The ameliorative effects of caffeic acid phenethyl ester in cisplatin-induced nephrotoxicity: assessment of the oxidative stress an inflammation / Los efectos de mejora del éster fenetílico del ácido cafeico en la nefrotoxicidad inducida por cisplatino: evaluación del estrés oxidativo y la inflamación

SUMMARY: The aim of this study is to determine the potential therapeutic effects of CAPE in CP-induced nephrotoxicity in rats. Cisplatin (CP) is an antineoplastic chemotherapeutic used for treatment of many cancer types but its applications may induce nephrotoxicity. Caffeic acid phenethyl ester (CAPE) is an active component of propolis and it has several important physiological activities. Rats were divided into four groups: Control, CAPE (10 µmol/kg/i.p), CP (7 mg/kg/i.p), and CP+CAPE (7 mg/kg/i.p, CP and 10 µmol/kg/i.p, CAPE). After administrations, animals were sacrificed, and kidney tissues were extracted. Histopathological changes were evaluated and TNF-α and IL-6 immunostaining were performed. Moreover, tissue SOD, CAT and MDA levels were measured by ELISA assay to assessment of oxidative stress and lipid peroxidation. CP group showed histopathological deterioration compared to the Control group and CAPE treatment attenuated this damage. When compared with Control and CAPE group, an increase in TNF-α and IL-6 immunoreactivities and tissue MDA levels were observed in the CP group while a decrease in tissue SOD and CAT levels were detected. Furthermore, an improvement was observed in the CP+CAPE compared to the CP group. We suggest that CAPE can be used as a therapeutic agent to attenuate the toxic effects of cisplatin, thanks to its antioxidant and anti-inflammatory properties.

RESUMEN: El objetivo de este estudio fue determinar los posibles efectos terapéuticos de éster fenetílico del ácido cafeico (EFAC) en la nefrotoxicidad inducida por cisplatino (CP) en ratas. El CP es un quimioterapéutico antineoplásico utilizado para el tratamiento de muchos tipos de cáncer, sin embargo sus aplicaciones pueden inducir nefrotoxicidad. El EFAC es un componente activo del propóleo y tiene varias actividades fisiológicas importantes. Para el estudio las ratas se dividieron en cuatro grupos: Control, EFAC (10 µmol / kg / ip), CP (7 mg / kg / ip) y CP + EFAC (7 mg / kg / ip, CP y 10 µmol / kg / ip, EFAC). Después de las administraciones, se sacrificaron los animales y se extrajeron los tejidos renales. Se evaluaron los cambios histopatológicos y se realizó inmunotinción de TNF-α e IL-6. Además, los niveles tisulares de SOD, CAT y MDA se midieron mediante un ensayo ELISA para evaluar el estrés oxidativo y la peroxidación lipídica. El grupo CP mostró deterioro histopatológico en comparación con el grupo Control y el tratamiento con EFAC atenuó este daño. En comparación con el grupo de control y EFAC, se observó un aumento en las inmunorreactividades de TNF-α e IL-6 y los niveles de MDA en el tejido en el grupo de CP, mientras que se detectó una disminución en los niveles de SOD y CAT en los tejidos. Además, se observó una mejora en el CP + EFAC en comparación con el grupo CP. Sugerimos que EFAC puede utilizarse como agente terapéutico para atenuar los efectos tóxicos del cisplatino, gracias a sus propiedades antioxidantes y antiinflamatorias.

A new phenylethanol glycoside from Baphicacanthis Cusiae Rhizoma et Radix / 中国中药杂志

The 95% ethanol extract of Baphicacanthis Cusiae Rhizoma et Radix was purified by multi-chromatographic methods including microporous resin, silica gel, Sephadex LH-20, and C_(18) reversed-phase column chromatography. Fourteen compounds were isolated and structurally identified, including five phenylethanoid glycosides, five phenylpropanoids, one lupinane triterpene, two alkaloids, and one flavonoid, listed as follows: 2-(4-hydroxy-3-methoxyphenyl)-3-(2-hydroxy-5-methoxyphenyl)-3-oxo-1-propanol B(1), threo-2,3-bis-(4-hydroxy-3-methoxybenzene)-3-methoxypropanol(2), 2-(3-hydroxy-4-methoxyphenyl)-ethanol-1-O-[3,4-O-di-acetyl-(1→3)-O-α-L-rhamnopyranosyl]-β-D-glucopyranoside(3), verbascoside(4), 2″,3″-di-O-acetyl martynoside(5),(+)-pinore-sinol(6), diospyrosin(7), daidzein(8), wiedemannioside B(9), buddlenol A(10), 2″-O-acetyl martyonside(11), lupeol(12), indirubin(13), and tryptanthrin(14). Compound 3 was a new phenylethanoid glycoside, and the other 10 compounds were isolated for the first time from Baphicacanthis Cusiae Rhizoma et Radix except compounds 12, 13, and 14.

Metabolic engineering of Escherichia coli for production of hydroxytyrosol / 生物工程学报

Hydroxytyrosol is an important fine chemical and is widely used in food and medicine as a natural antioxidant. Production of hydroxytyrosol through synthetic biology is of important significance. Here we cloned and functionally characterized a hydroxylase encoding gene HpaBC from Escherichia coli BL21, and both subunits of this enzyme can be successfully expressed to convert the tyrosol into hydroxytyrosol. A HpaBC gene integration expression cassette under the tac promoter was constructed, and integrated into the genome of a tyrosol hyper-producing E. coli YMG5A*R using CRISPR-Cas9 technology. Meanwhile, the pathway for production of acetic acid was deleted, resulting in a recombinant strain YMGRD1H1. Shake flask fermentation showed that strain YMGRD1H1 can directly use glucose to produce hydroxytyrosol, reaching a titer of 1.81 g/L, and nearly no by-products were detected. A titer of 2.95 g/L was achieved in a fed-batch fermentation conducted in a 5 L fermenter, which is the highest titer for the de novo synthesis of hydroxytyrosol from glucose reported to date. Production of hydroxytyrosol by engineered E. coli lays a foundation for further construction of hydroxytyrosol cell factories with industrial application potential, adding another example for microbial manufacturing of aromatic compounds.

Caffeic acid phenethyl ester protects against oxidative stress and dampens inflammation via heme oxygenase 1 / 国际口腔科学杂志·英文版

Periodontal disease is associated with chronic oxidative stress and inflammation. Caffeic acid phenethyl ester (CAPE), which is a potent inducer of heme oxygenase 1 (HO1), is a central active component of propolis, and the application of propolis improves periodontal status in diabetic patients. Here, primary murine macrophages were exposed to CAPE. Target gene expression was assessed by whole-genome microarray, RT-PCR and Western blotting. The antioxidative and anti-inflammatory activities of CAPE were examined by exposure of the cells to hydrogen peroxide, saliva and periodontal pathogens. The involvement of HO1 was investigated with the HO1 inhibitor tin protoporphyrin (SnPP) and knockout mice for Nrf2, which is a transcription factor for detoxifying enzymes. CAPE increased HO1 and other heat shock proteins in murine macrophages. A p38 MAPK inhibitor and Nrf2 knockout attenuated CAPE-induced HO1 expression in macrophages. CAPE exerted strong antioxidative activity. Additionally, CAPE reduced the inflammatory response to saliva and periodontal pathogens. Blocking HO1 decreased the antioxidative activity and attenuated the anti-inflammatory activity of CAPE. In conclusion, CAPE exerted its antioxidative effects through the Nrf2-mediated HO1 pathway and its anti-inflammatory effects through NF-κB inhibition. However, preclinical models evaluating the use of CAPE in periodontal inflammation are necessary in future studies.

Effects of caffeic acid phenethyl ester on retinal damage after traumatic brain injury / Efectos del ester fenetílico del ácido cafeico en el daño de la retina después de una lesion cerebral traumática

SUMMARY: Head trauma damages the optic nerve visual function and visual acuity.Effects of head trauma on the retina was investigated with biochemical, histological and immunohistochemical respects.The study was conducted on 30 rats with three groups: group 1 was control group (n=10). Second group was head-traumatized group (n=10) and last group was head-traumatized+Caffeic acid phenethyl ester (CAPE, i.p. 20ml/kg/day). Upon head was traumatized, CAPE was applied to trauma+CAPE group and then for the following four days. At the end of 5th day, rats were anesthetized with ketamine hydroxide and then blood samples were taken for biochemical analysis. MDA and GSH-Px values were compared. After blood sample, total eyes of rats were dissected for histopathological and immunohistochemical analysis. In trauma group, degeneration in retinal photoreceptor cells, disintegrity and in inner and outer nuclear layers, hypertrophy in ganglion cells, and hemorrhage in blood vessels were observed. In the group treated with CAPE, lesser degeneration in photoreceptor cells, regular appearances of inner and outer nuclear layers, mild hemorrhage in blood vessels of ganglionic cell layer were observed. The apoptotic changes caused by trauma seen in photoreceptor and ganglionic cells were decreased and cellular organization was preserved due to CAPE treatment. CAPE was thought to induce healing process on traumatic damages.

RESUMEN: El trauma craneal daña la función visual del nervio óptico y la agudeza visual. Se investigaron los efectos del traumatismo craneal en la retina con aspectos bioquímicos, histológicos e inmunohistoquímicos. El estudio se realizó en 30 ratas distribuidas en tres grupos: grupo control (n = 10); grupo con traumatismo craneal (n = 10); grupo con traumatismo craneoencefálico + Éster fenetílico de ácido cafeico (CAPE, i.p. 20 ml / kg / día). Sobre la cabeza traumatizada, se aplicó CAPE a trauma + grupo CAPE durante los siguientes cuatro días. Al final del día 5, las ratas se anestesiaron con hidróxido de ketamina y luego se tomaron muestras de sangre para el análisis bioquímico. Se compararon los valores de MDA y GSH-Px. Después de la muestra de sangre, se disecaron los ojos de las ratas para su análisis histopatológico e inmunohistoquímico. En el grupo de traumatismos, se observó degeneración en las células fotorreceptoras retinianas, desintegridad en capas nucleares internas y externas, hipertrofia en células ganglionares y hemorragia en los vasos sanguíneos. En el grupo tratado con CAPE, se observó una menor degeneración en las células fotorreceptoras, apariciones regulares de capas nucleares internas y externas, hemorragia leve en los vasos sanguíneos de la capa de células ganglionares. Los cambios apoptóticos causados por el trauma visto en el fotorreceptor y las células ganglionares disminuyeron y la organización celular se conservó debido al tratamiento con CAPE. Se concluyó que CAPE induce un proceso de curación en daños traumáticos.

Protective effect of caffeic acid phenethyl ester (CAPE) on ischemia­ reperfusion injury in rat ovary / Efecto protector de ester feniletílico de ácido cafeico (CAPE) en la lesión por isquemia-reperfusión en ovario de rata

The aim of this study was to investigate the effects of caffeic acid phenethyl ester (CAPE) as a prophylactic agent on ischemia/reperfusion (I/R) injury in the rat ovary. A total of 28 Wistar rats were divided into 4 equal groups: (I) sham, (II) ischemia, (III) ischemia + reperfusion, and (IV) IR + CAPE. In groups I and II, ovary torsion was not performed and no drug was administered. In group III, 1 hour of ischemia and 2 hours of reperfusion were performed and no drug was given. Ovarian tissue concentrations of malondialdehyde were significantly higher in the torsion and detorsion groups compared with the sham and Cape groups (P<0.005). The detorsion group showed preantral ovarian follicles and luteal folicules around the blood vessels and positive expression of CD34. In the CAPE group the stromal vascular endothelium with weak expression of CD34 was detected in small areas, and the ovarian follicles and the corpus luteum showed negative expression of CD34. In the study, Biochemical and histopathological results of CAPE treatment was considered to torsion-detorsioned the model showed a protective effect against tissue damage.

El objetivo de este trabajo consistió en investigar los efectos del éster fenetílico del ácido cafeico (EFAC) como agente profiláctico en la lesión por isquemia/reperfusión (I / R) en el ovario de rata. Un total de 28 ratas Wistar se dividieron en 4 grupos iguales: (I) control, (II) isquemia, (III) isquemia + reperfusión, y (IV) IR + EFAC. En los grupos I y II, no se realizó torsión ovárica y no se administró ningún fármaco. En el grupo III, se provocó una hora de isquemia, dos horas de reperfusión y no se administró ningún fármaco. Las concentraciones de malondialdehído en los tejidos ováricos fueron significativamente mayores en los grupos de torsión y de destorsión, en comparación con los grupos sham y de EFAC (P <0,005). El grupo de destorsión mostró folículos ováricos preantrales y folículos lúteos alrededor de los vasos sanguíneos y expresión positiva de CD34. En el grupo EFAC el endotelio vascular estromal con expresión débil de CD34 se detectó en áreas pequeñas, y los folículos ováricos y el cuerpo lúteo mostraron expresión negativa de CD34. En el estudio, fueron considerados los resultados bioquímicos e histopatológicos del tratamiento EFAC en relación a la torsión-destorsión, desarrollando un modelo que mostró un efecto protector contra el daño tisular.

Terpinen-4-ol, tyrosol, and ß-lapachone as potential antifungals against dimorphic fungi

Abstract This study aimed to evaluate the in vitro antifungal activity of terpinen-4-ol, tyrosol, and β-lapachone against strains of Coccidioides posadasii in filamentous phase (n = 22) and Histoplasma capsulatum in both filamentous (n = 40) and yeast phases (n = 13), using the broth dilution methods as described by the Clinical and Laboratory Standards Institute, to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of these compounds. The mechanisms of action of these compounds were also investigated by analyzing their effect on cell membrane permeability and ergosterol synthesis. The MIC and MFCf these compounds against C. posadasii, mycelial H. capsulatum, and yeast-like H. capsulatum, were in the following ranges: 350-5720 µg/mL, 20-2860 µg/mL, and 40-1420 µg/mL, respectively for terpinen-4-ol; 250-4000 µg/mL, 30-2000 µg/mL, and 10-1000 µg/mL, respectively, for tyrosol; and 0.48-7.8 µg/mL, 0.25-16 µg/mL, and 0.125-4 µg/mL, respectively for β-lapachone. These compounds showed a decrease in MIC when the samples were subjected to osmotic stress, suggesting that the compounds acted on the fungal membrane. All the compounds were able to reduce the ergosterol content of the fungal strains. Finally, tyrosol was able to cause a leakage of intracellular molecules.

Influence of Tyrosol on Cell Growth Inhibition of KB Human Oral Cancer Cells

Tyrosol, a phenylethanoid and a derivative of phenethyl alcohol, possesses various biological properties, such as anti-oxidative and cardioprotective activity. Olive oil is the principal source of tyrosol in the human diet. However, so far the anti-cancer activity of tyrosol has not yet been well defined. This study therefore undertakes to examine the cytotoxic activity and the mechanism of cell death exhibited by tyrosol in KB human oral cancer cells. Treatment of KB cells with tyrosol induced the cell growth inhibition in a concentration- and a time-dependent manner. Furthermore, the treatment of tyrosol induced nuclear condensation and fragmentation of KB cells. Tyrosol also promoted proteolytic cleavage of procaspase-3, -7, -8 and -9, increasing the amounts of cleaved caspase-3, -7, -8 and -9. In addition, tyrosol increased the levels of cleaved PARP in KB cells. These results suggest that tyrosol induces the suppression of cell growth and cell apoptosis in KB human oral cancer cells, and is therefore a potential candidate for anti-cancer drug discovery.

Activation of NF-κB and AP-1 Mediates Hyperproliferation by Inducing β-Catenin and c-Myc in Helicobacter pylori-Infected Gastric Epithelial Cells

PURPOSE: In the gastric mucosa of Helicobacter pylori (H. pylori)-infected patients with gastritis or adenocarcinoma, proliferation of gastric epithelial cells is increased. Hyperproliferation is related to induction of oncogenes, such as β-catenin and c-myc. Even though transcription factors NF-κB and AP-1 are activated in H. pylori-infected cells, whether NF-κB or AP-1 regulates the expression of β-catenein or c-myc in H. pylori-infected cells has not been clarified. The present study was undertaken to investigate whether H. pylori-induced activation of NF-κB and AP-1 mediates the expression of oncogenes and hyperproliferation of gastric epithelial cells. MATERIALS AND METHODS: Gastric epithelial AGS cells were transiently transfected with mutant genes for IκBα (MAD3) and c-Jun (TAM67) or treated with a specific NF-κB inhibitor caffeic acid phenethyl ester (CAPE) or a selective AP-1 inhibitor SR-11302 to suppress activation of NF-κB or AP-1, respecively. As reference cells, the control vector pcDNA was transfected to the cells. Wild-type cells or transfected cells were cultured with or without H. pylori. RESULTS: H. pylori induced activation of NF-κB and AP-1, cell proliferation, and expression of oncogenes (β-catenein, c-myc) in AGS cells, which was inhibited by transfection of MAD3 and TAM67. Wild-type cells and the cells transfected with pcDNA showed similar activities of NF-κB and AP-1, proliferation, and oncogene expression regardless of treatment with H. pylori. Both CAPE and SR-11302 inhibited cell proliferation and expression of oncogenes in H. pylori-infected cells. CONCLUSION: H. pylori-induced activation of NF-κB and AP-1 regulates transcription of oncogenes and mediates hyperproliferation in gastric epithelial cells.

Advances in biosynthesis of 2-phenylethanol by yeasts / 生物工程学报

2-Phenylethanol (2-PE) is an aromatic alcohol with a pleasant rose-like fragrance. It has been widely used in food, cosmetic, and pharmaceutical industry. Most of 2-PE is produced by chemical synthesis, but the use of chemically synthesized product is restricted in some fields. 2-PE from plant extraction is natural but its production is very low. Microbial biotransformation is a promising process to produce natural 2-PE. In this paper, we review recent research progress in the synthetic metabolic pathways and regulatory processes of 2-PE in yeast, and strategies for improving 2-PE production. Moreover, we discuss the limitation of current progress and future research directions.

Effects of aroma quality on the biotransformation of natural 2-phenylethanol produced using ascorbic acid

Background Natural 2-phenylethanol (2-PE) is an important flavoring that emits the aroma of roses. During biotransformation, the aroma quality of natural 2-PE is affected by its main by-products, which include butanol, isobutyric acid, butyric acid, and isovaleric acid. Thus, controlling undesirable by-product formation can reduce the effect of odor on 2-PE aroma quality. Results 2-PE was produced through biotransformation using l-phenylalanine as a substrate and glucose as a carbon source. Ascorbic acid was added to the system to improve the redox reaction and suppress the generation of by-products. Principal component analysis of the aroma quality of 2-PE was performed using an electronic nose. Similarity analysis revealed that the effects of four by-products on 2-PE aroma quality may be ranked in the following order: isovaleric acid > butyric acid > isobutyric acid > butanol. The sample that exhibited the best similarity to the standard 2-PE sample (99.19%) was the sample to which ascorbic acid had been added during glucose metabolism. Conclusions 2-PE produced through the addition of ascorbic acid exhibited the closest aroma similarity to the standard 2-PE sample.

Phenylpropanoids and phenylethanol from flowers of Rosa rugosa / 中国中药杂志

A new phenylpropanoid (1), together with seven known ones (2-8), has been isolated from the flowers of Rosa rugosa collected from Shanxi province by using various chromatographic techniques. Compound 1 is a new compound, and it displayed cytotoxicity against NB4, SH-SY5Y, PC3, A549 and MCF7 cell lines with IC₅₀ values of 8.2, 6.2, 4.3, 2.8, and 9.6 µmol · L⁻¹ respectively.

Optimization of extraction technology for salidroside, tyrosol, crenulatin and gallic acid in Rhodiolae Crenulatae Radix et Rhizoma with orthogonal test / 中国中药杂志

The extracting technology of salidroside, tyrosol, crenulatin and gallic acid from Rhodiolae Crenulatae Radix et Rhizoma was optimized. With extraction rate of salidroside, tyrosol, crenulatin and gallic acid as indexes, orthogonal test was used to evaluate effect of 4 factors on extracting technology, including concentration of solvent, the dosage of solvent, duration of extraction, and frequency of extraction. The results showed that, the best extracting technology was to extract in 70% alcohol with 8 times the weight of herbal medicine for 2 times, with 3 hours once. High extraction rate of salidroside, tyrosol, crenulatin and gallic acid were obtained with the present technology. The extracting technology was stable and feasible with high extraction rate of four compounds from Rhodiolae Crenulatae Radix et Rhizoma, it was suitable for industrial production.

Effect of andrographolide on quorum sensing and relevant virulence genes of Candida albicans / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effect of andrographolide (AG) on quroum sensing (QS) and relevant virulence genes of Candida albicans.</p><p><b>METHOD</b>Gas-chromatography-mass spectrometry (GC-MS) was applied to detect the changes in the content of farnesol and tyrosol in C. albicans intervened by AG. The real-time quantitative PCR (qRT-PCR) was adopted to inspect the expressions of relevant virulence genes such as CHK1, PBS2 and HOG1 regulated by QS.</p><p><b>RESULT</b>At 2 h after the growth of C. albican, the farnesol and tyrosol secretions reduced, without notable change after intervention with AG. The secretions were highest at 12 h and decreased at 24 h. After the intervention with different concentrations of AG, the farnesol content reduces, whereas tyrosol increased, indicating a dose-dependence, particularly with 1 000 mg x L(-1) AG. qRT-PCR revealed that 1 000 mg x L(-1) AG could down-regulate CHK1 by 2.375, 3.330 and 4.043 times and PBS2 by 2.010, 4.210 and 4.760 times, with no significant change in HOG1.</p><p><b>CONCLUSION</b>AG could inhibit the farnesol secretion, promote the tyrosol secretion and down-regulate QS-related virulence genes CHK1 and PBS2 expressions.</p>

Simultaneously preparation of grams of high purity tyrosol, crenulatin and salidroside from Rhodiola crenulata / 中国中药杂志

Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.

Anti-catabolic effect of caffeic acid phenethyl ester, an active component of honeybee propolis on bone loss in ovariectomized mice: a micro-computed tomography study and histological analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Osteoporosis (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.</p><p><b>METHODS</b>Eighteen 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.</p><p><b>RESULTS</b>Bone 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).</p><p><b>CONCLUSION</b>CAPE therapy results in the protection of bone loss induced by OVX.</p>

Increase of TNFα-stimulated osteoarthritic chondrocytes apoptosis and decrease of matrix metalloproteinases 9 by NF-κB inhibition / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).</p><p><b>METHODS</b>Annexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.</p><p><b>RESULTS</b>It was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.</p><p><b>CONCLUSION</b>NF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.</p>

Impact of NF-kappaB inhibitor on STAT3 translocation in PC-3 prostate cancer cell line / 中华男科学杂志

<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>PC-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.</p><p><b>RESULTS</b>After 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).</p><p><b>CONCLUSION</b>CAPE 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.</p>

Phenylethanoid glycosides distribution in medicinal plants of Gesneriaceae / 中国中药杂志

To investigate the role of distribution and phylogeny of phenylethanoid glycoside in medicinal plants of Gesneriaceae, five phenylpropanoid glycosides, acteoside, paraboside B, isonuomioside A, paraboside II, and paraboside III were quantitatively determined in 12 species of Gesneriaceae by HPLC. The existence and content of these compounds were analyzed. The results showed that phenylethanoid glycosides were found in the most of those plants, but the kind of phenylethanoid glycosides varied in different species. Acteoside distribute in most of this plant group, paraboside B, isonuomioside A, paraboside II, and paraboside III were rare in those plants. The results of this study support morphological viewpoint that Trib. Trichosporeae is more developmental than Trib. Didymocarpeae.

Salidroside biosynthesis pathway: the initial reaction and glycosylation of tyrosol / 生物工程学报

Salidroside, the 8-O-beta-D-glucoside of tyrosol, is a novel adaptogenic drug extracted from the medicinal plant Rhodiola sachalinensis A. Bor. Due to the scarcity of R. sachalinensis and its low yield of salidroside, there is great interest in enhancing the production of salidroside by biotechnological process. Glucosylation of tyrosol is thought to be the final step in salidroside biosynthesis. In our related works, three UGT clones were isolated from the roots and the cultured cells. Our intention was to combine the catalytic specificity of these UGTs in vitro in order to change the level of salidroside in vivo by over-expression of the above UGTs. However, as the aglycone substrate of salidroside, the biosynthetic pathway of tyrosol and its regulation are less well understood. The results of related studies revealed that there are two different possibilities for the tyrosol biosynthetic pathway. One possibility is that tyrosol is produced from a p-coumaric acid precursor, which is derived mainly from phenylalanine. The second possibility is that the precursor of tyrosol might be tyramine, which is synthesized from tyrosine. Our previous work demonstrated that over-expression of the endogenous phenylalanine ammonia-lyase gene (PALrs1) and accumulation of p-coumaric acid did not facilitate tyrosol biosynthesis. In contrast, the data presented in our recent work provide in vitro and in vivo evidence that the tyrosine decarboxylase (RsTyrDC) is most likely to have an important function in the initial reaction of the salidroside biosynthesis pathway in R. Sachalinensis.