Une new flavonoids named as notabilisin K (1), together with four known compounds, morusin (2), mulberrofuran A (3), neocyclomorusin (4) and mornigrol F (5) are separated from 95% ethanol extracts of the twigs of Morus notabilis. Compounds 2-5 are separated from this plant for the first time. Notabilisin I, notabilisin J exhibits certain effect against cells of HCT-116, HepG2 and A2780 with IC50 values ranging from 1.47 μmol x L(-1) to 5.46 μmol x L(-1). Morusin exhibits strong effect against five kinds of human cancer cells (BGC823, A2780, HCT-116, HepG2 and NCI-H1650) with IC50 values ranging from 0.74 μmol x L(-1) to 1.58 μmol x L(-1).
Antineoplastic Agents, Phytogenic ; chemistry ; Benzofurans ; chemistry ; Flavonoids ; chemistry ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Morus ; chemistry ; Plant Extracts ; chemistry ; Terpenes ; chemistry

Ten flavonoids were isolated from the 95% ethanol extract of the seeds of Alpinia galanga Willd. with a combination of various chromatographic techniques, including silica gel, Sephadex LH-20 and preparative HPLC. On the basis of spectroscopic data analysis, they were elucidated as (2R, 3S)-pinobaksin-3-cinnamate (1), (2R, 3R)-pinobaksin-3-cinnamate (2), pinocembrin (3), pinobaksin (4), 3-O-acetylpinobaksin (5), galangin (6), galangin-3-methylether (7), kumatakenin (8), 3-methylkaempferol (9) and (2R, 3R)-3, 5-dihydroxy-7-methoxyflavanone (10). Among them, compound 1 is a new compound, compounds 2, 5 and 10 were isolated from the genus Alpinia for the first time, and others were isolated from this plant for the first time.
Alpinia ; chemistry ; Benzopyrans ; chemistry ; isolation & purification ; Cinnamates ; chemistry ; isolation & purification ; Flavanones ; chemistry ; isolation & purification ; Flavonoids ; chemistry ; isolation & purification ; Kaempferols ; chemistry ; isolation & purification ; Molecular Structure ; Plants, Medicinal ; chemistry ; Seeds ; chemistry

The chemical constituents of Poria cocos were studied by means of silica gel, ODS column chromatography, Sephadex LH-20 and preparative HPLC. Thirteen compounds were isolated from this plant. By analysis of the ESI-MS and NMR data, the structures of these compounds were determined as tumulosic acid (1), dehydrotumulosic acid (2), 3beta, 5alpha-dihydroxy-ergosta-7, 22-dien-6-one (3), 3beta, 5alpha, 9alpha-trihydroxy-ergosta-7, 22-diene -6-one (4), ergosta-7, 22-diene-3-one (5), 6, 9-epoxy-ergosta-7,22-diene-3-ol (6), ergosta-4,22-diene-3-one (7), 3beta, 5alpha, 6beta-trihydroxyl-ergosta-7,22-diene (8), ergosta-5, 6-epoxy-7,22-dien-3-ol (9), beta-sitosterol (10), ribitol (11), mannitol (12), and oleanic acid 3-O-acetate (13), respectively. Compounds 3-13 were isolated from the P. cocos for the first time.
Drugs, Chinese Herbal ; chemistry ; Organic Chemicals ; analysis ; Poria ; chemistry

OBJECTIVE Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease with a high morbidity around 1/1000-1/400, characterized by progressive enlargement of fluid-filled cysts derived from renal tubular epithelial cells. Massive cysts gradually compress renal parenchyma destroying normal renal structures and compromising renal functions. Unfortunately, it will cause end-stage renal disease in most of the patients but without effective therapy now, who have to live on hemodialysis or kidney transplantation. Based on this present situation, it is of great significance to find early intervention to inhibit renal cyst development. The projective of this study was to investigate whether Ganoderma triterpenes (GT) can inhibit renal cyst development and study the related mechanism. METHODS and RESULTS First, we used MDCK cyst model, cultivated MDCK cells in vitro to form fluid-filled cysts surrounded by monolayer cells. GT inhibited MDCK cyst formation significantly, and inhibited cyst enlargement dose-dependently proving GT cyst inhibition in vitro. Then we used an embryonic kidney cyst model, wile-type mice kidneys were taken out on embryonic day 13.5 to form renal cysts stimulated with 8-Br-cAMP. GT inhibited embryonic kidney cyst development significantly in a dose-dependent and reversible manner proving GT cyst inhibition at organ level. Furthermore, we used two ADPKD mouse models with severe cystic kidney disease phenotypes. GT dramatically inhibited renal cyst development, decreased ADPKD mouse kidney volume and the cyst index inside proving GT cyst inhibition in vivo. By Western blot, we proved GT down-regulated Ras/MAPK signal pathway without detectable effect on mTOR signal pathway both in MDCK cells and two ADPKD mouse kidneys. CONCLUSION GT retard renal cyst development both in vitro and in vivo significantly. The related mechanisms were involved in GT promoting renal tubular epithelial cell differentiation, down-regulating intracellular cAMP level and Ras/MAPK signal pathway.

AIM:To investigate the influence of signal transducer and activator of transcription 3(STAT3)on Warburg effect in the malignant transformation of WB-F344 rat hepatic oval cells.METHODS:The WB-F344 cells were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)and hydrogen peroxide(H2O2)to induce the malignant trans-formation.Evaluation of the transformed cells were measured by the soft agar colony formation assay and DNA aneuploidy with flow cytometry.The levels of glucose and lactate in the culture medium of the cells were detected by chromatography. The protein levels of alpha-fetoprotein(AFP),STAT3,p-STAT3 and glucose transporter 2(GLUT2)in the cells were ex-amined by Western blot analysis.The cell proliferation were evaluated by WST-1 assay,viable cell counting,measuring the S-phase fraction(SPF)and proliferation index(PI)using the data from flow cytometry analysis,and detecting proliferating cell nuclear antigen(PCNA)protein expression by Western blot.RESULTS:Compared with the control cells,the forma-tion of colonies in soft agar(P<0.05)and DNA aneuploidy(P<0.01)were elevated in transformed cells,and the ex-pression level of AFP was also augmented(P<0.05).The increases in the level of both glucose consumption(P<0.05) and lactate production(P<0.01)show that Warburg effect was enhanced in transformed cells.Meanwhile, the protein levels of GLUT2(P<0.01)and p-STAT3(P<0.01)in transformed cells were higher than those in the control cells.The cell proliferation parameters including SPF(P<0.01),PI(P<0.01), viable cell number and PCNA expression(P<0.01)in transformed cells were also elevated as compared with the control cells.Interestingly, stattic, an inhibitor of STAT3 activation,resulted in declines in glucose consumption(P<0.05)and lactate production(P<0.01)in the trans-formed cells.In addition,compared with transformed cells,formation of colonies in soft agar(P<0.01),DNA aneuploidy (P<0.01),AFP(P<0.05), GLUT2(P<0.05), and cell proliferation parameters including SPF(P<0.01), PI (P<0.01),viable cell number(P<0.05)and PCNA expression(P<0.05)were also decreased following stattic treat-ment in transformed cells.CONCLUSION:STAT3 promotes Warburg effect and cell proliferation probably by upregula-ting GLUT2 expression in the malignant transformation of hepatic oval cells.

Objective To compare the effects of moxibustion at different temperatures on blood lipid and TRPV1 in dorsal root ganglion with hyperlipidemia rats; To verify the correlation between efficacy of adjusting fat of moxibustion with activating of TRPV1. Methods The rat model of hyperlipidemia was made by high fat diet. 60 SD mice were randomly divided into four groups: control group, model control group, the 38 ℃ moxibustion group and the 45 ℃ moxibustion group, with 15 mice in each group. Acupoints Shenque and Zusanli were chosen under moxibustion for 10 minutes each time, once another day, for 4 weeks, in the 38 ℃ moxibustion group and the 45 ℃moxibustion group. Blood was taken after intervention, and blood TC, TG, LDL-C and HDL-C of the mice were detected by oxidase method; the dorsal root ganglion was taken to detect the expression of TRPV1 mRNA by real-time fluorescence quantitative PCR. Results Compared with model group, blood lipid indexes in moxibustion groups had different changes, with statistical significance compared with 45 ℃ moxibustion group (P<0.05, P<0.01), and there was statistical significance between 38 ℃ moxibustion group and 45 ℃ moxibustion group (P<0.01); there was statistical significance in TRPV1 mRNA of dorsal root ganglion among 45 ℃ moxibustion group and other three groups (P<0.01). Conclusion The correlation between efficacy of adjusting fat of moxibustion with activating of TRPV1 has been confirmed.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the simultaneous determination of yogliptin and its metabolite in Wistar rat plasma. Linagliptin and dexamethasone were chosen as the internal standards of yogliptin and its metabolite, (R)-8-(3-hydroxypiperidine- -yl)-7-(but-2-yn-1-yl)-1-((5-fluorobenzo[d]thiazol-2-yl)methyl)-3-methyl- H-purine-2, 6 (3H, 7H)-dione, respectively. After a simple protein precipitation using acetonitrile as the precipitating solvent, both analytes and ISs were separated on a Grace Altima HP C18 column (2.1 mm x 50 mm, 5 microm) with gradient elution using methanol (containing 0.1% formic acid, 4 mmol x L(-1) ammonium acetate)-0.1% formic acid (containing 4 mmol x L(-1) ammonium acetate) as the mobile phase. A chromatographic total run time of 4.4 min was achieved. Mass spectrometric detection was conducted with electrospray ionization under positive-ion and multiple-reaction monitoring modes. Linear calibration curves for yogliptin and its metabolite were over the concentration range of 0.5 to 500 ng x mL(-1) with a lower limit of quantification of 0.5 ng x mL(-1). The intra- and inter- assay precisions were all below 14%, the accuracies were all in standard ranges. The method was used to determine the concentration of yogliptin and M1 in Wistar rat plasma after a single oral administration of yogliptin (27 mg x kg(-1)). The method was proved to be selective, sensitive and suitable for pharmacokinetic study of yogliptin and M1 in Wistar rat plasma.
Animals ; Chromatography, Liquid ; Dexamethasone ; blood ; Dipeptidyl-Peptidase IV Inhibitors ; blood ; pharmacokinetics ; Linagliptin ; blood ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry

OBJECTIVETo study the severity of periodontitis and risk factors in Chengdu.

METHODS202 periodontitis patients (65 male, 137 female), aged from 25 to 60, were requested to fill a questionnaire. Probing depth (PD), clinical attachment level (CAL), gingival recession and bleeding on probing (BOP) on 6 sites of each tooth were measured and recorded.

RESULTSThe mean PD, AL, gingival recession and BOP% of 202 subjects was (3.2 +/- 0.31) mm, (3.5 +/- 0.37) mm, (0.3 +/- 0.02) mm and 21.16%. 59% of subjects missed at least one tooth. 129 subjects suffered with initial to moderate periodontitis. 73 subject suffered with advanced periodontitis. 40, 86, 55 and 21 subjects had received college education, high school education, middle school education and primary school education. 18% of subjects had smoking history, 67% subjects had tea/coffee history, 66% of subjects had psychosocial problem, and only 8% of subjects had received regular periodontal treatment. There is no relationship between the severity of periodontitis and education.

CONCLUSIONIt is very important to develop an education program on oral healthy for people in Chengdu.

Adult ; Female ; Gingival Recession ; Humans ; Male ; Middle Aged ; Periodontal Attachment Loss ; Periodontal Index ; Periodontitis ; Risk Factors

BACKGROUNDInvasive pulmonary aspergillosis (IPA) is a severe and frequently fatal disease in patients receiving treatment with immunosuppressive agents such as cyclophosphamide. Aspergillus fumigatus (A. fumigatus) now is a leading cause of IPA. Dectin-1 and Toll-like receptor 2 (TLR2) are important pattern recognition receptors involved in immune responses to A. fumigatus in vitro. However, the expression of the two receptors during the infection of A. fumigatus in vivo is not completely understood. The effects of cyclophosphamide treatment on the expression of the receptors need to be further studied.

METHODSWe established different immune status in mice models with or without A. fumigatus infection. On days 1, 3 and 5 post inoculation, pulmonary tissues from mice of the different groups were harvested. Dectin-1 and TLR2 mRNA expression in the lungs of the mice were investigated by real-time PCR. The pulmonary fungal burden in the mice with A. fumigatus infection was also evaluated.

RESULTSIn the immunocompetent mice, three days after A. fumigatus inoculation, dectin-1 and TLR2 expression increased markedly compared with the normal control group. Cyclophosphamide inhibited the clearance of pathogens and the expression of dectin-1 with or without A. fumigatus infection in the lungs as well. There was no statistical difference in TLR2 expression between the different immune status groups.

CONCLUSIONSOur results suggest that in vivo, dectin-1 and TLR2 are activated during the experimental period which would provide a broad range of possibilities for a specific and effective inflammatory response to kill A. fumigatus. Inhibition of dectin-1 expression may be one of the mechanisms of cyclophosphamide in the development of IPA.

Animals ; Aspergillosis ; immunology ; microbiology ; Aspergillus fumigatus ; immunology ; physiology ; Cyclophosphamide ; pharmacology ; Immunosuppressive Agents ; pharmacology ; Lectins, C-Type ; Lung ; drug effects ; metabolism ; microbiology ; Male ; Membrane Proteins ; genetics ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins ; genetics ; Polymerase Chain Reaction ; Toll-Like Receptor 2 ; genetics

OBJECTIVETo study the chemical constituents from leaves of Sapium sebiferum.

METHODThe compounds were isolated and purified by silic gel column chromatography and preparative HPLC. The structures were identified by various spectral evidence.

RESULTNine compounds were obtained and they were shikimic acid (1), kaempferol (2), quercetin (3), isoquercein (4), hyperin (5), kaempferol-3-O-beta-D-glucopyranoside (6), kaempferol-3-O-beta-D-glueopyranoside (7), gallic acid (8), rutin (9).

CONCLUSIONCompounds 1, 5, 6 and 7 are isolated from this genus for the first time and compound 9 is isolated from this plant for the first time.

Chromatography, Gel ; Chromatography, High Pressure Liquid ; methods ; Kaempferols ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Quercetin ; analogs & derivatives ; chemistry ; isolation & purification ; Rutin ; chemistry ; isolation & purification ; Sapium ; chemistry ; Shikimic Acid ; chemistry ; isolation & purification