Garcinia, a kind of dry resin secreted by Garcinia hanburyi Hook. F. G., is a traditional Chinese medicine with various biological functions such as detoxification, anti-inflammatory, and anthelmintic activities. Recent studies suggest that garcinia has potential anticancer activity. Increasing evidences indicate that the main active monomer gambogic acid isolated from garcinia can inhibit the growth of various cancer cells. Neogambogic acid is an isolated compound with a similar chemical structure as gambogic acid. Preliminary studies show that the neogambogic acid can selectively inhibit the growth of various cancer cells, and has a broader antitumor activity and lower toxicity than gambogic acid. In this review, we summarize the advances made in the investigation of the anti-tumor effect of neogambogic acid in recent years.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; chemistry ; Garcinia ; chemistry ; Humans ; Neoplasms ; drug therapy ; Plant Extracts ; administration & dosage ; chemistry ; Xanthenes ; administration & dosage ; chemistry

The aim of this paper was to observe the effect of gambogenic acid on angiogenesis of lung cancer and its preliminary mechanism. After culturing lung adenocarcinoma A549 cells, the conditioned medium was treated with gambogenic acid and then used to culture human umbilical vein endothelial cells (HUVECs) to establish the indirect contact cell co-culture system. A two-dimensional culture model of HUVEC was established with matrigel to observe the effect of gambogenic acid on angiogenesis. DAPI staining was used to observe the morphological changes in HUVEC cells after treatment with gambogenic acid under the fluorescence microscope. Annexin V-FITC/PI staining and flow cytometry analysis were used to determine gambogenic acid's effect on HUVEC cell apoptosis rate. The protein expressions of PI3K, p-PI3K, Akt, p-Akt were measured by Western blot. PTEN-siRNA was transfected into cells, and RT-PCR was used to detect the expression levels of PI3K and Akt genes. Gambogenic acid can significantly inhibit angiogenesis, and its inhibitory effect was dose-dependent. DAPI staining showed apoptotic morphological features of HUVEC cells under fluorescence microscope. Annexin V-FITC/PI staining showed that gambogenic acid induced apoptosis in HUVECs. The results of Western blot showed that the expressions of p-PI3K and p-Akt protein were down-regulated with gambogenic acid, while the expressions of PI3K and Akt protein was insignificant. The results of RT-PCR indicated that the expressions of PI3K and Akt protein were up-regulated by PTEN siRNA. Gambogenic acid can inhibit angiogenesis in lung cancer in vitro, and the mechanism of inhibiting angiogenesis may be related to the PI3K/Akt signaling pathway.
A549 Cells ; Apoptosis ; Coculture Techniques ; Human Umbilical Vein Endothelial Cells ; drug effects ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Neovascularization, Pathologic ; pathology ; PTEN Phosphohydrolase ; genetics ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Transfection ; Xanthenes ; pharmacology

BACKGROUND: Cellulite is a 'cottage cheese-like' cutaneous change caused by subcutaneous fat bulging into the dermis that usually leads to cosmetic problems. Slimming cream containing 3.5% water-soluble caffeine and xanthenes exhibits a lipolytic effect with penetration into the dermis. OBJECTIVE: To evaluate the efficacy and safety of slimming cream for the treatment of cellulite. METHODS: Fifteen subjects with cellulite applied slimming cream to the thighs and inner side of the upper arms twice daily for 6 weeks. Efficacy was assessed using a standard visual scale, changes in the circumferences of the thighs and upper arms, and patient satisfaction by a questionnaire at baseline, week 3, and week 6. Safety was assessed by inquiring about adverse events through questionnaires. RESULTS: The standard visual scale score improved significantly by 0.49 points (19.8%) at week 6. Thigh and upper-arm circumferences decreased by 0.7 cm (1.7%) and 0.8 cm (2.3%), respectively, at week 6. Slight itching and transient flushing were commonly reported, but no serious adverse event occurred. CONCLUSION: The slimming cream tested appears to be effective for the treatment of cellulitis without serious adverse effects. However, additional large clinical trials are required to confirm the efficacy and safety of slimming cream for the treatment of cellulitis.
Arm ; Caffeine* ; Cellulitis ; Dermis ; Flushing ; Patient Satisfaction ; Pruritus ; Subcutaneous Fat ; Thigh ; Xanthenes* ; Surveys and Questionnaires

To investigate the neuroprotective of ligustilide (LIG) against glutamate-induced apoptosis of PC12 cells, cell viability were examined by MTT assay. Flow cytometry was applied to assay cell apoptosis rate. Intracellular calcium concentration was measured by using fluorescent dye Fluo-3/AM. Cytochrome C (Cyt C), Caspase-3, Bax and Bcl-2 protein expression were assayed by western blot. The results showed that glutamate is cytotoxic with an inhibitory concentration 50 (ID50) of 15 mmol · L(-1). Pretreatment with LIG (1, 5, 15 μmol · L(-1)) significantly improved cell viability. The apoptosis rate in glutamate-induced PC12 cells was 13.39%, and decreased in the presence of LIG (1, 5, 15 μmol · L(-1)) by 9.06%, 6.48%, 3.82%, separately. Extracellular accumulation of Ca2+ induced by glutamate were significantly reduced by LIG. The results of western blot manifested that pretreatment LIG could decrease the release of Cyt C from mitochondria, down-regulate Caspase-3 protein expression and up-regulate Bcl-2/Bax ratio, thereby protects PC12 cells from apoptosis. In summary, LIG had protective effect on glutamate-induced apoptosis in PC12 cells through attenuating the increase in intracellular Ca2+ concentration, and inhibiting the release of Cyt C from mitochondria to cytoplasm.
4-Butyrolactone ; analogs & derivatives ; pharmacology ; Aniline Compounds ; Animals ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; Calcium ; metabolism ; Caspase 3 ; metabolism ; Cell Survival ; Cytochromes c ; metabolism ; Glutamic Acid ; adverse effects ; Mitochondria ; metabolism ; PC12 Cells ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Xanthenes ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo study whether the analgesis of oxymatrine (OMT) affects N-type voltage-gated calcium channels (VGCCs).

METHODSTotally 45 mice were randomly divided into the sham-operation group, the model group [established by partial sciatic nerve ligation (PSNL)] , and the OMT treatment group according to random digit table, 15 in each group. The dorsal root ganglions (DRG) were separated in PSNL pain model mice. Intracellular calcium concentration ([Ca2+]i) was determined with Fluo-3 AM immunofluorescent probe in cultured DRG neurons. Different protein expression levels of N-type (Cav2. 2) and L-type ( Cav1. 3) among VGCCs from brain and DRG tissues were detected with Western blot.

RESULTSCompared with the sham-operation group, [Ca2+]i, increased in cultured DRG neurons (P <0. 05) , protein expression levels of Cav2. 2 in the brain tissue increased (P <0. 05), protein expression levels of Cav2. 2 in DRG tissues decreased in the model group (P <0. 01). Compared with the model group, [Ca2+]i, decreased in cultured DRG neurons (P < 0. 05), protein expression levels of Cav2. 2 in the brain tissue decreased (P <0. 01), protein expression levels of Cav2. 2 in DRG tissues increased in the OMT treatment group (P <0. 01). There was no statistical difference in Cav1. 3 expressions in cultured DRG neurons and the brain (P >0. 05).

CONCLUSIONAnalgesic effect of OMT might be related to Cav2. 2 channel mediated calcium ion flux.

Alkaloids ; pharmacology ; Analgesia ; methods ; Analgesics ; pharmacology ; Aniline Compounds ; Animals ; Calcium ; Calcium Channels, N-Type ; physiology ; Ganglia, Spinal ; Mice ; Neurons ; Pain ; Quinolizines ; pharmacology ; Xanthenes

We prepared protoplasts from Salvia miltiorrhiza Bunge suspension culture cells. Then, the protoplasts' vitality and functions were tested by fluorescein diacetate staining method and Fluo-3/AM flourescent probe. The optimal condition of protoplast isolation was Cellulase R-10 1.5%, Pectinase Y-23 0.3%, Macerozyme R-10 0.5%, 40 r/min 12 h, 600 r/min 5 min, and the protoplasts yield was 1.1x10(6) cells/g FW, the vitality was more than 95% by using fluorescein diacetate staining method. It has been confirmed that calcium fluorescent probe Fluo-3/AM can be successfully loaded into protoplasts.
Aniline Compounds ; chemistry ; Cell Culture Techniques ; Cellulase ; chemistry ; Fluorescent Dyes ; chemistry ; Protoplasts ; chemistry ; Salvia miltiorrhiza ; growth & development ; Xanthenes ; chemistry

Study on the effects of Astragali Radix main active flavone calycosin-7-O-β-D-glucoside on Saposhnikoviae Radix main active ingredients prim-O-glucosylcimifugin and cimifugin, a UPLC-MS/MS method for simultaneous determination of prim-O-glucosylcimifugin and cimifugin in rat plasma was established, and the comparative pharmacokinetics of prim-O-glucosylcimifugin and cimifugin after oral administration of prim-O-glucosylcimifugin and calycosin-7-O-β-D-glucoside-prim-O-glucosylcimifugin to rats were carried out, which might be conductive in exploring the rationality of Astragali Radix - Saposhnikoviae Radix herb couple. Twelve male SD rats were divided into two groups. Prim-O-glucosylcimifugin and cimifugin in rat plasma of different time points after oral administration of prim-O-glucosylcimifugin and calycosin-7-O-β-D-glucoside - prim-O-glucosylcimifugin to rats were determinated. And the main pharmacokinetic parameters were investigated using DAS 3. 2. 4. The established method was rapid, accurate and sensitive for simultaneous determination of prim-O-glucosylcimifugin and cimifugin in rat plasma. The analysis was performed on a Waters Acquity BEH C18 column (2.1 mm x 100 mm, 1.7 μm) with the mixture of acetonitrile and 0.1% formic acid/water as mobile phase, and the gradient elution at a flow rate of 0.3 mL x min(-1). The analytes were detected by tandem mass spectrometry with the electrospray ionization (ESI) source and in the multiple reaction monitoring (MRM) mode. Compared with prim-O-glucosylcimifugin group, the AUC(0-t)., and AUC(0-∞) of p-O-glucosylcimifugin as well as the C(max) of cimifugin significantly increased (P < 0.05) in calycosin-7-O-β-D-glucoside-prim-O-glucosylcimifugin group. Calycosin-7-O-β-D-glucoside could enhance the absorption of prim-O-glucosylcimifugin and cimifugin and improve the bioavailability, explaining preliminarily the rationality of Astragali Radix-Saposhnikoviae Radix herb couple.
Animals ; Chromatography, High Pressure Liquid ; Chromones ; blood ; pharmacokinetics ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacokinetics ; Glucosides ; blood ; pharmacology ; Isoflavones ; blood ; pharmacology ; Male ; Monosaccharides ; blood ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Xanthenes ; blood ; pharmacokinetics

OBJECTIVETo discuss the mechanism of gambogenic acid (GNA) in inducing the apoptosis of melanoma B16 cells.

METHODThe inhibitory effect of GNA on the proliferation of B16 cells was measured by the methyl thiazolyl tetrazolium (MTT) assay. The effect of GNA on B16 cells was detected by the Hoechst 33258 staining. The transmission electron microscopy was used to observe the ultra-structure changes of B16 cells. The changes in PI3K, p-PI3K, Akt, p-Akt, p-mTOR, PTEN proteins were detected by the Western blotting to discuss the molecular mechanism of GNA in inducing the apoptosis of B16 cells.

RESULTGNA showed a significant inhibitory effect in the growth and proliferation of melanoma B16 cells. The cell viability remarkably decreased with the increase of GNA concentration and the extension of the action time. The results of the Hoechst 33258 staining showed that cells processed with GNA demonstrated apparent apoptotic characteristics. Under the transmission electron microscope, B16 cells, after being treated with GNA, showed obvious morphological changes of apoptosis. The Western blot showed a time-dependent reduction in the p-PI3K and p-Akt protein expressions, with no change in p-PI3K and p-Akt protein expression quantities. The p-mTOR protein expression decreased with the extension of time, where as the PTEN protein expression showed a time-dependent increase.

CONCLUSIONGNA could inhibit the proliferation of melanoma B16 cells and induce their apoptosis within certain time and concentration ranges. Its mechanism in inducing the cell apoptosis may be related to PI3K/Akt/mTOR signaling pathways.

Animals ; Apoptosis ; drug effects ; Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Melanoma ; metabolism ; pathology ; ultrastructure ; Mice ; Microscopy, Electron, Transmission ; Microscopy, Fluorescence ; PTEN Phosphohydrolase ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; metabolism ; Terpenes ; pharmacology ; Xanthenes ; Xanthones ; pharmacology

Objective: To evaluate and compare the effects of bevacizumab, mitoinycin-C (MMC), 5-fluorouracil (5-FU), and triamcinolone acetonide (TA) on the viability of cultured human Tenon's capsule fibroblasts (cHTF) in vitro.

Methods: Human Tenon's fibroblasts (HTF) were harvested and cultured in a Roswell-Park-Memorial 1-Institute (RPMI) media. MMC, 5-FU, bevaciz. umab, and TA were administered to the cHTF at 3-fold decreasing concentrations starting from 20 ug, 5 mg, 25 mg, and 4 mg respectively. A negative control/untreated group containing RPMI media only was included in the study. Fibroblast cell viability was assessed using resazurin fluorim etric assay. Half¬maximal inhibitory concentration (IC50) was computed for agents which showed significant decrease in cHTF viability compared to the untreated group.

Results: There was no significant difference in cH IF viability between the untreated control group compared to 5-FU (p=0.97), bevacizumab (p=0.10), and TA (p=0.06) groups. Mitomycin-C showed a significant decrease in cHTF viability (p<0.001) which was dose dependent. The IC50 of MMC was computed at 12.16 ug using the prism software.

Conclusion: Mitomycin-C demonstrated dose-dependent decrease in viability of cultured human Tenon's fibroblasts. 5-FU, bevacizumab, and triamcinolone did not show this effect.

Key Words: Mitomycin-C, 5-fluorouracil, Bevaciz. umab, Tria. mcinolone acetonide, Fibroblast, Trabeculectomy

Human ; Male ; Female ; .humans ; Mitomycin ; Triamcinolone Acetonide ; Trabeculectomy ; Resazurin ; Bevacizumab ; Fluorouracil ; Cell Survival ; Control Groups ; Inhibitory Concentration 50 ; Tenon Capsule ; Xanthenes ; Oxazines ; Antibodies, Monoclonal, Humanized ; Fibroblasts ; Software

To simultaneously determine paeoniflorin, ferulic acid, prim-O-glucosylcimifugin and 4'-O-beta-glucopyranosyl-5-O-methylvisamminol in Zhengtian pills. In the test, Insertil ODS-C18 column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.05% phosphoric acid solution as the mobile phase for gradient elution. The flow rate was 1.0 mL x min(-1), the column temperature was 30 degrees C and the detection wavelength was 230 nm. According to the results of the test, paeoniflorin, ferulic acid, prim-O-glucosylcimifugin and 4'-O-beta-glucopyranosyl-5-O-methylvisamminol showed good linear relations between peak areas and sample sizes in 11.37-170.5, 2.188-32.82, 2.896-43.44, and 3.000-45.00 mg x L(-1) (r = 0.999 9, 0.999 9, 1.000 0, 1.000 0), respectively. The average recoveries (n = 6) were 102.3% (RSD 1.2%), 99.71% (RSD 1.9%), 101.2% (RSD 1.2%), and 99.40% (RSD 2.4%), respectively. The above four components were determined in five batches of samples by using the established method, with satisfactory results. The method was so simple, accurate and highly reproducible that it could be used for quality control of the four components in Zhengtian pills.
Benzoates ; analysis ; Bridged-Ring Compounds ; analysis ; Chromatography, High Pressure Liquid ; methods ; Coumaric Acids ; analysis ; Drugs, Chinese Herbal ; analysis ; standards ; Glucosides ; analysis ; Monosaccharides ; analysis ; Monoterpenes ; Quality Control ; Xanthenes ; analysis