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Biomedical subjects

L L Yang

Publications and source records attributed to L L Yang.

At least 19 recordsLinked to original sources
PubMed2001

Camelliin B induced apoptosis in HeLa cell line.

Gordonia axillaris (Roxb.) Dietrich (Theaceae) is a native to Taiwan and the leaves have been used as an astringent folk medicine. Camelliin B (CB), a macrocyclic hydrolyzable tannin, was isolated from G. axillaris and showed cytotoxic effects in human carcinoma cells. Among the target cells (SKHep-1, Ha-22T, DU-145, AGS, and HeLa), the cervical carcinoma cell line, HeLa, was more sensitive to CB than were Chang normal liver cells and primary-cultured normal gingival and cervical fibroblasts. Furthermore, the cytotoxic effects of CB showed dose-dependency at 3.2-100.0 microg/ml in HeLa for 1,24,48, and 72 h and with an IC(50) value of 46.3 microg/ml for 48 h. However, the IC(50) value of CB in primary-cultured normal cervical fibroblasts was 108.0 microg/ml. Therefore, the selectivity shown by CB was ascribed to the difference in growth speed between normal and tumor cells. HeLa cells and primary-cultured normal cervical fibroblasts were treated with 50.0 and 100.0 microg/ml CB for 48 h, respectively, and exhibited chromatin condensation, indicating the occurrence of apoptosis. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at the G(1) phase, and a concomitant increase of cell population at the G(2)/M phase. CB also caused DNA fragmentation and inhibited PARP degradation in HeLa cells. However, CB did not significantly inhibit Bcl-2 expression in HeLa cells at 50.0 microg/ml, only at 100.0 microg/ml for 48 h. These results suggest that CB induced apoptosis, without direct inhibition of Bcl-2 expression in HeLa cells.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Wogonin, baicalin, and baicalein inhibition of inducible nitric oxide synthase and cyclooxygenase-2 gene expressions induced by nitric oxide synthase inhibitors and lipopolysaccharide.

We previously reported that oroxylin A, a polyphenolic compound, was a potent inhibitor of lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In the present study, three oroxylin A structurally related polyphenols isolated from the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, were examined for their effects on LPS-induced nitric oxide (NO) production and iNOS and COX-2 gene expressions in RAW 264.7 macrophages. The results indicated that these three polyphenolic compounds inhibited LPS-induced NO production in a concentration-dependent manner without a notable cytotoxic effect on these cells. The decrease in NO production was in parallel with the inhibition by these polyphenolic compounds of LPS-induced iNOS gene expression. However, these three compounds did not directly affect iNOS enzyme activity. In addition, wogonin, but not baicalin or baicalein, inhibited LPS-induced prostaglandin E2 (PGE2) production and COX-2 gene expression without affecting COX-2 enzyme activity. Furthermore, N-nitro-L-arginine (NLA) and N-nitro-L-arginine methyl ester (L-NAME) pretreatment enhanced LPS-induced iNOS (but not COX-2) protein expression, which was inhibited by these three polyphenolic compounds. Wogonin, but not baicalin or baicalein, similarly inhibited PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS-co-treated RAW 264.7 cells. These results indicated that co-treatment with NOS inhibitors and polyphenolic compounds such as wogonin effectively blocks acute production of NO and, at the same time, inhibits expression of iNOS and COX-2 genes.

Animals↗
PubMed2001

Activity staining of isocitrate lyase after electrophoresis on either native or sodium dodecyl sulfate polyacrylamide gels.

Isocitrate was cleaved into succinate and glyoxylate by isocitrate lyase (ICL) in the glyoxylate cycle. We used lactate dehydrogenase as an ancillary enzyme to further metabolize the glyoxylate to glycolate in the presence of NADH. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and 2,6-dichlorophenol-indolphenol (DCPIP) were used in the coupling reactions for detecting ICL activity after electrophoresis on either native or sodium dodecyl sulfate (SDS) polyacrylamide gels. This fast and sensitive method can be used in the process of ICL enzyme purification and characterization.

Acrylic Resins↗
PubMed2001

Inhibition of nitric oxide synthase inhibitors and lipopolysaccharide induced inducible NOS and cyclooxygenase-2 gene expressions by rutin, quercetin, and quercetin pentaacetate in RAW 264.7 macrophages.

Several natural flavonoids have been demonstrated to perform some beneficial biological activities, however, higher-effective concentrations and poor-absorptive efficacy in body of flavonoids blocked their practical applications. In the present study, we provided evidences to demonstrate that flavonoids rutin, quercetin, and its acetylated product quercetin pentaacetate were able to be used with nitric oxide synthase (NOS) inhibitors (N-nitro-L-arginine (NLA) or N-nitro-L-arginine methyl ester (L-NAME)) in treatment of lipopolysaccharide (LPS) induced nitric oxide (NO) and prostaglandin E2 (PGE2) productions, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) gene expressions in a mouse macrophage cell line (RAW 264.7). The results showed that rutin, quercetin, and quercetin pentaacetate-inhibited LPS-induced NO production in a concentration-dependent manner without obvious cytotoxic effect on cells by MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide as an indicator. Decrease of NO production by flavonoids was consistent with the inhibition on LPS-induced iNOS gene expression by western blotting. However, these compounds were unable to block iNOS enzyme activity by direct and indirect measurement on iNOS enzyme activity. Quercetin pentaacetate showed the obvious inhibition on LPS-induced PGE2 production and COX-2 gene expression and the inhibition was not result of suppression on COX-2 enzyme activity. Previous study demonstrated that decrease of NO production by L-arginine analogs effectively stimulated LPS-induced iNOS gene expression, and proposed that stimulatory effects on iNOS protein by NOS inhibitors might be harmful in treating sepsis. In this study, NLA or L-NAME treatment stimulated significantly on LPS-induced iNOS (but not COX-2) protein in RAW 264.7 cells which was inhibited by these three compounds. Quercetin pentaacetate, but not quercetin and rutin, showed the strong inhibitory activity on PGE2 production and COX-2 protein expression in NLA/LPS or L-NAME/LPS co-treated RAW 264.7 cells. These results indicated that combinatorial treatment of L-arginine analogs and flavonoid derivates, such as quercetin pentaacetate, effectively inhibited LPS-induced NO and PGE2 productions, at the same time, inhibited enhanced expressions of iNOS and COX-2 genes.

Animals↗
PubMed2001

Peters' anomaly. A synopsis of surgical management and visual outcome.

Peters' anomaly is not an isolated anterior segment abnormality, but occurs as a diverse, phenotypically heterogeneous condition associated with multiple underlying ocular and systemic defects. Surgical treatment of Peters' anomaly is a complex and challenging undertaking. The broad spectrum of disease severity, the lack of uniformity in clinical features, the differences and overlap of preoperative risk factors, and the variability in the numbers and types of intraocular procedures that are performed on individual eyes, as well as postoperative complications all contribute to the difficulties involved in surgical management. This article discloses useful information pertaining to keratoplasty for Peters' anomaly. The study by Yang et al showed that long-term graft clarity could be achieved in 36% of eyes. However, 93% of all clear grafts were first grafts, whereas only 7% were second grafts. All third or subsequent grafts failed. Other important findings were: (1) the significantly greater chance of maintaining a clear graft with initial grafts, compared with subsequent grafts; (2) the disclosure of periods of differential risk for graft failure; and (3) the identification of risk factors for graft failure. Surgical intervention involving one or more procedures is effective in controlling IOP in 32% of eyes with associated congenital glaucoma. Still, multiple procedures and adjunctive medical therapy are often required to achieve and maintain adequate IOP control. The visual outcome is guarded in children with Peters' anomaly. Achieving a satisfactory visual outcome and preventing further visual loss is impeded by the presence of congenital anterior and posterior segment anomalies, structural defects of the CNS, cognitive dysfunction and amblyopia, as well as postoperative complications such as graft failure, cataract, inoperable retinal detachment, and phthisis.

Anterior Eye Segment↗
PubMed2001

Antioxidant activities of trypsin inhibitor, a 33 KDa root storage protein of sweet potato (Ipomoea batatas (L.) Lam cv. Tainong 57).

Trypsin inhibitors (TIs), root storage proteins, were purified from sweet potato (Ipomoea batatas[L.] Lam cv. Tainong 57) roots by trypsin affinity column according to the methods of Hou and Lin (Plant Sci. 1997, 126, 11-19 and Plant Sci. 1997, 128, 151-158). A single band of 33 kDa TI was obtained by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. This purified 33 kDa TI had scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. There was positive correlation between scavenging effects against DPPH (2 to 22%) and amounts of 33 kDa TI (1.92 to 46 pmol). The scavenging activities of 33 kDa TI against DPPH were calculated from linear regression to be about one-third of those of glutathione between 5 and 80 pmol. Using electron paramagnetic resonance (EPR) spectrometry for hydroxyl radical detection, it was found that 33 kDa TI could capture hydroxyl radical, and the intensities of EPR signal were significantly decreased from 1.5 to 6 pmol of 33 kDa TI compared to those of the controls. It is suggested that 33 kDa TI, one of the sweet potato root storage proteins, may play a role as an antioxidant in roots and may be beneficial to health when it is consumed.

Antioxidants↗
PubMed2001

Monoamine oxidase B and free radical scavenging activities of natural flavonoids in Melastoma candidum D. Don.

Monoamine oxidase type B (MAO-B) activity and free radicals are elevated in certain neurological diseases. Four natural flavonoids, quercitrin, isoquercitrin, rutin, and quercetin, were isolated for the first time from the leaves of Melastoma candidum D. Don. They exhibited an inhibitory effect on MAO-B. These potent flavonoids were purified using bioassay-guided fractionation and were separated by Diaion, Sephadex LH-20, and MCI CHP20P columns. The IC(50) values of the four potent flavonoids, quercitrin, isoquercitrin, rutin, and quercetin on monoamine oxidase were 19.06, 11.64, 3.89, and 10.89 microM and enzyme kinetics analysis revealed apparent inhibition constants (K(i)) of 21.01, 2.72, 1.83, and 7.95 microM, respectively, on the substrate, benzylamine. The four potent compounds also exhibited hydroxyl radical scavenging activity as determined using a spin trapping electron spin resonance method. This suggests that the four flavonoids from M. candidum possess both MAO-B inhibitory and free radical scavenging activities. These important properties may be used for preventing some neurodegenerative diseases in the future.

Chromatography, High Pressure Liquid↗
PubMed2001

Effects of Paeoniae Radix, a traditional Chinese medicine, on the pharmacokinetics of phenytoin.

BACKGROUND: Phenytoin (PHT), one of the most widely prescribed antiepileptic drugs, has been reported to be associated with numerous drug-drug interactions. However, there are far fewer reports about the pharmacokinetic interactions between PHT and traditional Chinese medicines (TCMs). Paeoniae Radix (PR), one of the well-known TCMs, is used as an adjunct in some epileptic patients. OBJECTIVE: In the present work, we studied the influences of PR on the pharmacokinetics of PHT in rats to identify the possible interactions between PR and PHT. METHOD: A single dose of PHT (100 mg/kg) alone or in combination with PR extract (300 mg/kg) was administered by gavage to male SD rats. Serial blood samples of PHT were obtained for up to 24 h post-administration and measured by high-performance liquid-chromatography. The free (unbound) plasma concentrations of PHT were determined by fluorescence polarization immunoassay. The plasma concentrations were used to construct pharmacokinetic profiles by plotting drug concentration-time curves. All data were subsequently processed by the computer program WINNONLIN. Statistical comparisons of pharmacokinetic parameters were performed with the unpaired Student t-test. RESULTS: The mean maximum plasma concentration of PHT was attained 2 h after oral administration of PHT alone and 4-6 h after oral administration of PHT in combination with PR. The plasma level of PHT declined with a half-life of 5.38 h after PHT alone and 4.03 h after PHT and PR given together. No statistically significant differences were obtained in most of the pharmacokinetic parameters (Cmax, AUC, t1/2, MRT and CL/F) and protein binding rates of PHT between the two treatments. However, significant differences in Tmax and Vd/F between groups were noted. CONCLUSION: The significant increase in Tmax indicated that simultaneous oral administration of PR delayed the absorption of PHT. The delayed absorption of PHT might lead to its slow onset of clinical effect. There were no significant differences in Cmax, AUC, t1/2, MRT and CL/F of PHT between the two groups, showing that PR could not significantly affect the extent of absorption, metabolism and elimination of PHT. No significant difference in protein binding rate was found, indicating that PR might not significantly alter the protein binding of PHT. While a significant decrease in Vd/F was noted, the mechanism underlying the apparently decreased Vd/F of PHT influenced by PR needs further study.

Administration, Oral↗
PubMed2000

Induction of apoptosis by hydrolyzable tannins from Eugenia jambos L. on human leukemia cells.

Eugenia jambos L. (Myrtaceae) is an antipyretic and anti-inflammatory herb of Asian folk medicine. A 70% acetone extract exerted the strongest cytotoxic effects on human leukemia cells (HL-60) from a preliminary screening of 15 plants. The cytotoxic principles were separated by bio-assay-guided fractionation to HL-60 cells; two hydrolyzable tannins (1-O-galloyl castalagin and casuarinin) were isolated from the 70% acetone extract. All significantly inhibited human promyelocytic leukemia cell line HL-60 and showed less cytotoxicity to human adenocarcinoma cell line SK-HEP-1 and normal cell lines of human lymphocytes and Chang liver cells. Thus, these compounds were exhibited the dose-dependent manner in HL-60 cells and the IC(50) were 10.8 and 12.5 microM, respectively. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at G(2)/M phase, and a concomitant increase of cell population at G(1) phase. The apoptosis induced by these two compounds was also demonstrated by DNA fragmentation assay and microscopic observation. These results suggest that the cytotoxic mechanism of both antitumor principle constituents might be the induction of apoptosis in HL-60 cells.

Adenocarcinoma↗
PubMed2000

EBV DNA polymerase inhibition of tannins from Eugenia uniflora.

Nasopharyngeal carcinoma (NPC) is one of the high population malignant tumors among Chinese in southern China and southeast Asia. Epstein-Barr virus (EBV) is a human B lymphotropic herpes virus which is known to be closely associated with NPC. EBV DNA polymerase is a key enzyme during EBV replication and is measured by its radioactivity. The addition of phorbol 12-myristate 13-acetate to Raji cell cultures led to a large increase in EBV DNA polymerase, which was purified by sequential DEAE-cellulose, phosphocellulose and DNA-cellulose column chromatography. Four tannins were isolated from the active fractions of Eugenia uniflora L., which were tested for the inhibition of EBV DNA polymerase. The results showed the 50% inhibitory concentration (IC(50)) values of gallocatechin, oenothein B, eugeniflorins D(1) and D(2) were 26.5 62.3, 3.0 and 3.5 microM, respectively. Furthermore, when compared with the positive control (phosphonoacetic acid), an inhibitor of EBV replication, the IC(50) value was 16.4 microM. In view of the results, eugeniflorins D(1) and D(2) are the potency principles in the inhibition of EBV DNA polymerase from E. uniflora.

Carcinogens↗
PubMed2000

Cytotoxic effects of cantharidin on the growth of normal and carcinoma cells.

Cantharidin is isolated from Mylabris phalerata Pallas and is a potent inhibitor of hepatocellular carcinoma cells (Hep 3B cells). In the present study, the IC(50) values of cantharidin on Hep 3B cells and normal Chang liver cells were found to be 2.2 and 30.2 microM for 36 h, respectively. Furthermore, cantharidin-treated Hep 3B cells induced cell death within 1 h (IC(50)=52.8 microM), suggesting that cantharidin is an acute cytotoxic agent. We found that although cantharidin could induce cell death, it could not directly inhibit the activity of nucleic acid biosynthesis by the cellular incorporation of 3H-thymidine, 3H-uridine or 3H-leucine. Cantharidin-treated Hep 3B cells showed no evidence of major alterations in the cell cycle distribution within 1 h. However, examination of cells after treatment for 36 h showed that cantharidin regulated the cell cycle at the G(2)/M phase. Moreover, the treated Hep 3B cells had a rounded and shrunken appearance. The microvilli of treated Hep 3B cells were reduced in number and replaced by numerous blebs. Other ultrastructural changes following cantharidin treatment included the presence of lipid droplets, swelling of the mitochondria and accumulation of glycogen particles. The findings of damaged mitochondria in the cantharidin treated Hep 3B cells in this study suggest that cantharidin can induce acute and lethal toxic effects on Hep 3B cells by inhibiting the mitochondria energy system. In conclusion, this study had demonstrated that cantharidin could inhibit progression of all phases of the Hep 3B cell cycle.

Animals↗
PubMed2000

Cuphiin D1, the macrocyclic hydrolyzable tannin induced apoptosis in HL-60 cell line.

Cuphiin D1 (CD1), a new macrocyclic hydrolyzable tannin isolated from Cuphea hyssopifolia, has been shown to exert antitumor activity both in vitro and in vivo. In this study, we explored the mechanism of the CD1-induced antitumor effect on human promyelocytic leukemia (HL-60) cells. The results showed that CD1 induced cytotoxicity in HL-60 cells and the IC50 was 16 microM after 36 h treatment. HL-60 cells treated with CD1 for 36 h decreased the uptake of [3H]-labeled thymidine, uridine and leucine in a dose dependent manner. Electron micrographs demonstrated that HL-60 cells treated with 16 microM CD1 for 36 h exhibited chromatin condensation, indicating the apoptosis occurrence. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at G2/M phase, and a concomitant increase of cell population at G1 phase. CD1 also caused DNA fragmentation and inhibited Bcl-2 expression in the HL-60 cells. These results suggest that the inhibition of Bcl-2 expression in HL-60 cell might account for the mechanism of CD1-induced apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Monitoring of extracellular pyruvate, lactate, and ascorbic acid during cerebral ischemia: a microdialysis study in awake gerbils.

In vivo microdialysis coupled with liquid chromatography was developed for the continuous monitoring of brain neurochemicals during cerebral ischemia in awake, free moving gerbils. The dead volume of the microdialysis system was estimated to be less than 30 microl. The detection limits of the present assay were 0.2 to 2.0 microM for analytes at a signal to noise ratio of five. To validate this assay, a focal cerebral ischemia was produced by occlusion of one common carotid artery for 60 min and then reperfusion for additional 3 h in awake gerbils. A microdialysis probe was inserted into the striatum of the gerbil. Dialysates were autoinjected and analyzed extracellular pyruvate, lactate, and ascorbic acid by liquid chromatography with a UV detector during cerebral ischemia. Significant changes of pyruvate and the lactate/pyruvate ratio were observed. Biphasic and dynamic changes in ascorbic acid and lactate were proposed to correlate a secondary damage. This assay can be used as a tool to study dynamic changes of brain neurochemicals in awake animals.

Animals↗
PubMed2000

Tonic pupil associated with congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome.

PURPOSE: To report the association of tonic pupil, congenital neuroblastoma, Hirschsprung disease, and central hypoventilation syndrome. METHODS: Case reports. RESULTS: Two infants with central hypoventilation syndrome and Hirschsprung disease were evaluated for dilated, nonreactive pupils present since birth. In both cases, pharmacologic testing with dilute pilocarpine confirmed denervation supersensitivity consistent with tonic pupil. The diagnosis of congenital neuroblastoma was subsequently established in both infants. CONCLUSIONS: The close association of these conditions in these two young children supports the concept of a common neural crest abnormality being present. A careful systemic evaluation to rule out congenital neuroblastoma should be performed in any young child who presents with tonic pupil in the setting of central hypoventilation syndrome and Hirschsprung disease.

Adrenal Gland Neoplasms↗
PubMed2000

Inducible nitric oxide synthase inhibitors of Chinese herbs. Part 2: naturally occurring furanocoumarins.

Inducible nitric oxide synthase (iNOS)-dependent production of nitric oxide (NO) plays an important role in inflammation. The effects of various naturally occurring furanocoumarins on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage cells were evaluated in vitro. The results showed that angelicin, pimpinellin, sphondin, byakangelicol, oxypeucedanin, oxypeucedanin hydrate, xanthotoxin, and cnidilin are potential NO production inhibitors, and their IC50 values for inhibition of nitrite production were 19.5, 15.6, 9.8, 16.9, 16.8, 15.8, 16.6, and 17.7 microg/mL, respectively. Distinct structure-activity relationships were also revealed for the NO production inhibitory activities of these furanocoumarins. Activities of the angelicin type such as pimpinellin and sphondin were more potent than those of the psoralen type. Presence of a methoxy at the C6 position in the angelicin type seemed to be essential to augment the activity. Western blot analysis demonstrated that only sphondin dose-dependently inhibited the expression of the iNOS protein at 2.5-20 microg/mL. However, iNOS enzyme activity was stimulated with LPS for 12 h and sphondin was administered (20 microg/mL) for 24 h, which did not reasonably inhibit iNOS enzyme activity. L-NAME (100 microM), a known specific inhibitor of iNOS, was employed as a positive control with the same protocol and showed more than 50% inhibition activity. The results demonstrate that the NO production inhibitory activity of sphondin is due to the effect of iNOS expression, but not by direct inhibition of iNOS enzyme activity. Thus, sphondin may act as a potent inhibitor of NO production under tissue-damaging inflammatory conditions.

Animals↗
PubMed2000

Drug utilization pattern of antiepileptic drugs and traditional Chinese medicines in a general hospital in Taiwan - a pharmaco-epidemiologic study.

OBJECTIVE: Studies on antiepileptic drug utilization are important for the optimization of drug therapy and drug control. The present study was to evaluate the drug utilization pattern of standard antiepileptic drugs and traditional Chinese medicines (TCMs) in the treatment of different types of epilepsy in a general hospital in Taiwan. METHOD: The epileptic patients under antiepileptic drug treatment at Veterans General Hospital-Taipei were considered in the analysis. Current diagnosis was obtained by the neurologist in charge of the patient. All patients were interviewed by standard questionnaire designed to provide specific information on the types of antiepileptic drugs and details of their use. The questionnaire also sought to determine whether TCMs were used, and whether patients were using TCMs in combination with hospital standard treatment. The results were analysed by descriptive statistics. RESULTS: 729 patients with epilepsy definitely diagnosed were analysed in the study. 445 patients (61.04%) were prescribed with one antiepileptic drug. Combinations of two antiepileptic drugs were prescribed to 261 patients (35.80%), and combinations of three or more antiepileptic drugs to 23 patients (3.16%). A total of 1039 antiepileptic drugs was prescribed, corresponding to an average 1.42 drugs per patient. The most frequently prescribed antiepileptic drug was carbamazepine (56.93%), followed by phenytoin (31.96%), valproate (30.73%) and clonazepam (14.13%). Among the 729 epileptic patients, 83.68% used standard antiepileptic drugs alone, 16.32% used antiepileptic drugs in combination with TCMs. CONCLUSION: Monotherapy is the type of therapy most frequently used in all types of seizures. The selection of antiepileptic drugs is based on efficacy for specific seizure types and epileptic syndromes. The most frequently prescribed antiepileptic drug was carbamazepine, followed by phenytoin, valproate and clonazepam. As some of the patients used TCMs for treatment of epilepsy even when scientific medicine has been provided, further studies on the possible interactions between TCMs and antiepileptic drugs are in progress.

Adult↗
PubMed2000

Lack of pharmacokinetic interaction between valproic acid and a traditional Chinese medicine, Paeoniae Radix, in healthy volunteers.

BACKGROUND AND OBJECTIVE: In addition to the standard antiepileptic drugs, traditional Chinese medicines (TCMs) are used for the treatment of epilepsy in oriental countries. The interactions between antiepileptic drugs and TCMs represent a potential problem in clinical application. Because valproic acid (VPA), one of the most widely prescribed antiepileptic drugs, may be administered concomitantly with Paeoniae Radix (PR), one of the famous TCMs, in some epileptic patients, the present study was conducted to evaluate the influences of PR on the pharmacokinetics of VPA. METHOD: The pharmacokinetics of VPA were investigated in a randomized, open-label, two-way crossover study. Six healthy volunteers received the following treatments in a crossover design: (i) 1.2 g extract powder of Paeoniae Radix once daily for 7 days and one 200 mg VPA gastro-resistant tablet on day 7 and (ii) one 200 mg VPA gastro-resistant tablet alone on day 7. Serial plasma samples were obtained on day 7. Total and free (unbound) VPA plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). Safety measures included laboratory tests (haematology, serum chemistry and urinalysis) and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test. RESULTS: Overall clinical safety was satisfactory. The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration of VPA alone and 3-4 h after oral administration of VPA in combination with PR. The plasma level of VPA declined with a half-life of 11.71 and 11.91 h, respectively. No statistically significant difference was obtained in any of the pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2, MRT, CL/F and Vd/F) of VPA between the two treatments. Also, there was no significant difference in the protein binding rates of VPA. CONCLUSION: PR did not significantly affect the absorption, distribution, metabolism and elimination of VPA in healthy volunteers.

Administration, Oral↗