Biomedical subjects

C F Chen

Publications and source records attributed to C F Chen.

At least 37 records · Page 2Linked to original sources

PubMed2001

Induction of cytochrome P450-dependent monooxygenase in mouse liver and kidney by rutaecarpine, an alkaloid of the herbal drug Evodia rutaecarpa.

Rutaecarpine is one of the main alkaloids of an herbal remedy, Evodia rutaecarpa, which has been used for the treatment of gastrointestinal disorder and headache. Effects of rutaecarpine on hepatic and renal cytochrome P450 (CYP)-dependent monooxygenase were studied in C57BL/6J mice. Treatment of mice with rutaecarpine by gastrogavage at 50 mg/kg/day for three days resulted in 57%, 41%, 6-, and 6-fold increases of hepatic microsomal benzo(a)pyrene hydroxylation, 7-ethoxycoumarin O-deethylation, 7-ethoxyresorufin O-deethylation, and 7-methoxyresorufin O-demethylation activities, respectively. However, the treatment had no effects on hepatic oxidation activities toward benzphetamine, N-nitrosodimethylamine, nifedipine, and erythromycin. In the kidney, rutaecarpine-treatment resulted in 2-fold and 42% increases of microsomal benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation activities, respectively. The treatment also increased renal 7-ethoxyresorufin O-deethylation activity to a detectable level. Immunoblot analysis of microsomal proteins showed that rutaecarpine-treatment increased the protein levels of CYP1A1 and CYP1A2 in the liver, whereas hepatic level of CYP3A-immunoreacted protein was not affected by rutaecarpine. These CYPs were not detectable in the immunoblot analyses of control and rutaecarpine-treated mouse kidney microsomes. These results indicated that rutaecarpine was a CYP1A inducer and showed potent inductive effects on both CYP1A1 and CYP1A2 in the liver.

Administration, Oral↗

PubMed2001

Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells in male rats.

Evodiamine is a bioactive alkaloid extracted from a Chinese herb named Wu-Chu-Yu, which possesses thermoregulatory, analgesic, and cardiovascular effects. Some studies have demonstrated that evodiamine reduces blood pressure through acting on endothelium and smooth muscle cells to produce a vasodilatory effect, but whether it affects aldosterone secretion is unclear. The purpose of this study was to examine the effect of evodiamine on aldosterone release in adrenal zona glomerulosa (ZG) cells. ZG cells were isolated from the adrenal glands of adult male rats and incubated with angiotensin II (Ang II, 1x10(-7) M) and 3H-pregnenolone in the presence or absence of evodiamine (1x10(-6)-1x10(-3) M) at 37 degrees C for one hour. The concentration of aldosterone in the media was measured by a radioimmunoassay. The level of radioactivity incorporated into aldosterone and its precursors after incubation of ZG cells with 3H-pregnenolone was analyzed by thin-layer chromatography. The results demonstrated that evodiamine decreased the basal level of and Ang II-induced release level of aldosterone in rat ZG cells. Administration of evodiamine also decreased the level of radioactivity incorporated into 3H-corticosterone and 3H-aldosterone following incubation of ZG cells with 3H-pregnenolone. This suggest that evodiamine affects aldosterone release in rat adrenal glomerulosa cells by acting on Ang II-associated pathway and reducing the activity of 11 beta-hydroxylase (an enzyme which coverts deoxycorticosterone to corticosterone) during the steroidogenesis of aldosterone.

Aldosterone↗

PubMed2001

Camptothecin suppresses nitric oxide biosynthesis in RAW 264.7 macrophages.

Nitric oxide is an important cellular mediator that plays a role in tumor growth and angiogenesis. The present study was conducted to evaluate whether camptothecin (CPT), a topoisomerase I inhibitor, exhibits antitumor activity through regulation the inducible nitric oxide synthase (iNOS) biosynthesis pathway. Experiment was performed on RAW 264.7 cells, a transformed macrophage-like cell line, stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). Incubation of RAW264.7 cells with CPT (0.1 to 10 microM) inhibited the LPS/IFN-gamma-induced nitrite accumulation in a concentration-dependent manner with an IC50 value of 0.59+/-0.07 microM. Treatment of cells with concentrations of CPT (< or =3 microM) that are not growth inhibitory or cytotoxic strongly inhibited their ability to express iNOS mRNA and iNOS protein, however, without a direct regulatory effect on iNOS activity. Time course analysis also revealed that CPT acted in a fashion similar to the transcription inhibitor actinomycin-D. Thus, the suppressant effects of CPT on LPS/IFN-gamma-stimulated NO production seemed to be mediated probably through inhibition of iNOS gene transcription. From this observation we propose that inhibition of NO biosynthesis by CPT may underlie, at least in part, the efficacy of this antitumor agent.

Animals↗

PubMed2001

Patterns of retinal ganglion cell survival after brain-derived neurotrophic factor administration in hypertensive eyes of rats.

We investigated the effect of brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival after intraocular pressure (IOP) elevation at various time intervals. In adult Wistar rats, RGCs were labeled with 5% Fluorogold. Animals with 1.8-2.5-fold increase in IOP after cauterization of three episcleral vessels, were divided into three BDNF groups and three vehicle control groups, each receiving one, two or three injections. The RGC survival percentage on RGCs of the first, second and third injections were 93.9% (n = 7), 91.3% (n = 7), 82.7% (n = 5), respectively in BDNF groups; 91.6% (n = 6), 84.1% (n = 6) and 73.5% (n = 5), respectively in vehicle controls. The second and third injections of BDNF showed statistically significant survival effects. These findings demonstrated that BDNF has partial neuroprotection on RGCs in whole retina and enhances RGC survival in moderately chronic hypertensive eyes.

Animals↗

PubMed2001

Effect of cyclosporine, a P-glycoprotein inhibitor, on the pharmacokinetics of cefepime in rat blood and brain: a microdialysis study.

In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p<0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p<0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Cardiac effects of the extract and active components of radix stephaniae tetrandrae. II. Myocardial infarct, arrhythmias, coronary arterial flow and heart rate in the isolated perfused rat heart.

The primary purpose of the present study was to compare the cardioprotective effects of the extract from radix stephaniae tetrandrae (RST) and its individual compounds, tetrandrine (Tet) and fanchinoline (Fan). Secondly, we also compared the cardiac effects of the individual compounds and the RST extract with those of verapamil, a classical Ca2+ channel blocker. The Langendorff isolated perfused rat heart preparation was used. Regional ischaemia and reperfusion was employed to induce myocardial infarct and arrhythmia. Infarct, arrhythmia, heart rate and coronary artery flow were determined in hearts treated with vehicle, RST extract, Tet, Fan, or verapamil. It was found that RST extract, of which only 9% was Tet, and Tet alone produced equally potent ameliorating effects on arrhythmia and infarct induced by ischaemia and reperfusion without further inhibiting ischaemia-reduced heart rate and coronary artery flow. Fan had no effects on arrhythmia and infarct induced by ischaemia and reperfusion; but it induced S-T segment elevation and further reduced heart rate and coronary artery flow during ischaemia. Verapamil also ameliorated the effects of ischaemia and reperfusion on arrhythmia and infarct. It should be noted that 1 microM verapamil, that produced comparable effects on infarct and arrhythmia to the RST extract and Tet, further inhibited heart rate during ischaemia. The results indicate that the RST extract produces equally potent cardioprotective and anti-arrhythmic effects as Tet alone. Both RST extract and Tet may be better choices for the treatment of arrhythmia and infarct induced by myocardial ischaemia and reperfusion than the classical Ca2+ channel blocker, verapamil as they do not further reduce heart rate during ischaemia.

Alkaloids↗

PubMed2001

Cardiac effects of the extract and active components of Radix stephaniae tetrandrae. I. Electrically-induced intracellular calcium transient and protein release during the calcium paradox.

The present study was designed to compare the cardiac actions of the extract and individual components, tetrandrine (Tet) and fangchinoline (Fan), of Radix stephaniae tetrandrae (RST). We measured the electrically induced [Ca2+]i transient in single rat ventricular myocytes and protein release following perfusion with a Ca2+ free solution (the Ca2+ paradox) from the isolated perfused rat heart, both of which are known to relate to Ca2+ influx. We found that Tet inhibited both electrically induced [Ca2+]i transient and protein release during the Ca2+ paradox, while Fan had no significant effects. The RST extract containing 9% Tet and 6% Fan by weight also affected the [Ca2+]i transient, and was only slightly, though significantly, less effective/potent than Tet alone. On the other hand, RST extract had a significantly greater inhibitory effect on protein release during the Ca2+ paradox than Tet alone. The observations suggest that the RST extract, which contains a mixture of components, may have more potent effects in the heart than its main active component.

Alkaloids↗

PubMed2001

On-line microdialysis coupled with microbore liquid chromatography with ultraviolet detection for continuous monitoring of free cefsulodin in rat blood.

A microdialysis method followed by a microbore liquid chromatographic ultraviolet detection procedure has been performed for the assay of unbound cefsulodin in rat blood. A microdialysis probe was inserted into the jugular vein for blood sampling. This method involves an on-line design for submitting dialysate into the liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (10:90, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 265 nm. Microdialysis probes, being laboratory-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of cefsulodin in the blood following intravenous administration of cefsulodin (20 mg/kg) in rats. Pharmacokinetics were calculated from the corrected data for dialysate concentrations of cefsulodin versus time. Based on pharmacokinetic calculation, cefsulodin best fitted to a two-exponential disposition. This study provided specific pharmacokinetic information for protein-unbound cefsulodin and demonstrated the applicability of this continuous sampling method for pharmacokinetic study.

Animals↗

PubMed2001

Determination and pharmacokinetic study of unbound cefepime in rat bile by liquid chromatography with on-line microdialysis.

Biliary excretion and intestinal reabsorption in enterohepatic circulation play major dispositional roles for some drugs. To investigate biliary excretion of drug, we inserted a microdialysis probe into the bile common duct of rat between the liver and the duodenum. In order to avoid the obstruction of bile fluid or bile salt waste, a shunt linear microdialysis probe was used for simultaneous and continuous sampling following intravenous administration of cefepime (50 mg/kg, i.v.). Separation and quantitation of cefepime in the dialysates were achieved using a LiChrosorb RP-18 column (Merck; 250x4.6 mm I.D., particle size 5 microm) maintained at ambient temperature. Samples were eluted with a mobile phase containing 100 mM monosodium phosphoric acid (pH 3.0)-methanol (87:13, v/v). The UV detector wavelength was set at 270 nm. The result indicates that the elimination half-life of cefepime in bile was 64.01+/-9.32 min. This study also served as an example for the microdialysis application in the biliary excretion study of drug.

Animals↗

PubMed2001

Dehydroevodiamine attenuates beta-amyloid peptide-induced amnesia in mice.

Dehydroevodiamine has been reported to have anticholinesterase activity and an anti-amnesic effect. This study examined the effects of dehydroevodiamine on scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia in mice, using a step-through passive avoidance test. Similarly to the cholinesterase inhibitor, physostigmine (0.03--0.3 mg/kg, i.p.), dehydroevodiamine (0.75--12.0 mg/kg, i.p.) administered 30 min before the training trial, immediately after the training trial, and 30 min before the retention test significantly improved scopolamine- and beta-amyloid peptide-(25--35)-induced amnesia. In beta-amyloid peptide-(25--35)-induced amnesia, the rank order of anti-amnesic potency in these three administration schedules for dehydroevodiamine was different from that for physostigmine. Furthermore, dehydroevodiamine was more potent to improve beta-amyloid peptide-(25--35)-induced amnesia than scopolamine-induced amnesia when administered before the training trial. These results suggested that dehydroevodiamine may have an action other than that of an anticholinesterase and may be a novel and effective ligand for improvement of beta-amyloid type amnesia.

Alkaloids↗

PubMed2001

Measurement and pharmacokinetic analysis of unbound ceftazidime in rat blood using microdialysis and microbore liquid chromatography.

To evaluate the biodisposition of ceftazidime in rat blood, a rapid and simple microbore liquid chromatographic technique together with a microdialysis sampling technique were developed. This method involves an on-line design for blood dialysate directly injected into a microbore liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-acetonitrile-100 mM monosodium phosphoric acid (pH 3.0) (10:10:80, v/v/v) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. With the detection wavelength set at 254 nm, a good linear correlation was observed between the peak area and the ceftazidime concentration at 0.1 to 50 microg/ml (r=0.999). Microdialysis probes, being custom-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity, as well as intra-day and inter-day variabilities. This method was then applied to the pharmacokinetic profiling of ceftazidime in blood following intravenous 50 mg/kg administration to rats. The pharmacokinetics was calculated from the corrected data for dialysate concentrations of ceftazidime versus time. This method has been used to study ceftazidime pharmacokinetics in rats and has proven to be rapid and reproducible.

Animals↗

PubMed2001

Renal response during acute unilateral ureteral obstruction in rats.

The early renal response to unilateral ureteral occlusion (UUO) and its mechanism have been extensively studied in dogs but seldom discussed in the most frequently used laboratory animals, rats. The acute phase of the renal response to UUO was studied in female rats weighing 190-236 g. We recorded the ureteral pressure and changes in renal parameters throughout 120 minutes of UUO in control (US, UUO + saline, n = 10), L-arginine-treated (UA, n = 10), and right-nephrectomized rats (UO, UUO in one kidney, n = 9). Ureteral pressure increased in all three groups of rats after complete ureteral obstruction. The extent of the increase was not significantly different between US and UA rats but was significantly higher in the UO rats. In US rats, the cortical microvascular blood flow (CMVBF), measured by a laser Doppler flowmeter, declined significantly, from 321 +/- 10 perfusion units (PU) to 260 +/- 11 PU. The percentage of drop in CMVBF at 120 minutes of UUO was significantly greater in UO (25.7 +/- 3.8 %) than in US (19 +/- 2.1%) and in UA (14 +/- 2%) rats. Acute UUO reduced the glomerular filtration rate (GFR) in US and UO rats, whereas L-arginine attenuated this decrease. The excretion of nitrate/nitrite was increased after UUO. Giving N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 12 mg/kg/h) during UUO did not reduce CMVBF more severely. Western blot analysis of endothelial nitric oxide synthase expression in the renal cortex and medulla protein extracts revealed no differences between US and sham-operated rats. Acute UUO did not lead to renal hyperemia in rats. Reduction of nitric oxide during UUO might contribute to the decrease of renal circulation during UUO.

Acute Disease↗

PubMed2001

Measurement and pharmacokinetic analysis of unbound cephaloridine in rat blood by on-line microdialysis and microbore liquid chromatography.

A technique involving rapid sampling of cephaloridine in rat blood was achieved using a combination of microdialysis and sensitive microbore liquid chromatography. A microdialysis probe was inserted into the jugular vein/right atrium of a Sprague-Dawley rat. Then after a real-time collection of the analyte by microdialysis, the dialysate was automatically injected into a liquid chromatographic system via an on-line injector. Following a 2 h stabilization period after the surgical procedure, cephaloridine (20 mg/kg, i.v.) was then administered via the femoral vein. Isocratic elution of cephaloridine was carried out with a mobile phase containing methanol-20 mM monosodium phosphate (25:75, v/v, pH 5.5), and the flow rate of the mobile phase was 0.05 mL/min within 10 min. Intra- and inter-assay accuracy and precision of the assay were each less than 10%. The in vivo recovery of the cephaloridine from the microdialysate was 49.7 +/- 8.0% and 42.4 +/- 8.4% for 0.5 and 1 microg/mL standards (n = 6), respectively. Based on the pharmacokinetic analysis, the elimination half-life was 32.2 +/- 8.6 min by cephaloridine administration (20 mg/kg, i.v., n = 6).

Animals↗

PubMed2001

Spasmolytic effects of three harmala alkaloids on guinea-pig isolated trachea.

The present study examined and compared the spasmolytic effects of 3 harmala alkaloids, harmine, harman, and harmaline, on carbachol-, histamine-, and KCl-induced contractions of guinea-pig isolated tracheal preparations. All 3 compounds relaxed the tracheal preparations contracted by these spasmogens with similar or different EC50 values, harmine being the most potent one. The cumulative concentration-response curves of all 3 compounds for carbachol-induced contraction were shifted to the right by propranolol (1 microM) pretreatment, indicating the involvement of the activation on the beta-adrenoceptors. All 3 compounds shifted the concentration-response curves of carbachol to the right in a parallel manner with the pA2 values comparable with their relaxation EC50 values, indicating a competitive antagonism at the muscarinic receptors. Receptor binding assays indicated that all 3 compounds interacted with lung muscarinic receptors (Ki = 11-13 microM), histamine H1 receptors (Ki = 27-107 microM), and beta2-adrenoceptors (Ki = 20-51 microM). Therefore, in addition to their actions on receptor-linked and voltage-dependent Ca2+ channels as reported in other types of smooth muscle, the present study suggests that the actions on muscarinic receptors, histamine H1 receptors, and beta2-adrenoceptors are also involved in their spasmolytic effects on airway smooth muscles.

Adrenergic beta-Antagonists↗

PubMed2001

Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea.

We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca(2+)-induced contractions in depolarized (K+, 60 mM; histamine, 100 microM; or carbachol, 10 microM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 microM)-remaining tension of carbachol (0.2 microM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), N omega-nitro-L-arginine (20 microM), or alpha-chymotrypsin (1 U/ml). However, S-petasin (100-300 microM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.

Animals↗

PubMed2001

Vasorelaxing effect of coumarins from Cnidium monnieri on rabbit corpus cavernosum.

Bioassay-directed fractionation led to the identification of four known coumarins, osthole (1), imperatorin (2), xanthotoxin (3), and isopimpinellin (4), from the ethanolic extract of the fruit of Cnidium monnieri (L.) Cusson. In phenylephrine (PE)-precontracted endothelium-intact rabbit corpus cavernosum, all four coumarins exhibited relaxing effect with the IC50 values for compounds 1, 2, 3, and 4 determined to be 2.14 +/- 0.73, 0.85 +/- 0.16, 1.24 +/- 0.45, and 18.4 +/- 8.10 microM, respectively. The four compounds were identified by comparison of their physical data (EIMS, 1H- and 13C-NMR) with those from published reports.

Animals↗

PubMed2001

Effect of ginseng saponins on beta-amyloid-suppressed acetylcholine release from rat hippocampal slices.

In view of the facts that ginseng has been shown to improve age-related memory deficits and beta-amyloid-related peptides have been suggested to play a significant role in memory degeneration in the elderly, the present study was carried out to examine the effect of various ginsenosides on beta-amyloid peptides-modulated acetylcholine (ACh) release, a key neurotransmitter in memory processing, from the hippocampal slices. Addition of beta-amyloid fragment(25 - 35) (0.01 - 1 microM) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner and about 40 % reduction in ACh outflow was observed when incubating with the highest concentration of an amyloid fragment (1 microM). Inclusion of the ginsenoside components Rb(1) (0.1 microM), but not Rg(1), caused a rightward shift of the concentration-response curve of beta-amyloid. The reversal of the beta-amyloid-inhibited ACh release by Rb(1) was not blocked by tetrodotoxin (1 microM) indicating that an interaction occurs at the cholinergic synapse. These results suggest that Rb(1) may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides.

Acetylcholine↗

PubMed2001

Isolation and characterization of an active compound from black soybean [Glycine max (L.) Merr.] and its effect on proliferation and differentiation of human leukemic U937 cells.

Black soybean [Glycine max (L.) Merr.] has been used as a health food and herb in China for hundreds of years. In the present study, we purified a unique polysaccharide component from black soybean (PSBS) and found that it indirectly inhibits proliferation and induces differentiation of human leukemic U937 cells via activation of mononuclear cells (MNCs). We prepared conditioned media (MNC-CM) by incubating MNCs from human peripheral blood with or without PSBS (PSBS-MNC-CM and normal MNC-CM, respectively). Treatment of human leukemic U937 cells with PSBS-MNC-CM significantly inhibited proliferation of U937 cells, reducing their growth by 98.5%. Furthermore, PSBS-MNC-CM induced U937 cells to differentiate into mature monocytes/macrophages (83% by morphological examination and 90% by the nitroblue tetrazolium test). Neither PSBS alone nor normal MNC-CM had such effects. The molecular weight of PSBS was about 480 000 by gel filtration. Structural analysis of PSBS revealed that (1,6)-alpha-D-glucan might be its major active component. Our results suggest that the PSBS may inhibit proliferation and induce differentiation in human leukemic U937 cells by activating the immune response of MNCs.

Adult↗