OBJECTIVETo explore potency material bases of Xuebijing (XBJ) formula, and to analyze its effects at the molecular network level.

METHODSTotally 16 sepsis-related targets were selected and classified into three categories such as inflammation, immune, and coagulation referring to biological roles. Then molecular database of chemical compositions in XBJ formula were constructed to explore mutual actions with inflammation, immune, and coagulation targets.

RESULTSDanshen root and safflower, with more effector molecules with immune and coagulation targets, have extensive anticoagulation and anti-inflammation effects. The former 10 molecules with better mutual actions with sepsis targets were sequenced as tryptophane, danshensu, gallic acid, salvianolic acid D, protocatechuic acid, salvianolic acid A, danshensu C, vanillic acid, rosmarinic acid, phenylalanine. There existed two phenomena in XBJ formula as follows. One component had stronger actions with multi-targets, for example, danshensu had actions with 13 targets. Meanwhile, different components acted on the same target protein, for example, 8 molecules acted with MD-2.

CONCLUSIONXBJ formula had certain potential synergistic effects with sepsis targets, which could provide certain referential roles for findina new type anti-septic drugs.

Caffeic Acids ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Gallic Acid ; Hydroxybenzoates ; Inflammation ; Lactates ; Sepsis ; drug therapy

OBJECTIVETo assess and compare the in vitro anti-oxidative activities among Siwu Decoction Serial Recipes, their composed crude herbs, and main aromatic acids they contained.

METHODSTheir anti-oxidative activities (including Siwu Decoction and correlated recipes such as Taohong Siwu Decoction, Xiangfu Siwu Decoction, Shaofu Zhuyu Decoction, and Xiongqiong Decoction, 16 kinds of crude herbs, and main aromatic acids they contained) were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical clearance method.

RESULTSThe selected five decoctions showed obvious activities of scavenging free radicals. Siwu Decoction was better than other decoctions in scavenging free radicals and Xiongqiong Decoction was the least. Among the 16 kinds of crude herbs, red peony root, white peony root, safflower, ligustici chuanxiong, common aucklandia root showed the strongest activities, while peach seed showed the poorest activities. Among aromatic acids, gallic acid, protocatechuic acid, vanillic acid, caffeic acid, chlorogenic acid, p-coumaric acid, and ferulic acid showed obvious anti-oxidative activities in scavenging free radicals, showing obvious dose-effect correlation. p-hydroxybenzoic acid, benzoic acid, and cinnamic acid showed no activities on scavenging free radicals (P > 0.05).

CONCLUSIONSiwu Decoction and aromatic acids contained in correlated decoctions played significant roles in anti-oxidative activities.

Antioxidants ; pharmacology ; Biphenyl Compounds ; Caffeic Acids ; pharmacology ; Chlorogenic Acid ; pharmacology ; Coumaric Acids ; pharmacology ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Free Radicals ; metabolism ; Gallic Acid ; pharmacology ; Hydroxybenzoates ; pharmacology ; Picrates

BACKGROUNDOsteoporosis (OP) is a common bone disease, which adversely affects life quality. Effective treatments are necessary to combat both the loss and fracture of bone. Recent studies indicated that caffeic acid phenethyl ester (CAPE) is a natural chemical compound from honeybee propolis which is capable of attenuating osteoclastogenesis and bone resorption. Therefore, this study aimed to investigate the effect of CAPE on bone loss in OP mice using micro-computed tomography (CT) and histology.

METHODSEighteen mice were prepared and evenly divided into three groups. The six mice in the sham+PBS group did not undergo ovariectomy and were intraperitoneally injected with PBS during the curing period. Twelve mice were ovariectomized (OVX) to induce OP. Six of them in the OVX+CAPE group were intraperitoneally injected with 0.5 mg/kg CAPE twice per week for 4 weeks after ovariectomy. The other six OVX mice in OVX+PBS group were treated with PBS. All the mice were sacrificed 4 weeks after ovariectomy. The tibias were bilaterally excised for micro-CT scan and histological analysis. The Mann-Whitney U test was used to test the statistical differences among groups.

RESULTSBone loss occurred in OVX mice. Compared with the sham+PBS group, mice in the OVX+PBS group exhibited a significant decrease in bone mineral density (BMD, P < 0.05), bone volume fraction (BV/TV, P < 0.01), trabecular thickness (Tb.Th, P < 0.05), and trabecular number (Tb.N, P < 0.01), as well as a non-insignificant increase in the number of osteoclasts (N.Oc/B.Pm). With CAPE treatment, the microarchitecture of the tibial metaphyses was significantly improved with a reduction of osteoclast formation. Compared with the OVX+PBS group, BV/TV in the OVX+CAPE group was significantly increased by 33.9% (P < 0.05).

CONCLUSIONCAPE therapy results in the protection of bone loss induced by OVX.

Animals ; Bone Density ; drug effects ; Caffeic Acids ; pharmacology ; Female ; Metabolism ; drug effects ; Mice ; Mice, Inbred C57BL ; Ovariectomy ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; Propolis ; chemistry ; Tomography, X-Ray Computed

AIMOxidized low-density lipoprotein (LDL) is involved in the development of atherosclerosis. Oxidative modulation of serum LDL is related to oxygen free radicals. Antioxidants have beneficial effects on oxidative modulation of LDL and development of atherosclerosis. Salvia miltriorhiza (Danshen) preparations have been widely used in the treatment of cardio-cerebral vascular diseases in China. Salvianolic acid A (Sal-A), one of the components of Salvia miltriorhiza, was shown to have strong antioxidative activity. The aim of this investigation was to evaluate the effect of Sal-A on human LDL oxidative modulation mediated by copper ions.

METHODSOxidation of human LDL was performed in pH 7.4 phosphate-buffered saline with 10 mumol.L-1 CuSO4 at 37 degrees C water for 20 h. The content of malondialdehyde (MDA), lipofuscin and vitamin E in LDL as well as the rate of electrophoretic mobility (REM) of LDL were measured. The generation of free radicals during LDL oxidation was detected by low level-chemiluminescence (LL-CL). The chelation of Cu2+ by Sal-A was detected by UV-spectrum scanning.

RESULTSSal-A (10(-6) to 10(-4) mol.L-1) was shown to markedly reduce the production of MDA and lipofuscin as well as the consumption of vitamin E during LDL oxidation. Sal-A (10(-4) mol.L-1) was also shown to inhibit the increase of REM of LDL caused by oxidative modification. In addition, the spectrum of LL-CL showed that Sal-A (10(-6) to 10(-5) mol.L-1) decreased the generation of free radicals during LDL oxidation in a dose dependent manner. The differential UV-spectrum of Sal-A in the presence of Cu2+ indicated that Sal-A could chelate copper ions.

CONCLUSIONSal-A has inhibitory effect on Cu2+ mediated human LDL oxidation through chelating Cu2+ and scavenging free radicals.

Antioxidants ; pharmacology ; Caffeic Acids ; pharmacology ; Copper ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Free Radical Scavengers ; pharmacology ; Humans ; Lactates ; pharmacology ; Lipofuscin ; metabolism ; Lipoproteins, LDL ; metabolism ; Malondialdehyde ; metabolism ; Oxidation-Reduction ; drug effects ; Vitamin E ; metabolism

In this study, the "150-cavity", next to the H5N1 influenza virus neuraminidase activity site, has been used as the target to design and synthesize a structural analogue of chlorogenic acid, N-caffeoyl-GABA, using the flexible docking simulation. The docking study showed that the N-caffeoyl-GABA could be inserted into the "150-cavity" and combined with the Arg156 side chain by hydrogen bond. The best binding free energy of H5N1 NA-N-caffeoyl-GABA complex was -7.70 kcal mol(-1), equivalent that of the NA-oseltamivir. At the same time, using the H5N1 pseudotyping virus-based NA inhibitors screening model, we determined the inhibitory effect of oseltamivir, chlorogenic acid and N-caffeoyl-GABA on the NA. Compared with chlorogenic acid, N-caffeoyl-GABA significantly enhanced the inhibitory effect on NA, but less than oseltamivir. This study showed that the "150-cavity" could possibly be used as a new neuraminidase inhibitors target, and provided a path for the development of new neuraminidase inhibitors.
Antiviral Agents ; chemical synthesis ; pharmacology ; Caffeic Acids ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; pharmacology ; HEK293 Cells ; Humans ; Influenza A Virus, H5N1 Subtype ; enzymology ; Neuraminidase ; antagonists & inhibitors ; metabolism ; gamma-Aminobutyric Acid ; analogs & derivatives ; chemical synthesis ; pharmacology

OBJECTIVETo study the constituents with the pain-relieving activity from the stem rind of Daphne giraldii.

METHODThe partition of the ethanol extract and chromatographic separation of the fractions were carried out by the monitoring of anelgesic pharmacological activity. The structures of the isolated compounds were determined by MS and NMR.

RESULTFour compounds were isolated from the pain-relieving fraction. Three of them were identified as diterpenes, gniditrin (1), gnidicin (2) and daphnetoxin (3). Compound 4 was determined as Z-octadecyl caffeate.

CONCLUSIONCompounds 1, 2 and 4 were isolated from the plant for the first time.

Analgesics ; chemistry ; isolation & purification ; pharmacology ; Caffeic Acids ; chemistry ; isolation & purification ; pharmacology ; Daphne ; chemistry ; Diterpenes ; chemistry ; isolation & purification ; pharmacology ; Heterocyclic Compounds, 4 or More Rings ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

OBJECTIVEMicroRNAs (miRNAs) play important roles in cell proliferation, differentiation and apoptosis. 1, 3, 4-tri-O-galloyl-6-O-caffeoyl-β-D-glucopyranose (BJA32515) is a new natural ellagitannin compound extracted from Balanophora Japonica MAKINO. The effect of BJA32515 on the expression of miRNAs in cancer cells has not yet been explored. Objective The present study was carried out to examine the changes in miRNA expression profiles in human HepG(2) hepatocarcinoma cells following BJA32515 exposure.

METHODSThe proliferation of BJA32515-exposed HepG(2) cells was assessed using a colorimetric assay (cell counting kit-8). The miRNA expression profile of the cancer cells was analyzed using a miRNA array and quantitative real-time PCR. Apoptosis was assessed by annexin V and propidium iodide staining.

RESULTSBJA32515 inhibited the cell proliferation and increased apoptosis in HepG(2) cancer cells. The exposure to BJA32515 also caused alterations in the miRNA expression profile in the cells, with 33 miRNAs upregulated and 59 down-regulated. The up-regulation of let-7a and miR-29a and the down-regulation of miR-373 and miR-197 were verified by quantitative real-time PCR. CONCLSION: BJA32515-modifed miRNA expression may mediate the antiproliferative effect of this compound in HepG(2) cancer cells.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Balanophoraceae ; chemistry ; Caffeic Acids ; isolation & purification ; pharmacology ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glucosides ; isolation & purification ; pharmacology ; Hep G2 Cells ; Humans ; Hydrolyzable Tannins ; isolation & purification ; pharmacology ; MicroRNAs ; genetics ; metabolism ; Polyphenols

OBJECTIVETo investigate the effects of salvianolic acids on human umbilical vein endothelial cells (HUVEC) against damage induced by cholestane-3beta-5alpha-6beta-triol (chol-triol).

METHODSThe viability of HUVEC was measured by MTT method. The apoptosis of HUVEC induced by chol-triol was detected by flow cytometry and TUNEL assay. The production of malondialdehyd (MDA) in HUVEC was tested by thiobarbaturic acid (TBA) assay.

RESULTSThe viability of HUVEC treated with chol-triol 100 micro mol/L decreased by 39.8% while salvianolic acids 100 micro g/ml increased by 27.9%. The apoptotic rate of HUVEC measured by PI staining increased from 6% - 8% to 17% - 20% after chol-triol treatment for 12 h. Salvianolic acids 100 micro g/ml reduced the apoptotic rate to 10% - 14% after treatment HUVEC for 1 h prior to chol-triol treatment. In another experiment, chol-triol increased the number of TUNEL-positive cells 5 times, but salvianolic acids 10 micro g/ml and 100 micro g/ml reduced the number of TUNEL-positive cells by 36.9% and 61.2%, respectively. The production of MDA in HUVEC increased by 120.7% after chol-triol treatment for 12 h. Salvianolic acids 10 micro g/ml and 100 micro g/ml also decreased the concentration of MDA by 28.7% and 39.8%, respectively.

CONCLUSIONSalvianolic acids has protective effect on endothelial cells against damage induced by chol-triol.

Apoptosis ; drug effects ; Benzofurans ; pharmacology ; Caffeic Acids ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Cholestanols ; toxicity ; Cinnamates ; pharmacology ; Depsides ; Endothelium, Vascular ; cytology ; drug effects ; Humans ; Lactates ; pharmacology ; Malondialdehyde ; 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 observe the changes in the expressions of STAT3 and NF-KB in PC-3 cells after IL-6 stimulation and to verify the effects of the NF-KB inhibitor caffeic acid phenethyl ester (CAPE) on the expressions of p-STAT3 and IL-6 in the PC-3 prostate cancer cell line.

METHODSPC-3 prostate cancer cells were treated with IL-6 at 20 ng/ml for 5, 10, 20, 30 and 45 min. The protein and mRNA expressions of STAT3 and NF-kappaB were measured by Western blot and real time PCR, respectively, and the cell cycle was detected by flow cytometry. The PC-3 cells were exposed to TNF-alpha or TNF-alpha + CAPE, followed by determination of the IL-6 expression in the supernatant of the cells by ELISA and the expression of p-STAT3 by Western blot.

RESULTSAfter IL-6 stimulation, both the expression of p-STAT3 protein and the proliferation index of the PC-3 cells were significantly increased, and so were the expressions of IL-6 and p-STAT3 protein in the supernatant after TNF-alpha treatment (P < 0.05). TNF-alpha + CAPE induced statistically lower expressions of IL-6 and p-STAT3 than TNF-alpha alone (P < 0.05).

CONCLUSIONCAPE can inhibit IL-6 secretion induced by TNF-alpha in PC-3 cells and thus suppress STAT3 translocation. Therefore, by inhibiting the expression of NF-kappaB and affecting STAT3 and other related cell signaling pathways, CAPE may become a new therapeutic option for prostate cancer.

Caffeic Acids ; pharmacology ; Cell Line, Tumor ; Humans ; Interleukin-6 ; metabolism ; pharmacology ; Male ; NF-kappa B ; antagonists & inhibitors ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; drug effects ; Tumor Necrosis Factor-alpha ; pharmacology