Biomedical subjects
Publications and source records attributed to C T Ho.
A new iridoid glucoside (1), named citrifolinoside A, was isolated from the leaves of Morinda citrifolia along with the known iridoids asperuloside and asperulosidic acid. The structure of 1 was established by interpretation and full assignments of NMR spectroscopic data.
An investigation on the gum exudates of Commiphora myrrha has led to the isolation of six sesquiterpenoids. On the basis of spectroscopic data interpretation, they were determined as two new furanosesquiterpenoids, rel-1S,2S-epoxy-4R-furanogermacr-10(15)-en-6-one (1) and rel-2R-methyl-5S-acetoxy-4R-furanogermacr-1(10)Z-en-6-one (2), and four known furanosesquiterpenoids, rel-3R-methoxy-4S-furanogermacra-1E,10(15)-dien-6-one (3), rel-2R-methoxy-4R-furanogermacr-1(10)E-en-6-one (4), furanogermacra-1(10)Z,4Z-dien-6-one, and curzerenone [6,7-dihydro-5beta-isopropenyl-3,6beta-dimethyl-6-vinylbenzofuran-4(5H)-one]. This is the first report of the relative stereochemistry for the known compounds 3 and 4. Compound 1 exhibited weak cytotoxic activity against a MCF-7 breast tumor cell line in a clonogenic assay, while the other five compounds were inactive in this assay.
Low level laser therapy has been used in treating many conditions with reports of multiple clinical effects including promotion of healing of both hard and soft tissue lesions. Low level laser therapy as a treatment modality remains controversial, however. The effects of wavelength, beam type, energy output, energy level, energy intensity, and exposure regime of low level laser therapy remain unexplained. Moreover, no specific therapeutic window for dosimetry and mechanism of action has been determined at the level of individual cell types. The aim of this study was to investigate the effects of low level laser irradiation on the human osteosarcoma cell line, SAOS-2. The cells were irradiated as a single or daily dose for up to 10 days with a GaAlAs continuous wave diode laser (830 nm, net output of 90 mW, energy levels of 0.3, 0.5, 1, 2, and 4 Joules). Cell viability was not affected by laser irradiation, with the viability being greater than 90% for all experimental groups. Cellular proliferation or activation was not found to be significantly affected by any of the energy levels and varying exposure regimes investigated. Low level laser irradiation did result in a heat shock response at an energy level of 2 J. No significant early or late effects of laser irradiation on protein expression and alkaline phosphatase activity were found. Investigation of intracellular calcium concentration revealed a tendency of a transient positive change after irradiation. Low level laser irradiation was unable to stimulate the osteosarcoma cells utilised for this research at a gross cell population level. The heat shock response and increased intracellular calcium indicate that the cells do respond to low level laser irradiation. Further research is required, utilising different cell and animal models, to more specifically determine the effects of low level laser irradiation at a cellular level. These effects should be more thoroughly investigated before low level laser therapy can be considered as a potential accelerator stimulus for orthodontic tooth movement.
Post-curing treatments have been known to improve the mechanical stability of visible light-cured composites. After individual post-curing treatment, the flexural strength (FS) of four commercial direct/indirect placement composite materials which differ greatly in composition [oligocarbonate dimethacrylate (OCDMA)-based Conquest C & B (CQT), Bisphenol-A glycidyl dimethacrylate (BisGMA)-based Charisma, urethane dimethacrylate (UDMA)-based Concept (CCT), and BisGMA/UDMA-based Dentacolor] was evaluated under water in the temperature range of 12-50 degrees C. A control series was tested in air at room temperature (25 +/- 1 degrees C). Data were analysed using ANOVA and Duncan's test. Flexural strengths overall decreased (20-40%, P < 0.01) with increasing temperatures except with Conquest C & B. Surprisingly, higher FS values were found in wet conditions than in dry conditions at 25 degrees C. UDMA-based materials much more easily undergo softening in water and by temperature change than do BisGMA- or OCDMA-based materials. Post-cured composites can be significantly affected by exposure to oral environments. Different composition determines the degree of influence.
Cyclophosphamide (CYC) has proven beneficial in preserving renal function in patients with lupus with diffuse proliferative glomerulonephritis (DPGN). However, the optimal route of CYC administration is unknown because direct comparative studies are unavailable. In this open study, we compared the renal outcome of two historical cohorts of patients with diffuse proliferative lupus nephritis (World Health Organization classes IVa and IVb) treated with either intravenous (IV) pulse CYC (group A; n = 22) or sequential oral CYC followed by azathioprine (AZA; group B; n = 21) and followed up prospectively. Both groups of patients had similar clinical, biochemical, and renal parameters at baseline. At 24 months posttreatment, significant improvements in proteinuria, creatinine clearance, serum albumin level, and lupus serological results were evident in both groups. Compared with patients in group A, patients in group B had more complete or partial remission (90% versus 73%) and less risk for treatment failure (5% versus 14%), renal flares (5% versus 14%), and doubling of creatinine levels (5% versus 9%), but the difference was not statistically significant. However, patients treated with oral immunosuppression had an insignificant increase in rates of herpes zoster infection (19% versus 9%) and menstrual disturbance (50% versus 29%). We conclude that sequential oral immunosuppression with CYC and AZA tended to have better efficacy than IV pulse CYC in the treatment of lupus DPGN but was associated with more toxicities. Additional randomized trials involving a larger cohort of patients with a longer period of observation are necessary.
The possible beneficial effects of tea consumption have attracted a great deal of attention. Many of the biological effects have been attributed to tea catechins, but the metabolic fate of these compounds is not clear. In the present study, a major metabolite observed in human blood and urine samples after green tea administration was identified as a O-methylated derivative of (-)-epigallocatechin (EGC) by comparison with products from chemical and enzymatic O-methylation of EGC. The structure of this metabolite was elucidated as 4'-O-methyl-(-)-epigallocatechin (4'-O-MeEGC) by (1)H and (13)C NMR and heteronuclear multiple bond connectivity experiment. The human plasma level of 4'-O-MeEGC reached its peak value within the first 2 h following tea ingestion. Its maximum concentration was 4 to 6 times higher than that of EGC. The half-lives of EGC and 4'-O-MeEGC in the blood were 1.02 +/- 0.07 and 4.39 +/- 1.14 h, respectively. The amount of 4'-O-MeEGC excreted in urine was about 3 times higher than that of EGC, and 88% of 4'-O-MeEGC was excreted in urine within 8 h. The present structural information and concentration-time profile of this metabolite provide the basis for understanding the biotransformation of EGC and for future elucidation of its biological activities.
Dietary factors play important roles in the carcinogenic process. The results of epidemiological data and some laboratory animal studies indicate that certain naturally occurring and synthetic components are able to block the carcinogenic process and inhibit the development of certain cancers. Dibenzoylmethane (DBM), a curcumin-related beta-diketone analogue has been reported to exhibit a remarkable inhibitory effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumorigenesis in Sencar mice. The present study investigated the possible mechanisms of inhibitory action of DBM on DMBA-induced mammary tumorigenesis in mice. The summarized results indicate that: (1) in in-vitro studies. DBM inhibited DMBA metabolism and the formation of DMBA-DNA adducts in a dose-dependent manner; (2) in the assay of competitive binding to estrogen receptors with [3H]-estradiol in vitro, DBM showed weak binding affinity; (3) in vivo, feeding of 1% DBM in the diet of immature Sencar mice for 4 -5 weeks decreased the uterine and parametrial fat pad weights, and lowered the serum estrogen and triglyceride levels. This study provides insight into the mechanisms involved in the inhibitory action of DBM in mouse mammary tumorigenesis.
Theaflavin (TF-1), theaflavin-3-monogallate and theaflavin-3'-monogallate mixture (TF-2), and theaflavin-3,3'-digallate (TF-3) are the major black tea polyphenols. Here we compared the effects of these polyphenols on cell growth, apoptosis, and gene expression in normal and cancerous cells. We showed that TF-2 (10-50 microM) inhibited the growth of SV40 transformed WI38 human cells (WI38VA) and Caco-2 colon cancer cells but had little effect on the growth of their normal counterparts. The IC50s of TF-2 for the growth inhibition of WI38 and WI38VA cells were, respectively, 300 and 3 microM. The other two black tea polyphenols, TF-1 and TF-3, did not exhibit such differential growth-inhibitory effect. TF-2, but not TF-1 or TF-3, induced apoptosis in transformed WI38VA cells but not in normal WI38 cells, suggesting that apoptosis was responsible, at least in part, for the differential growth-inhibitory effect of TF-2. Cox-2 has been implicated in intestinal carcinogenesis. Among the tea polyphenols tested, TF-2 and, to a lesser degree, (-)-epigallocatechin gallate inhibited cyclooxygenase (Cox)-2 gene expression. TF-2 at 50 microM completely blocked the serum-induced Cox-2 gene expression at both mRNA and protein level. Other genes, including c-fos, c-myc, thymidine kinase, proliferating cell nuclear antigen, BRCA1, BRCA2, and Cox-1, were not significantly affected by TF-2. These findings suggest that TF-2 may be responsible, at least in part, for the chemopreventive activity in black tea extracts.
This study investigated the effect of pressure on the retention behavior of a model protein, lysozyme, on octadecylsilica (C18) stationary phase under various equilibrium conditions. It is demonstrated that the retention time of the lysozyme was increased by as much as two to three times as the absolute pressure on the viewing window was increased from 23 to 318 bar. This pressure-induced retention was likely to be reversible and the corresponding volume change (deltaV = Vsta - Vmob) was found to be on the order of minus tens to hundreds of mL/mol. Moreover, the pressure-induced retention was also observed for a homologous series of hydrophobic poly-L-phenylalanine, which do not have the secondary structure, and the volume change was determined to be around minus 10 mL/mol per phenylalanine. Perturbations in solute ionization and conformational change are predicted to have a minor impact under the investigated conditions. It is believed that the pressure-induced shift of the equilibria regarding hydrophobic ad-desorption is the major cause of the observed increase of protein retention. About ten phenylalanine-equivalent residues on the lysozyme surface were involved in the hydrophobic association with the chromatographic ligands.
We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.
Rosemary and sage are common spices used in food. In our recent search of cancer chemopreventive agents from spices, the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids. Here we discuss chromatographic methods used to separate and purify compounds from these spices and MS and NMR spectrometry to identify the isolated compounds. Several new compounds isolated from sage were determined to be 6-O-caffeoyl-beta-D-fructofuranosyl-(2-->1)-beta-glucopyranoside, 1-O-caffeoyl-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside, 1-O-p-hydroxybenzoyl-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside, 1-O-(3-methyl-2,3,4-trihydroxybutyl)-6-O-feruloyl-beta-D-glucopyranoside, 4-hydroxyacetophenone 4-O-[5-O-(3,5-dimethoxy-4-hydroxybenzoyl)-beta-D-apiofrunosyl]-(1-->2)-beta-D-glucopyranoside and 1-O-[2-hydroxy-5-(2-hydroxyethyl)phenyl]-6-O-trans-caffeoyl-beta-D-glucopyranoside.
Boswellin (BE), a methanol extract of the gum resin exudate of Boswellia serrata, contains naturally occurring triterpenoids, beta-boswellic acid and its structural related derivatives, has been used as a traditional medicine for the treatment of inflammatory and arthritic diseases. Topical application of BE to the backs of mice markedly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mice. Feeding 0.2% of BE in the diet to CF-1 mice for 10-24 weeks reduced the accumulation of parametrial fat pad weight under the abdomen, and inhibited azoxymethane (AOM)-induced formation of aberrant crypt foci (ACF) by 46%. Addition of pure beta-boswellic acid, 3-O-acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid or 3-O-acetyl-11-keto-beta-boswellic acid to human leukemia HL-60 cell culture inhibited DNA synthesis in HL-60 cells in a dose-dependent manner with IC50 values ranging from 0.6 to 7.1 microM. These results indicate that beta-boswellic acid and its derivatives (the major constituents of Boswellin) have anti-carcinogenic, anti-tumor, and anti-hyperlipidemic activities.
The inhibitory effects of five tea polyphenols, namely theaflavin (TF1), theaflavin-3-gallate (TF2), theaflavin-3,3'-digallate (TF3), (-)-epigallocatechin-3-gallate (EGCG), and gallic acid, and propyl gallate (PG) on xanthine oxidase (XO) were investigated. These six antioxidant compounds reduce oxidative stress. Theaflavins and EGCG inhibit XO to produce uric acid and also act as scanvengers of superoxide. TF3 acts as a competitive inhibitor and is the most potent inhibitor of XO among these compounds. Tea polyphenols and PG all have potent inhibitory effects (>50%) on PMA-stimulated superoxide production at 20 approximately 50 microM in HL-60 cells. Gallic acid (GA) showed no inhibition under the same conditions. At 10 microM, only EGCG, TF3, and PG showed significant inhibition with potency of PG > EGCG > TF3. The superoxide scavenging abilities of these six compunds are as follows: EGCG > TF2 > TF1 > GA > TF3 > PG. PG was the most potent inhibitor of PMA-stimulated H(2)O(2) production in HL-60 cells. The order of H(2)O(2) scavenging ability was TF2 > TF3 > TF1 > EGCG > PG > GA. Therefore, the antioxidative activity of tea polyphenols and PG is due not only to their ability to scavenge superoxides but also to their ability to block XO and related oxidative signal transducers.
This study examined the growth inhibitory effects of theasinensin A (from oolong tea) and black tea polyphenols, including theaflavin (TF-1), a mixture (TF-2) of theaflavin-3-gallate (TF-2a) and theaflavin-3'-gallate (TF-2b), and theaflavin-3,3'-digallate (TF-3) in human cancer cells. Theasinensin A, TF-1, and TF-2 displayed strong growth inhibitory effects against human histolytic lymphoma U937, with estimated IC50 values of 12 microM, but were less effective against human acute T cell leukemia Jurkat, whereas TF-3 and (-)-epigallocatechin-3-gallate (EGCG) had lower activities. The molecular mechanisms of tea polyphenol-induced apoptosis as determined by annexin V apoptosis assay, DNA fragmentation, and caspase activation were further investigated. Loss of membrane potential and reactive oxygen species (ROS) generation were also detected by flow cytometry. Treatment with tea polyphenols caused rapid induction of caspase-3, but not caspase-1, activity and stimulated proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Pretreatment with a potent caspase-3 inhibitor, Z-Asp-Glu-Val-Asp-fluoromethyl ketone, inhibited theasinensin A induced DNA fragmentation. Furthermore, it was found that theasinensin A induced loss of mitochondrial transmembrane potential, elevation of ROS production, release of mitochondrial cytochrome c into the cytosol, and subsequent induction of caspase-9 activity. These results indicate that theasinensin A allows caspase-activated deoxyribonuclease to enter the nucleus and degrade chromosomal DNA and induces DFF-45 (DNA fragmentation factor) degradation. The results suggest that induction of apoptosis by theasinensin A may provide a pivotal mechanism for their cancer chemopreventive function.
Six compounds, 1-O-(2,3, 4-trihydroxy-3-methyl)butyl-6-O-feruloyl-beta-D-glucopyranoside, ethyl beta-D-glucopyranosyl tuberonate, p-hydroxybenzoic acid, (-)-hydroxyjasmonic acid, caffeic acid, and 4-hydroxyacetophenone 4-O-[5-O-(3, 5-dimethoxy-4-hydroxybenzoyl)-beta-D-apiofrunosyl]-(1-->2)-beta-D- glu copyranoside, were isolated from the n-butanol-soluble fraction of sage leaf extracts. Their structures were determined by spectral methods (MS, NMR, and 2D-NMR), and their antioxidant activities were measured. Among them, two new glycosides were elucidated. All of these compounds showed DPPH free radical scavenging activity at the concentration of 30 mM, and caffeic acid was the most active compound.
The roots of two varieties of Polygonum cuspidatum (Hu Zhang and Mexican Bamboo) were analyzed for resveratrol and analogues. The roots of each variety were dried and ground into a powder. The powdered roots were then extracted with methanol and ethyl acetate. The ethyl acetate fraction of the Mexican Bamboo was then subjected to fractionation and purification using silica gel column chromatography and semipreparative HPLC. In addition to resveratrol (3,5,4'-trihydroxystilbene), three stilbene glucosides were identified by (1)H NMR, (13)C NMR, and MS. The stilbene glucosides were shown to be a piceatannol glucoside (3,5,3', 4'-tetrahydroxystilbene 4'-O-beta-D-glucopyranoside), resveratroloside (3,5,4'-trihydroxystilbene 4'-O-beta-D-glucopyranoside), and piceid (3,5,4'-trihydroxystilbene 3-O-beta-D-glucopyranoside). The levels of the piceatannol glucoside and piceid were twice as high in the Mexican Bamboo as compared to the Hu Zhang.
Urea occurs naturally in many food products, and its presence affects food quality. However, little is known about its impact on flavor generation in food production. In this study, the urea contents in beef, pork, and chicken were determined. The effects of urea and pH on thermal flavor generation were investigated using the model system of cysteine with ribose, which was heated to the roasting temperature of 180 degrees C for 2 h at pH 5 and pH 8.5. The results revealed relatively large amounts of urea in these meats and demonstrated that pH affects aroma generation. Volatiles identified from the reaction system of ribose and cysteine showed that sulfur-containing compounds such as thiophenes, thiazoles, and thiophenethiols were the most abundant compounds. The addition of urea into the reaction mixture caused the disappearance or reduction in content of some sulfur-containing compounds but resulted in the generation of several important nitrogen-containing volatiles, like pyrazine, methylpyrazine, 2,5- (and 2,6-)dimethylpyrazine and other alkylpyrazines, which are known to elicit roasty, nutty flavor notes. A plausible explanation for this phenomenon is that ammonia can be released from urea upon heating and the formed ammonia competes with hydrogen sulfide to react with Maillard reaction precursors to produce nitrogen-containing compounds such as alkylpyrazines.
(-)-Epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) are two important antioxidants in tea. They also display some antitumor activities, and these activities are believed to be mainly due to their antioxidative effects. However, the specific mechanisms of antioxidant action of tea catechins remain unclear. In this study are isolated and identified two novel reaction products of EGCG and one product of EGC when they were reacted separately with H(2)O(2). These products are formed by the oxidation and decarboxylation of the A ring in the catechin molecule. This study provides unequivocal proof that the A ring of EGCG and EGC may also be an antioxidant site. This study also indicates an additional reaction pathway for the oxidation chemistry of tea catechins.