostere. In the present study, 2-substituted-3-sulfonamino-5-(4-morpholinoquinazolin-6-yl)benzamides and 2-methoxy-3-sulfonamino-5-(4-morpholinoquinolin-6-yl)benzamides were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against four human cancer cell lines, including A549, HCT-116, U-87 MG and KB. The SAR of the title compounds was preliminarily discussed. Compound 1a with potent antiproliferative activity was tested for its inhibitory activity against PI3K and mTOR and its effect on the AKT and p-AKT 473 . The anticancer effect of 1a was evaluated in established nude mice U-87 MG xenograft model. The results suggest that compound 1a can significantly inhibit PI3K/AKT/mTOR pathway and tumor growth. These findings strongly support the assumption that title compounds are potent PI3K inhibitors and anticancer agents.

A series of [1,2,4]triazolo[1,5-a]pyridinylpyridines were synthesized and characterized. Their antiproliferative activities in vitro were evaluated by MTT against three human cancer cell lines including HCT-116, U-87 MG and MCF-7 cell lines. The SAR of target compounds was preliminarily discussed. The compounds 1c and 2d with potent antiproliferative activities were tested for their effects on the AKT and p-AKT 473 . The anticancer effect of 1c was evaluated in mice bearing sarcoma S-180 model. The results suggest that the title compounds are potent anticancer agents.

Chinese herbal medicines possess the therapeutic potential for mood disorders. This double-blind, randomized, placebo-controlled study was designed to evaluate the efficacy and side effects of the herbal medicine called Free and Easy Wanderer Plus (FEWP) as an adjunct to carbamazepine (CBZ) in patients with bipolar disorders. One hundred and twenty-four bipolar depressed and 111 manic patients were randomized to treatment with CBZ alone, CBZ plus FEWP, or equivalent placebo for 12 weeks. CBZ was initiated at 300mg/day and FEWP was given at a fixed dose of 36g/day. Efficacy measures included the Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale , Young Mania Rating Scale, Bech-Rafaelsen Mania Scale, and Clinical Global Impression-Severity (CGI-S). CBZ monotherapy produced significantly greater improvement on manic measures at week 2 through endpoint and CGI-S of depression at endpoint compared to placebo. CBZ monotherapy also yielded significantly higher clinical response rates than placebo on bipolar depression (63.8% vs. 34.8%, p=0.044) and mania (87.8% vs. 57.1%, p=0.012). Compared to CBZ monotherapy, adjunctive FEWP with CBZ resulted in significantly better outcomes on the three measures of depression at week 4 and week 8 and significantly greater clinical response rate in depressed subjects (84.8% vs. 63.8%, p=0.032), but failed to produce significantly greater improvement on manic measures and the response rate in manic subjects. There was a lesser incidence of dizziness and fatigue in the combination therapy compared to CBZ monotherapy. These results suggest that adjunctive FEWP has additive beneficial effects in bipolar patients, particularly for those in depressive phase.

Effective components, ligustilide and butylidenephthalide, from Ligusticum Chuanxiong (Ligusticum wallichii Franchat, Umbelliferae) were screened and identified by using a cell membrane chromatography (CMC) and a gas chromatography/mass spectrometry (GC/MS). The components showed the effects of inhibiting vasoconstriction in vitro on rat abdominal aorta segments. The screening procedure was performed in a rat artery CMC column (50 mm x 2.0 mm I.D.) with a sodium phosphate buffer (pH 7.4) as mobile phase at 37 degrees C. The identification was accomplished by a DB-5MS 30 m capillary column (0.25 mm I.D., 0.25 microm film thickness) with helium as carrier gas operating under program control temperature and electron impact ionization mass spectrometer in a scan mode. Results demonstrated that ligustilide and butylidenephthalide can act on rat artery cell membrane similar to verapamil in CMC system. They significantly inhibited the vasoconstrictions induced by norepinephrine bitartrate (NE) and calcium chloride (CaCl2). The relaxing effect of ligustilide on the NE- and CaCl2-induced constrictions is more potent than that of butylidenephthalide. Ligustilide and butylidenephthalide seem to be the two main effective components of Ligusticum Chuanxiong as a traditional Chinese medicine for treating blood vessel diseases.

Excess aluminum (Al) exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential link between chronic Al exposure and Alzheimer's disease. In the present study, we sought to evaluate the protective effects of the herbal medicine Dipsacus asper extract against the cognitive impairment and overexpression of hippocampal beta-amyloid protein (Abeta) induced by chronic Al exposure in rats. Vitamin E (VE) was used as a positive control. Following exposure to 0.3% aluminum chloride (AlCl(3)) solution for 90 days in their drinking water, animals displayed a striking decrease (>80%) in step-through latency in the passive avoidance task and a significant increase (123%) in the number of Abeta immunoreactive cells in the hippocampus compared to controls. Al-exposed animals were then randomly assigned to receive vehicle, Dipsacus asper extract (4 g/kg), or VE (40 mg/kg) treatment up to 5 months. Both Dipsacus asper extract and VE significantly ameliorated animal's performance impairment in the passive avoidance task and suppressed the overexpression of hippocampal Abeta immunoreactivity. The effects of Dipsacus asper extract, but not VE, increased with time of treatment. The present results suggest that Dipsacus asper extract may possess therapeutic effects against Alzheimer's disease.

To study the supermolecular interaction between different concentrations of hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and imperatorin (IM) and isoimperatorin (ISO) using phase solubility analysis.Different concentrations of hydroxypropyl-beta-cyclodextrin were prepared, added overdose of imperatorin or isoimperatorin, made a phase solubility diagram.The relationship of phase solubility was approximatively linear and the model of inclusion compound was AL and the inclusion ratio of IM, ISO versus HP-beta-CD was 1: 1. The inclusion constants were 214.4, 587.2 L/mol respectively.Supermolecular inclusion of HP-beta-CD of imperatorin/isoimperatorin could evidently increase the solubility of imperatorin and isoimperatorin, the enhancing effect of isoimperatorin solubility is better than that of imperatorin.

This paper described the preparation and liver targeting traits of new solid lipid nanoparticles (SLN) containing floxuridinyl dibutyrate (FUDRB) modified with beta-D-galactosides (G2). FUDRB-SLN and FUDRB-G2SLN were prepared by thin layer ultrasonic technique. Transmission electron microscopy micrograph analysis demonstrated that the particle sizes of FUDRB-SLN and FUDRB-G2SLN were (137.5 +/- 11.1) nm and (95.0 +/- 10.7) nm. Drug loading were 9.64% and 8.56%, and entrapment efficiency were 99.81% and 96.23%, respectively. The concentrations of floxuridine (FUDR) in serum and some organs (liver, kidney and lung) were determined by RP-HPLC after iv administration of SLN. FUDR release was confirmed, and a significant enrichment of SLN modified with G2 was observed in liver with G2 complex (targeting rates of SLN-G2 was 8.28 for liver) in comparison with FUDR-sol (targeting rate was 2.56). FUDR could be detected in liver in mice at 480 min after iv administration of FUDRB-G2SLN. These results suggested that incorporation of G2 (4%-5%, g/g) into SLN enhanced the liver targeting-ability of FUDRB. SLN containing G2 could be a useful drug carrier system for liver targeting.

Fourier transform infrared spectroscopy (FTIR) was applied to study the decomposition process postmortem in rat lung tissue and provided a new method for the estimation of postmortem interval (PMI). The results demonstrated that, with the PMI increasing, the peak position of main absorbance bands showed no significant difference, but there was obvious variance of intensity: (1) The intensity of 1080 and 1241 cm(-1) related to nucleic acid tended to decrease. (2) The intensity ratio at Amide I (I1647) and II (I1541) decreased since death. The intensity of 1338 and 1313 cm(-1) increased lightly. (3) The intensity at 1460, 1400 and 1170 cm(-1) showed no significant difference. (4) A new band at 1120 cm(-1) appeared since 72 h after death and its intensity increased from 72 to 144 h postmortem. The authors' preliminary results suggest that it may be possible for FTIR to become an effective method to estimate the PMI in forensic practice.

Fourier transform infrared spectroscopy (FTIR) was applied to study the difference of vital reaction following skin injury close to death in mouse and provided the evidence for forensic practice. The results demonstrated that vital 5 min, postmortem and normal groups showed significant differences in the wave form and intensity: (1) The intensity at 3 007 and 1 745 cm(-1) related to lipid for the vital injury was higher than that for the postmortem; (2) The intensity at 1 160 cm(-1) related to carbohydrate for the vital injure increased more compared to the postmortem; (3) The intensity of the band at 1 640 cm(-1) related to amide I band for the injury groups was higher than the normal, but it was the lowest for the vital injury. These results show that it will be possible for FTIR to become an effective method to determine the vital reaction of injury close to death in forensic practice.

To study the technological parameters of the extraction process of the total alkaloids from Caulopyhllum robstum.Taspine, whiVh is main component of the total alkaloids from Caulopyhllum robustum, was selected as an evaluating marker and determined by HPLC. The orthogonal test was used to optimize extracting conditions in the process of acid water extraction. Then the optimized conditions for purification using cation exchange resin were investigated.The optimized conditions in the process of acid water extraction were 1% hydrochloric acid as much as seven times of the medicine amount for 24hs and three times. Then the extraction of acid water was purified with a column of macroporous cation exchange resin LSD001 at 2 ml/min of flow rate, then eluted with 10BV of 4% aqueous ammonia ethanol. The extraction ratio of the total alkaloids was 1. 35% and the content of taspine of the total alkaloids was 6. 80%.This technology is simply, cheap effective and feasible for manufacture in great scale.