As exogenous ALA (5-aminolevulinic acid) esters can induce the production and accumulation of endogenous photosensitizer PpIX (protoporphyrin IX) in tumor tissues more effectively, they have been the most active photosensitizer prodrug in PDT(photodynamic therapy) field. In this article, along with the procedure of ALA esters based PDT, some primary mechanism and experimental results were considered, which include: first, cellular uptake of ALA esters and its conversion into ALA; second, the production and accumulation of endogenous photosensitizer PpIX induced by eNdogenous ALA esters; last, the photosensitization of PpIX.
Aminolevulinic Acid ; pharmacology ; Esters ; pharmacology ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; Prodrugs ; Protoporphyrins ; pharmacology

Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
Cytochrome P-450 Enzyme System ; metabolism ; Esters ; pharmacology ; Glycosides ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Oligosaccharides ; pharmacology ; Polygala ; chemistry ; Xanthones ; pharmacology

The aim of the present study was to investigate the influence of osmotic pressure on myocardial contractility and the possible mechanism. Electrical stimulation was used to excite papillary muscles of the left ventricle of Sprague-Dawley (SD) rats. The contractilities of myocardium in hyposmotic, isosmotic, and hyperosmotic perfusates were recorded. The influences of agonist and antagonist of the transient receptor potential vanilloid 4 (TRPV4) on the contractility of myocardium under hyposmotic, isosmotic and hyperosmotic conditions were observed. The results were as follows: (1) Compared with that under isosmotic condition (310 mOsm/L), the myocardial contractility was increased by 11.5%, 21.5% and 25.0% (P<0.05) under hyposmotic conditions when the osmotic pressure was at 290, 270 and 230 mOsm/L, respectively; and was decreased by 16.0%, 23.7% and 55.2% (P<0.05) under hyperosmotic conditions when the osmotic pressure was at 350, 370 and 390 mOsm/L, respectively. (2) When ruthenium red (RR), an antagonist of TRPV4, was added to the hyposmotic perfusate (270 mOsm/L), the positive inotropic effect of hyposmia was restrained by 36% (P<0.01); and when RR was added to the hyperosmotic perfusate (390 mOsm/L), the inhibitory effect of hyperosmia on myocardial contractility was increased by 56.1% (P<0.01). (3) When 4-α-phorbol-12,13-didecanoate (4α-PDD), an agonist of TRPV4, was added to the isosmotic perfusate (310 mOsm/L), the myocardial contractility did not change; and when 4α-PDD was added to the hyperosmotic perfusate (390 mOsm/L), the inhibition of myocardial contractility by hyperosmia was increased by 27.1% (P<0.01). These results obtained indicate that TRPV4 is possibly involved in the osmotic pressure-induced inotropic effect.
Animals ; Heart ; physiology ; Myocardial Contraction ; physiology ; Osmotic Pressure ; Phorbol Esters ; pharmacology ; Rats ; Rats, Sprague-Dawley ; TRPV Cation Channels ; physiology

OBJECTIVETo investigate the inhibitory effect of arsenic trioxide (As₂O₃) combined with tetradecanoylphorbol acetate (TPA) on the proliferation of Kasumi-1 cell line and its mechanism.

METHODSKasumi-1 cells were treated with 200 nmol/L TPA, different concentrations of As₂O₃ alone and combined with 200 nmol/L TPA. The proliferative inhibition rates were determined with CCK-8. Annexin V was adopted to detect apoptosis. Colony formation assay was used to determine the cloning efficiency. Flow cytometry was used to detect the cell differentiation and cell cycle changes. Western blot was employed to detect the expression of P38 and p-P38.

RESULTSThe proliferation inhibition rates of Kasumi-1 cells by TPA combined with different concentrations of As₂O₃ (0.2, 2.0 and 20.0 mmol/L)for 48 h were (25.56 ± 7.29)%, (60.63 ± 6.64)%, and (73.37 ± 2.15)%, the apoptosis rates were (61.65 ± 2.62)%, (75.39 ± 1.04)%, and (89.95 ± 1.46)%, and the colony formation rates were (76.17 ± 2.06)%, (38.50 ± 1.87)%, and (18.53 ± 2.20)%, respectively, compared with the different concentrations of As₂O₃ alone groups, the difference was statistically significant (P<0.05). Cells treated with both TPA and As₂O₃ expressed more CD11b antigens compared with the cells exposed to As₂O₃ alone. TPA treated Kasumi-1 cells were arrested at G1 phase compared with the control group, while As₂O₃ increased the percentage of Kasumi-1 cells in the G2 phase. Combination treatment increased the expression of p-P38 of Kasumi-1 cells compared with the cells exposed to As₂O₃ alone.

CONCLUSIONTPA can enhance the effect of As₂O₃ on inducing apoptosis and regulating cell cycle, thereby enhancing its anti-leukemia effect.

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Oxides ; pharmacology ; Phorbol Esters ; pharmacology

A novel reaction-enzymatic ammonolysis discovered in the mid of 1990s has been demonstrated to be a very promising alternative in the preparation of optically pure compounds. The effects of organic solvent, initial water activity, temperature and additives on lipase Novozym435-catalyzed enantioselective ammonolysis of racemic phenylglycine methyl ester were investigated systematically in this paper. Enzymatic reaction of ammonolysis showed higher activity and enantioselectivity than the corresponding reaction of hydrolysis and alcoholysis.
Alcohols ; Ammonia ; Catalysis ; Dimethylformamide ; pharmacology ; Esters ; Glycine ; analogs & derivatives ; metabolism ; Hexoses ; pharmacology ; Hydrolysis ; Lipase ; drug effects ; metabolism ; Organic Chemicals ; Solvents ; Surface-Active Agents ; pharmacology ; Temperature ; Water

The purpose of the present study was to investigate the effect of pravastatin on cholesteryl esters in foam cells of murine macrophages and the relation with caveolin-1. RAW 264.7 murine macrophages were coincubated with 80 mg/L oxidized low density lipoprotein (ox-LDL) and pravastatin (0~100 mumol/L) respectively for 24 h. When the best control concentration of pravastatin was confirmed, RAW 264.7 murine macrophages were coincubated with 80 mg/L ox-LDL and pravastatin of the best concentration respectively for 0, 6, 12, 24 h. Oil red O dyeing experiment was used to show the lipid droplets in foam cells. High performance liquid chromatography (HPLC) analysis was performed to determine the content of cellular cholesterol. The level of caveolin-1 was determined by Western blot analysis. The result showed that when macrophages were incubated with 80 mg/L ox-LDL, the ratio of cellular cholesteryl ester to total cholesterol (CE/TC) was beyond 50% through HPLC analysis, and a great deal of lipid droplets displayed in cells through Oil red O dyeing experiment, which manifested the formation of the foam cells. Pravastatin could decrease CE in foam cells in a concentration-dependent manner (1~100 mumol/L). At the concentration of 100 mumol/L, pravastatin decreased cellular CE more than 50%. The effects of pravastatin on the decrease of CE in murine macrophages also displayed a time-dependent manner (incubated with 100 mumol/L pravastatin from 6 to 24 h). Moreover, the expression of caveolin-1 was decreased when the macrophages were incubated with ox-LDL (80 mg/L), while treatment with pravastatin increased the level of caveolin-1 and displayed a concentration- and time-dependent manner. These results suggest that pravastatin could inhibit the development of foam cells through the decrease of cellular CE, which may be related to the upregulation of caveolin-1.
Animals ; Anticholesteremic Agents ; pharmacology ; Caveolin 1 ; metabolism ; Cell Line ; Cells, Cultured ; Cholesterol Esters ; metabolism ; Foam Cells ; metabolism ; Lipoproteins, LDL ; pharmacology ; Macrophages ; cytology ; Pravastatin ; pharmacology ; Rats

A new hexaketide acid esterified by the 17-hydroxyl group of 16,17-dihydroxycyclooctatin, namely 17-[16,17-dihydroxycyclooctatinyl]-hexaketide ester (1), a member of the group of rare bacterial diterpenes with a fused 5-8-5 ring system was isolated from strain Streptomyces sp. SR107. The structure was determined on the basis of its spectral data (H NMR, C NMR, H-H COSY, HSQC, HMBC, NOESY, IR and HR-ESI-MS). The antibacterial activity was also evaluated in this paper.
Anti-Bacterial Agents ; chemistry ; pharmacology ; Bacteria ; drug effects ; Diterpenes ; chemistry ; metabolism ; pharmacology ; Esters ; chemistry ; pharmacology ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Streptomyces ; chemistry

This study was designed to creat a new method for detecting the degree of cross-linked allogenic tissue based on fluorescent technique. The thoracic aorta of New Zealand rabbits were divided randomly into four groups according to the concentration of Glutaraldehyde (GA), which were group A (control group-with no GA), group B (cross-linked with GA of 0.625%), group C (1.25%), and group D (2.5%). Each group was cross-linked with GA and reacted with 5-FAMSE, and then the fluorescence intensity was observed via fluorescence microscopy (analyzed with Image-Pro Plus 6.0, a professional image analysis software). The differences between groups in order of fluorescence intensity were found to be: group A > roup B > group C > group D (P < 0.01). Meanwhile, the tissue proteins extracted from aorta in each group were submitted to conventional polyacrylamide gel electrophoresis (PGE) after being cross-linked with GA; the result from this method was compared with that from the method of 5-FAMSE. In group A, the tissue proteins extracted from the aorta cross-linked with GA were obviously less than those not cross-linked with GA. However, this phenomenom was not clearly seen among the B, C and D groups. Nevertheless, 5-FAMSE can detect the degree of cross-linkage more conveniently and directly.
Animals ; Aorta, Thoracic ; drug effects ; transplantation ; Bioprosthesis ; Blood Vessel Prosthesis ; Cross-Linking Reagents ; pharmacology ; Esters ; Female ; Fluoresceins ; Fluorescence ; Glutaral ; pharmacology ; Male ; Microscopy, Fluorescence ; Rabbits

OBJECTIVETo investigate the antidepressant components of Polygala tenuifolia.

METHODThe chromatographic method was used to isolate and purify the chemical constituents, their structures were identified by spectral analysis, MTT method was applied to investigate their cytotoxic activities.

RESULTNine compounds were isolated from the roots of P. tenuifolia. Their structures were identified as sibiricose A, (1), sibiricose A5 (2), tenuifoliside A (3) and 3', 6-disinapoyl sucrose (4), sibiricose A6 (5), 3, 4, 5-trimethoxycinnamate (6), polygalaxanthone III (7), tenuifolioses A (8), tenuifolioses H (9) and some compounds' activities to PC12 were observed.

CONCLUSIONCompound 1 was isolated from this plant for the first time. Compounds 2,3 could protect PC12 cells damage induced by P. tenuifolia.

Animals ; Antidepressive Agents ; chemistry ; isolation & purification ; pharmacology ; Esters ; chemistry ; isolation & purification ; pharmacology ; Mice ; PC12 Cells ; Plant Roots ; chemistry ; Polygala ; chemistry ; Rats ; Sucrose ; chemistry

AIMTo design and synthesize some cephalotaxine and drupacine derivatives with different substituentes on C3'-N of taxol side chain.

METHODSProtective side chain acid VI (4'S,5'R) was prepared from optically active (2'R,3'S) methyl beta-phenyl glycidate I in five steps. The desired acids were coupled with cephlotaxine and drupacine respectively in the presence of 2-DPC/DMAP, followed by acidic hydrolysis and acylating to give novel alkloid esters with different substitutes on C3'-N.

RESULTSThe seven new esters were studied for antitumor activity, the results showed that the antitumor activity was influenced by the substituentes on C3'-N.

CONCLUSIONIt might provide some rational basis for further structral modification.

Antineoplastic Agents, Phytogenic ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Colonic Neoplasms ; pathology ; Esters ; Harringtonines ; chemical synthesis ; chemistry ; pharmacology ; Humans ; KB Cells ; Liver Neoplasms ; pathology ; Molecular Structure