Animals ; Anti-HIV Agents ; chemistry ; pharmacology ; Furans ; pharmacology ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; HIV-1 ; drug effects ; Humans ; Keto Acids ; chemistry ; pharmacology ; Molecular Structure ; Naphthyridines ; pharmacology ; Triazoles ; pharmacology

OBJECTIVETo observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism.

METHODSCultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining.

RESULTSMTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment.

CONCLUSIONRITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; Dacarbazine ; analogs & derivatives ; pharmacology ; Furans ; pharmacology ; Glioblastoma ; drug therapy ; Humans

We assessed the effects of furan and lycopene on the histopathological and biochemical changes on lungs, body and lung weights, and food consumption of rats. Furan and diabetes caused histopathological changes, increment in malondialdehyde levels, and decrease in antioxidant enzyme activities. Lycopene showed a protective effect against these damages, except for glutathione-S-transferase and glutathione peroxidase activities. Consequently, furan and diabetes resulted in lung toxicity. Our findings demonstrate that furan treatment resulted in more alterations in histology and biochemical parameters in diabetic rats and lycopene showed protective effects against these alterations.
Animals ; Antioxidants ; pharmacology ; Carotenoids ; pharmacology ; Diabetes Mellitus, Experimental ; enzymology ; pathology ; Furans ; toxicity ; Lung ; drug effects ; enzymology ; pathology ; Male ; Rats, Wistar

AIMTo investigate anti-hypoxia protective roles of the effective component extracted from angelia injection using hypoxia injury model in mice and ECV304 cells separately.

METHODSThe survival time of mice was observed separately under normobaric and hypobaric hypoxia. The activity of ECV304 cells was tested by MTT assay, and the mortality rate was examined by Trypan blue exclusion assay to evaluate the pharmacodynamic effects.

RESULTSAfter exposed to hypoxia the survival time of mice was increased in medicine groups,compared with the control groups (P < 0.05). The cell survival rate was decreased and the cell mortality rate was increased after cells were exposed to hypoxia,while the cell survival rate was significantly increased (P < 0.01), and the cell mortality rate was significantly decreased (P < 0.1) in the medicine groups compared with the control groups.

CONCLUSIONThe effective component extracted from angelia injection can protect against the injury induced by hypoxia.

Animals ; Cell Hypoxia ; Cell Line ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Furans ; pharmacology ; Glycosides ; pharmacology ; Hypoxia ; drug therapy ; Male ; Mice

The paper aims to study the pharmacokinetic parameters of gastrodin in rats effected by compound compatibilitiy and different doses of Tiangou Jiangya capsule. The extracts from Gastrodiae Rhizoma( equivalent to gastrodin 16.82 mg x kg(-1) and Tiangou jiangya capsule (equivalent to gastrodin 8.410, 16.82, 33.64 mg x kg(-1)) were oral administrated to rats respectively. The plasma were taken at various time points and treated with acetonitrile to measure the contents of gastrodin by HPLC method. The mean plasma concentration-time data were analyzed by 3P97 pharmacokinetic software and the pharmacokinetic parameters between groups were treated by SPSS 16.0. The results showed that gastrodin in rat was fitted to one-compartment model, Cmax and AUC of Tiangou Jiangya capsule were in direct proportion to oral administration, and t1/2Ka had nothing to do with doses, which indicated that gastrodin was fitted first-order rate transfter process in vivo. Morever, comparison with the Gastrodiae Rhizoma extract, isodose gastrodin in Tiangou Jiangya capsule showed a significant decrease for Cmax, Ke and increase for t1/2Ke, V/Fc, this indicated that compound compatibility can delay the absorbtion of gastrodin, prolong the resident time and promote the distribution in vivo, but its bioavailability is not significantly effected.
Administration, Oral ; Animals ; Benzyl Alcohols ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Blood Pressure ; drug effects ; Female ; Flavonoids ; chemistry ; pharmacology ; Furans ; chemistry ; pharmacology ; Gastrodia ; chemistry ; Glucosides ; administration & dosage ; chemistry ; pharmacokinetics ; pharmacology ; Lignans ; chemistry ; pharmacology ; Male ; Rats ; Rats, Sprague-Dawley ; Software

OBJECTIVETo observe the protective effect of the Weinaokang (WNK) and its active compound bilobalide on focal cerebral ischemia reperfusion, and their mechanisms.

METHODThe 60-minute middle cerebral artery occlusion (MCAO) was adopted to establish the 24 h-14 d reperfusion model. The expression of Beclin-1 was detected by the Western blotting technique. The transmission electron microscopy was used to observe ultrastructural changes. Neurogenesis was detected by the immunofluorescence staining.

RESULTWNK (20, 10 mg x kg(-1), ig) or its active compound bilobalide (10, 5 mg x kg(-1), ig) could promote the generation of mature neurons (BrdU(+) -MAP-2+) at the ischemic side, and inhibit expression of autophagy-related gene Beclin-1, so as to reduce the neuron injury induced by focal cerebral ischemia reperfusion.

CONCLUSIONWNK and its active compound bilobalide can inhibit neuron autophagy and improve neurogenesis in ischemic peripheral area, suggesting that neurogenesis may be the intervention target for WNK to promote self-repairing of ischemic area.

Animals ; Autophagy ; drug effects ; Brain Ischemia ; drug therapy ; pathology ; physiopathology ; Cyclopentanes ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Furans ; pharmacology ; Ginkgolides ; pharmacology ; Male ; Neurogenesis ; drug effects ; Neurons ; ultrastructure ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control

The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase, acts as a "master switch" for cellular anabolic and catabolic processes, regulating the rate of cell growth and proliferation. Dysregulation of the mTOR signaling pathway occurs frequently in a variety of human tumors, and thus, mTOR has emerged as an important target for the design of anticancer agents. mTOR is found in two distinct multiprotein complexes within cells, mTORC1 and mTORC2. These two complexes consist of unique mTOR-interacting proteins and are regulated by different mechanisms. Enormous advances have been made in the development of drugs known as mTOR inhibitors. Rapamycin, the first defined inhibitor of mTOR, showed effectiveness as an anticancer agent in various preclinical models. Rapamycin analogues (rapalogs) with better pharmacologic properties have been developed. However, the clinical success of rapalogs has been limited to a few types of cancer. The discovery that mTORC2 directly phosphorylates Akt, an important survival kinase, adds new insight into the role of mTORC2 in cancer. This novel finding prompted efforts to develop the second generation of mTOR inhibitors that are able to target both mTORC1 and mTORC2. Here, we review the recent advances in the mTOR field and focus specifically on the current development of the second generation of mTOR inhibitors as anticancer agents.
Antineoplastic Agents ; pharmacology ; Cell Proliferation ; drug effects ; Furans ; pharmacology ; Humans ; Imidazoles ; pharmacology ; Indoles ; pharmacology ; Mechanistic Target of Rapamycin Complex 1 ; Mechanistic Target of Rapamycin Complex 2 ; Morpholines ; pharmacology ; Multiprotein Complexes ; antagonists & inhibitors ; Naphthyridines ; pharmacology ; Neoplasms ; pathology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; pharmacology ; Pyridines ; pharmacology ; Pyrimidines ; pharmacology ; Quinolines ; pharmacology ; Signal Transduction ; Sirolimus ; pharmacology ; TOR Serine-Threonine Kinases ; antagonists & inhibitors

AIMTo study the inhibition of oxygen consumption by annonaceous acetogenins (ACG) and their structure-activity relationship (SAR).

METHODSThe inhibition of oxygen consumption in chicken liver cell respiration by different structural ACG was studied by using oxygen electrode technique.

RESULTSSix ACG showed potent inhibitory effects like rotenone which was a classical inhibitor of mitochondrial complex I, and was more potent than complex IV inhibitor KCN. The IC50 values of six ACG for inhibiting oxygen consumption suggested that bistetrahydrofuran (THF) ACG was 7-11 times more active than non-THF ACG, and A1-type ACG was more potent than A2-type ACG.

CONCLUSIONThe terminal gamma-lactone was crucial for the inhibition of oxygen consumption. The distance between THF and gamma-lactone, the hydroxyl groups in the alkyl chain, were the important factors of SAR, but the 4-OH group possibly played some negative role in the exhibit of potent activity.

Acetogenins ; Animals ; Annona ; chemistry ; Cell Separation ; Chickens ; Fatty Alcohols ; chemistry ; pharmacology ; Furans ; chemistry ; isolation & purification ; pharmacology ; Lactones ; chemistry ; isolation & purification ; pharmacology ; Liver ; cytology ; Mitochondria, Liver ; drug effects ; metabolism ; Oxygen Consumption ; drug effects ; Plants, Medicinal ; chemistry ; Seeds ; chemistry ; Structure-Activity Relationship

OBJECTIVETo observe the effect of Tiangou Jiangya capsule on isolated rabbit aortic strips, and to discuss its antihypertensive mechanism.

METHODThe isolated rabbit aortic strips were placed in perfusion baths, and induced to contract by norepinephrine (NE), KCl and CaCl2 respectively, then Tiangou Jiangya capsule extraction was added to observe its effect on the contraction. The effect on intracellular Ca2+ dependent contraction and extracellular Ca2+ dependent contraction induced by NE were also studied.

RESULTThe Tiangou Jiangya capsule (1, 3, 5 g x L(-1)) can reduce the largest contract reaction of aortic strips induced by NE or CaCl2 (P < 0.01). It can reduce both intracellular Ca2+ dependent contraction and extracellular Ca2+ dependent contraction induced by NE (P < 0.01), and the effect on extracellular Ca2+ dependent contraction is more significant. But the Tiangou Jiangya capsule has no significant effect on KCl induced contraction.

CONCLUSIONTiangou Jiangya capsule can regulate intracellular Ca2+ concentration and help to relax the vascular smooth muscle. The mechanism could be regulating the receptor-operated Ca2+ channel. The effect on extracellular Ca2+ dependent contraction is more obvious than on intracellular Ca2+ dependent contraction induced by NE.

Animals ; Antihypertensive Agents ; pharmacology ; Aorta ; drug effects ; Benzyl Alcohols ; pharmacology ; Blood Pressure ; drug effects ; Calcium Chloride ; pharmacology ; Diuresis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Furans ; pharmacology ; Glucosides ; pharmacology ; In Vitro Techniques ; Lignans ; pharmacology ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; drug effects ; Norepinephrine ; pharmacology ; Potassium Chloride ; pharmacology ; Rabbits ; Renin-Angiotensin System ; drug effects ; Ventricular Function, Left ; drug effects

The late stages of the HIV-1 replication cycle are important to the overall replication cycle. During the late stages, HIV-1 replication undergoes the processes of assembly, release, and maturation, resulting in the production of a mature virus particle capable of infecting a new target cell. The structural protein Gag and its related gene (protein) play a central role in these pathways. The different regions of Gag worked in concert to drive production of a mature infectious particle through protein-protein, protein-RNA and protein-lipid interactions. The designed drug aimed directly at these stages can efficiently block the maturation and infectivity of HIV-1. In this article, the role of structural protein Gag and related gene (protein) in late stages of the HIV-1 replication cycle and related inhibitors is reviewed.
Amphotericin B ; analogs & derivatives ; chemistry ; pharmacology ; Anti-HIV Agents ; chemistry ; pharmacology ; Benzeneacetamides ; chemistry ; pharmacology ; Furans ; chemistry ; pharmacology ; Genes, gag ; HIV-1 ; drug effects ; physiology ; Humans ; Phenylurea Compounds ; chemistry ; pharmacology ; Piperidines ; chemistry ; pharmacology ; Succinates ; chemistry ; pharmacology ; Sulfur Compounds ; chemistry ; pharmacology ; Triterpenes ; chemistry ; pharmacology ; Virus Assembly ; drug effects ; Virus Release ; drug effects ; Virus Replication ; drug effects ; physiology ; gag Gene Products, Human Immunodeficiency Virus ; metabolism ; physiology