OBJECTIVETo observe the metabolism-based interaction of diphenytriazol and flavone compounds.

METHODSFlavone compounds kaempferol, isoharmnten and Elsholtzia blanda benth extract were chosen as the substrate of glucuronidation in the phase II metabolism. The metabolism was investigated in different rat liver microsome incubates pretreated with beta-naphthoflavone (BNF), diphenytriazol and tea oil (control). The concentrations of residual substrate were determined by HPLC. Quercetin and kaempferol were coincubated with diphenytriazol in control microsome to evaluate the inhibition for phase I metabolism. The concentration of diphenytriazol was determined by HPLC.

RESULTThe phase II metabolic activity of kaempferol, isoharmnten and Elsholtzia blanda benth extract in diphenytriazol-treated microsome was more potent than that in BNF-treated microsome (P<0.01). The phase I metabolism of diphenytriazol was markedly inhibited by quercetin and kaempferol, with the inhibition constants (Ki) (12.41 +/-0.26)microg . ml(-1) and (7.97 +/-0.08)microg . ml(-1), respectively.

CONCLUSIONDiphenytriazol demonstrates metabolism-based interaction with flavone compounds in vitro.

Abortifacient Agents ; metabolism ; pharmacology ; Animals ; Drug Interactions ; Female ; Flavones ; metabolism ; pharmacology ; Kaempferols ; metabolism ; pharmacology ; Plant Extracts ; pharmacology ; Quercetin ; metabolism ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Triazoles ; metabolism ; pharmacology

OBJECTIVETo study chemical constituents contained in Phymatopteris hastate and their antioxidant activity.

METHODChemical constituents were separated and purified from P. hastate by using such methods as silica gel, Toyopearl HW-40C and HPLC preparative chromatography. Their structures were identified by spectroscopic methods such as NMR. Furthermore, 1, 1-diphenyl-2-picryl-hydrazyl(DPPH) method was used to assess the antioxidant activity of each compound.

RESULTFourteen compounds were separated and identified as 4-O-beta-D-glucopyranosyl-ethyl-trans-caffeicate (1), kaempferlo-7-O-alpha-L-rhamnopyranside (2), kaempferol-3, 7-di-O-alpha-L-rhamnopyranoside (3), kaempferol-3-O-alpha-L-arabinofuranosyl-7-O-alpha-L-rhamnopyranoside (4), juglanin (5), naringin (6), naringenin-7-O-beta-D-glucopyranoside (7), trans-caffeic acid (8), trans-caffeic acid-3-O-beta-D-glucopyranoside (9), trans-cinnamic acid-4-O-beta-D- glucopyranoside (10), trans-melilotoside (11), cis-melilotoside (12), ethyl chlorogenate (13), protocatechuic acid (14). The antioxidation experiment showed an obvious antioxidant activity in compounds 1-9, 13-14.

CONCLUSIONAll of the compounds were separated from this genus for the first time. Among them, compound 1 was not seen in literature reports and assumed to be a new artifact derived from compound 9 and ethanol. Compounds 1-9, 13-14 showed a remarkable antioxidant activity.

Antioxidants ; pharmacology ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Flavanones ; analysis ; Kaempferols ; analysis ; Magnetic Resonance Spectroscopy

The purpose of this study was to explore the anti-leukemia effect of quercetin and kaempferol and its mechanism. The HL-60 cells were used as the leukemia models. The inhibitory effects of quercetin and kaempferol on growth of HL-60 cells was assessed by MTT assay. The effect of quercetin and kaempferol on cell cycle in HL-60 cells was detected by flow cytometry. The cytotoxic effect of these 2 drugs was analysed by single cell electrophoresis assay. Western blot analysis was used to study the apoptotic mechanism of HL-60 cells. The results showed that the quercetin and kaempferol had a significant anti-leukemia effect in vitro. The proliferation of HL-60 cells was significantly inhibited in dose-and time-dependent manners after treating with quercetin (r = 0.77) and kaempferol (r = 0.76) respectively, and the cytotoxicity of quercetin was superior to that of kaempferol. The quercetin and kaempferol induced G(2)/M arrest and apoptosis of HL-60 cells. The quercetin and kaempferol could down-regulate the survivin expression. It is concluded that the quercetin and kaempferol have significant anti-leukemia effect in vitro. Furthermore the apoptosis-inducing effect of quercetin is stronger than that of kaempferol, both of which induce apoptosis of HL-60 cells through depressing cell growth, arresting cell cycle and inhibiting expression of survivin.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Gene Expression Regulation, Leukemic ; HL-60 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Kaempferols ; pharmacology ; Quercetin ; pharmacology

OBJECTIVETo study, at the cytological level, the basic concept of Chinese medicine that "the Kidney (Shen) controls the bone".

METHODSKaempferol was isolated form Rhizoma Drynariae (Gu Sui Bu, GSB) and at several concentrations was incubated with opossum kidney (OK) cells, osteoblasts (MC3T3 E1) and human fibroblasts (HF) at cell concentrations of 2×10(4)/mL. Opossum kidney cell-conditioned culture media with kaempferol at 70 nmol/L (70kaeOKM) and without kaempferol (0OKM) were used to stimulate MC3T3 E1 and HF proliferation. The bone morphological protein receptors I and II (BMPR I and II) in OK cells were identified by immune-fluorescence staining and Western blot analysis.

RESULTSKaempferol was found to increase OK cell growth (P<0.05), but alone did not promote MC3T3 E1 or HF cell proliferation. However, although OKM by itself increased MC3T3 E1 growth by 198% (P<0.01), the 70kaeOKM further increased the growth of these cells by an additional 127% (P<0.01). It indicates that the kidney cell generates a previously unknown osteoblast growth factor (OGF) and kaempferol increases kidney cell secretion of OGF. Neither of these media had any significant effect on HF growth. Kaempferol also was found to increase the level of the BMPR II in OK cells.

CONCLUSIONSThis lends strong support to the original idea that the Kidney has a significant influence over bone-formation, as suggested by some long-standing Chinese medical beliefs, kaempferol may also serve to stimulate kidney repair and indirectly stimulate bone formation.

3T3 Cells ; Animals ; Cell Line ; Culture Media, Conditioned ; Intercellular Signaling Peptides and Proteins ; secretion ; Kaempferols ; pharmacology ; Kidney Tubules ; physiology ; secretion ; Medicine, Chinese Traditional ; Mice ; Opossums ; Osteoblasts ; chemistry

OBJECTIVETo investigate the effect of kaempferol on the pharmacokinetics of nifedipine (NFP) in rats.

METHODSTwenty male SD rats, weighing 220-260 g, were distributed randomly into 4 groups. The animals were fasted, but allowed free access to water for 12 h before the administration of drugs. NFP dissolved in corn oil was administered via gastric intubation to the rats in control group at a dose of 10 mg/kg. Kaempferol was administered orally to the other three groups with dose of 5, 10, 15 mg/kg, respectively, followed by oral administration of NFP 10 mg/kg. Blood samples were collected through tail vein in heparinized plastic microcentrifuge tubes before and after drug administration. The plasma concentration of NFP was monitored with reversed phase high-performance liquid chromatography (RP-HPLC). Nimodipine was used as the internal standard. Statistical data evaluation was performed with Student's t-test and one-way analysis of variances.

RESULTSThe maximal plasma concentration (C(max)) of the three treated groups were 0.51, 0.70 and 0.81 microg/ml, respectively. The area under the concentration-time curve (AUC(0-8)) were 1.81, 2.83 and 3.63 microg/(h.ml(-1)), respectively. The C(max), AUC(0-8) and the mean retention time (MRT(0-8)) of NFP were significantly increased by simultaneous oral treatment with kaempferol (P<0.01). On the other hand, there were no significant differences in the mean peak value time in plasma (T(max)) and the elimination half-life (t1/2(ke)) between the control and the treated groups.

CONCLUSIONThe concomitant oral use of kaempferol with NFP may influence the pharmacokinetic parameters of NFP in rats, which suggests that kaempferol might reduce the first-pass metabolism of NFP.

Animals ; Area Under Curve ; Calcium Channel Blockers ; pharmacokinetics ; Herb-Drug Interactions ; In Vitro Techniques ; Kaempferols ; pharmacology ; Male ; Nifedipine ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of kaempferol on proliferation of acute myeloid leukemia (AML) KG1a cells and its mechanism. METHODS: Human AML KG1a cells in logarithmic growth stage were taken and set at 25, 50, 75 and 100 μg/ml kaempferol group, another normal control group (complete medium without drug) and solvent control group (add dimethyl sulfoxide) were also set. After 24 and 48 hours of intervention, the cell proliferation rate was detected by CCK-8 assay. In addition, interleukin-6 (IL-6) combined with kaempferol group (Plus 20 μg/l IL-6 and 75 μg/ml kaempferol) was set up, 48 hours after culture, the cell cycle and apoptosis of KG1a cells were detected by flow cytometry, the mitochondrial membrane potential (MMP) of KG1a cells was detected by MMP detection kit (JC-1 method), and the expression of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway related proteins in KG1a cells were detected by Western blot. RESULTS: The cell proliferation rate of 25, 50, 75 and 100 μg/ml kaempferol group decreased significantly (P<0.05), and with the increase of kaempferol dose (r_{24 h}=-0.990, r_{48 h}= -0.999), the cell proliferation rate decreased gradually (P<0.05). The inhibitory effect of 75 μg/ml kaempferol on cell proliferation reached half of effective dose after 48 hours of intervention. Compared with normal control group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in 25, 50 and 75 μg/ml kaempferol group increased, while the S phase cell proportion, MMP, phosphorylated JAK2 (p-JAK2)/JAK2 and phosphorylated STAT3 (p-STAT3)/STAT3 protein expression decreased in a dose-dependent manner (r=0.998, 0.994, -0.996, -0.981, -0.997, -0.930). Compared with 75 μg/ml kaempferol group, the G₀/G₁ phase cell proportion and apoptosis rate of cells in IL-6 combined with kaempferol group decreased, while the S phase cell proportion, MMP, p-JAK2/JAK2 and p-STAT3/STAT3 protein expression increased significantly (P<0.05). CONCLUSION Kaempferol can inhibit KG1a cell proliferation and induce KG1a cell apoptosis, its mechanism may be related to the inhibition of JAK2/STAT3 signal pathway.
Humans ; STAT3 Transcription Factor/metabolism* ; Interleukin-6/metabolism* ; Kaempferols/pharmacology* ; Signal Transduction ; Apoptosis ; Janus Kinase 2 ; Cell Proliferation ; Leukemia, Myeloid, Acute

The growth environment of medicinal plants plays an important role in the formation of their medicinal quality. However, there is a lack of combined analysis studying the close relationship between the growth environment, chemical components, and related biological activities of medicinal plants. Therefore, this study investigated the effect of different soil moisture treatments on the efficacy to eliminate dampness and relieve jaundice and the flavonoid content of Sedum sarmentosum, and explored their correlation. The flavonoid content in the decoction of S. sarmentosum growing under field conditions with soil moisture levels of 35%-40%(T1), 55%-60%(T2), 75%-80%(T3), and 95%-100%(T4) was compared. The effects of these treatments on liver function parameters, liver inflammation, and oxidative damage in mice with dampness-heat jaundice were evaluated, and the correlation between pharmacological indicators and flavonoid content was analyzed. The results showed that the total flavonoid and total phenolic acid content in the decoction of S. sarmentosum were highest in the T1 treatment, followed by the T3 treatment. The content of quercetin, kaempferol, and isorhamnetin was highest in the T2, T1, and T3 treatments, respectively. Among the different moisture treatments, the T3 group of S. sarmentosum effectively reduced the levels of serum ALT, AKP, TBIL, DBIL, TBA, as well as hepatic TNF-α and IL-6 in mice with jaundice, followed by T2 treatment, especially in reducing AST level. The T4 treatment had the poorest effect. Correlation analysis showed a significant negative correlation between AST, ALT, AKP levels in mice and the total content of quercetin and the three flavonoids. MDA showed a significant negative correlation with the total flavonoid content and kaempferol. TNF-α exhibited a significant negative correlation with the content of isorhamnetin. In conclusion, S. sarmentosum growing under field conditions with a soil moisture level of 75%-80% exhibited the best efficacy to eliminate dampness and relieve jaundice. This study provides insights for optimizing the cultivation mode of medicinal plants guided by pharmacological experiments.
Mice ; Animals ; Flavonoids/chemistry* ; Plant Extracts/pharmacology* ; Quercetin ; Sedum/chemistry* ; Kaempferols ; Soil ; Tumor Necrosis Factor-alpha ; Plants, Medicinal/chemistry* ; Jaundice/drug therapy*

Six compounds have been isolated from the leaves of Pyrenacantha staudtii, two of which are new compounds. The new compounds have been characterized as kaempherol 3-O-beta-rhamnopyranosyl (1-->6)-beta-D-glucopyranoside (1) and 4-beta-glucopyranosyl-(2-furyl)-5-methy-1,2-glucopyranoside phenylmethanone (2). The known compounds are 3-pyridinecarboxylic acid (3), beta-sitosterol (4), sitosterol 3-O-beta-glucopyranoside (5) and taraxerol (6). Their structures were determined by spectroscopic and chemical evidences. The two new compounds together with 3-pyridinecarboxylic acid showed significant in vitro xanthine oxidase inhibitory activity. To the best of our knowledge, this is the first report of these compounds from this plant.
Enzyme Inhibitors ; chemistry ; isolation & purification ; pharmacology ; Glucosides ; chemistry ; isolation & purification ; pharmacology ; Kaempferols ; chemistry ; isolation & purification ; pharmacology ; Magnoliopsida ; chemistry ; Molecular Structure ; Niacin ; chemistry ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Xanthine Oxidase ; metabolism

OBJECTIVETo study the chemical constituents possessing cytotoxicity activity from Elaeagnus pungens.

METHODThe constituents were separated through repeated chromatographic methods and their structures were elucidated by spectral analysis.

RESULTFive compounds were isolated from the ethyl acetate ether extract of leaves of E. pungens. Their structures were elucidated as 4-hydroxybenzoic acid (1), 3, 3'-dimethoxyquercetin (2), caffeic acid methyl ester (3), methyl 3, 4-dihydroxybenzoate (4), spingic acid (5), 4-methoxylbenzoic acid (6), 3-methylkaempferol (7), kaempferol-3-O-beta-D-glucoside (8), dausosterol (9).

CONCLUSIONCompounds 1-8 were isolated from this plant for the first time.

Caffeic Acids ; chemistry ; isolation & purification ; pharmacology ; Cell Proliferation ; drug effects ; Elaeagnaceae ; chemistry ; HeLa Cells ; cytology ; Humans ; Kaempferols ; chemistry ; isolation & purification ; pharmacology ; Parabens ; chemistry ; isolation & purification ; pharmacology ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Quercetin ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology

OBJECTIVETo study the effects of astragalan (AG) on the expression of the neural cell adhesion molecule(NCAM) and c-fos of hippocampus CA1 region after the ischemic brain injury in rats.

METHODSOne hundred male Wistar rats (180-220 g) were divided into ten groups randomly, they were sham operated group (SOG, n = 10), three model group(MG-ld, 3d, 7d, n = 10), as well as three low and high dose astragalan treatment groups (L/H-AGTG-1d, 3d, 7d, n = 10), respectively. And then, middle cerebral artery of MG and AGTG were intercepted by operation inducing brain injured. Their cerebral blood vessel were reperfused on 1, 2, 3 d, respectively, after the L/H-AGTG were treated with the AG (5 mg/kg and 15 mg/kg, ip). After neurologic impairment(NIP) was scored, animals were decapitated to take out hippocampus for counting apoptosis , determining the expression of the NCAM and c-fos by immunohistochemistry method and RT-PCR semiquantitative analysis, respectively.

RESULTSThe NIP scores and apoptotic cell of the L-AGTG and H-AGTG were significantly lower than MG (P < 0.05 or P < 0.01). The expression of NCAM and c-fos were significantly higher than the MG (P < 0.05 or P < 0.01).

CONCLUSIONAstragalan could improve significantly neural function of ischemia brain injury in rats,the mechanism concerned probably with blocking or reversing apoptosis of hippocampus by promoting the expression of the NCAM and c-fos of hippocampus CA1 region.

Animals ; Apoptosis ; drug effects ; Astragalus membranaceus ; chemistry ; Brain Ischemia ; metabolism ; pathology ; CA1 Region, Hippocampal ; cytology ; Kaempferols ; pharmacology ; Male ; Neural Cell Adhesion Molecules ; metabolism ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Polysaccharides ; pharmacology ; Rats ; Rats, Wistar