Biomedical subjects

Pei-Dawn Lee Chao

Publications and source records attributed to Pei-Dawn Lee Chao.

18 recordsLinked to original sources

PubMed2006

Morin promotes the production of Th2 cytokine by modulating bone marrow-derived dendritic cells.

Our previous studies had reported that morin decreased the interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production in lipopolysaccharide (LPS)-activated macrophages, suggesting that morin may promote helper T type 2 (Th2) response in vivo. Dendritic cells (DCs) are the most potent antigen presenting cells and known to play a major role in the differentiation of helper T type 1 (Th1) and Th2 responses. This study aimed to reveal whether morin is able to control the Th differentiation through modulating the maturation and functions of DCs. Bone marrow-derived dendritic cells (BM-DCs) were incubated with various concentrations of morin and their characteristics were studied. The results indicated that morin significantly affects the phenotype and cytokine expression of BM-DCs. Morin reduced the production of IL-12 and TNF-alpha in BM-DCs, in response to LPS stimulation. In addition, the proliferative response of stimulated alloreactive T cells was significantly decreased by morin in BM-DCs. Furthermore, allogeneic T cells secreted higher IL-4 and lower IFN-gamma in response to morin in BM-DCs. In conclusion, these results suggested that morin favors Th2 cell differentiation through modulating the maturation and function of BM-DCs.

Animals↗

PubMed2006

Ginger significantly decreased the oral bioavailability of cyclosporine in rats.

Ginger (roots of Zingiber officinale ROSCOE) is a popular spice and herbal medicine worldwide. Cyclosporine is clinically used as an important immunosupressant with narrow therapeutic index. This study attempted to investigate the effect of ginger juice on the pharmacokinetics of cyclosporine in rats. Rats were orally administered cyclosporine alone and in combination with ginger juice (5 ml/kg) concomitantly, as well as 2 hours after the ginger juice, respectively, in crossover designs. In addition, rats were intravenously administered cyclosporine with and without an oral dose of ginger juice (5 ml/kg). The blood samples were withdrawn via cardiopuncture at determined time points and cyclosporine concentrations were determined by a specific monoclonal fluorescence polarization immunoassay. The pharmacokinetic parameters of cyclosporine were calculated using a non-compartment model of WINNONLIN. The results indicated that concomitant intake of ginger significantly decreased C(max) and AUC(0-t) of oral cyclosporine by 70.9% and 63.1%, respectively. The intake of ginger 2 hours before cyclosporine significantly decreased C(max) and AUC(0-t) by 51.4% and 40.3%, respectively. In contrast, the pharmacokinetics of intravenous cyclosporine not altered by orally in combination with ginger juice. In conclusion, ginger significantly decreased the oral bioavailability of cyclosporine, and the interaction should occur at the absorption phase. Patients treated with cyclosporine should be discouraged from using ginger products to ensure the efficacy of cyclosporine.

Administration, Oral↗

PubMed2005

Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis.

Lung cancer is the leading cause of cancer death in many developed countries, including Taiwan. Quercetin, a widely distributed bioflavonoid, is well known to induce growth inhibition in a variety of human cancer cells. Quercetin glucuronides are the main circulating metabolites after dietary supplements with quercetin in humans. However, there is little information available as to how quercetin glucuronides affect human cancer cells. We investigated the effects of quercetin glucuronides in a human lung cancer cell line NCI-H209. We checked the cell viability, cell cycle checkpoint proteins, pro- and antiapoptotic proteins, caspase-3 activity, and gene expression by flow cytometry and Western blot. The viability of cells decreased in a dose- and time-dependent manner. Cell cycle analysis revealed a significant increase of the proportion of cells in G2/M phase and subG0/G1 phase (corresponding to apoptotic cells). Moreover, quercetin glucuronides increased the expressions of cyclin B, Cdc25c-ser-216-p, and Wee1 proteins, indicating the G2/M arrest. We also demonstrated a concurrent decrease of the mitochondrial membrane potential, release of cytochrome c, up-regulation of Bax, down-regulation of Bcl-2, and activation of caspase-3, and subsequently, cleavage of poly(ADP-ribose) polymerase. In addition, quercetin glucuronide-induced apoptosis was totally blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone. Taken together, we demonstrated that quercetin glucuronides inhibited proliferation through G2/M arrest of the cell cycle and induced apoptosis via caspase-3 cascade in the human lung cancer cell line NCI-H209. Delineation of the biological effects of specific major quercetin metabolites on chemotherapeutic potential or chemoprevention of human cancers warrants further investigation.

Animals↗

PubMed2005

Inhibition of iNOS gene expression by quercetin is mediated by the inhibition of IkappaB kinase, nuclear factor-kappa B and STAT1, and depends on heme oxygenase-1 induction in mouse BV-2 microglia.

In the present study, experiments were performed to explore the action of quercetin, the most widely distributed flavonoids, and its major metabolite, quercetin-3'-sulfate, on lipopolysaccharide (LPS)- and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) production in BV-2 microglia. Quercetin could suppress LPS- and IFN-gamma-induced NO production and inducible nitric oxide synthase (iNOS) gene transcription, while quercetin-3'-sulfate had no effect. LPS-induced IkappaB kinase (IKK), nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation, and IFN-gamma-induced NF-kappaB, signal transducer and activator of transcription-1 (STAT1) and interferon regulatory factor-1 (IRF-1) activation were reduced by quercetin. Moreover quercetin was able to induce heme oxygenase-1 expression. To address the involvement of heme oxygenase-1 induction in iNOS inhibition, heme oxygenase-1 antisense oligodeoxynucleotide was used. Quercetin-mediated inhibition of NO production and iNOS protein expression were partially reversed by heme oxygenase-1 antisense oligodeoxynucleotide, but was mimicked by hemin, a heme oxygenase-1 inducer. The involvement of signal pathways in quercetin-induced heme oxygenase-1 gene expression was associated with tyrosine kinase and mitogen-activated protein kinases activation. All these results suggest quercetin should provide therapeutic benefits for suppression of inflammatory-related neuronal injury in neurodegenerative diseases.

Amides↗

PubMed2005

Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats.

Isoflavone supplements are nowadays widely used as alternative for hormone replacement therapy. However, the safety remains unanswered. This study attempted to investigate the effect of Pueraria lobata root decoction (PLRD), an isoflavone-rich herb, on the pharmacokinetics of methotrexate (MTX), a bicarboxylate antimetabolite with narrow therapeutic window. Rats were orally and intravenously given methotrexate alone and coadministered with PLRD. Blood samples were withdrawn via cardiopuncture at specific time points after drug administration. Serum methotrexate concentrations were assayed by specific monoclonal fluorescence polarization immunoassay method. Pharmacokinetic parameters were calculated using noncompartment model of WINNONLIN for both oral and intravenous data of MTX. Our results showed that coadministration of 4.0 g/kg and 2.0 g/kg of PLRD significantly increased the AUC(0-t) by 207.8% and 127.9%, prolonged the mean residence time (MRT) by 237.8 and 155.2%, respectively, finally resulted in surprisingly high mortalities of 57.1% and 14.3% in rats. When MTX was given intravenously, the coadministration of PLRD at 4.0 g/kg significantly increased the half-life by 53.9% and decreased the clearance by 47.9%. In conclusion, the coadministration of PLRD significantly decreased the elimination and resulted in markedly increased exposure of MTX in rats.

Administration, Oral↗

PubMed2005

Pharmacokinetic and pharmacodynamic interactions of morin and cyclosporin.

Morin is a flavonoid present in mulberry and herbs. We have reported that morin exerted anti-inflammatory activity on the activated macrophages. Cyclosporin (CsA) is a potent immunosuppressive agent with narrow therapeutic range, which is widely used for the treatments of autoimmune diseases and transplantation rejection. This study aimed to measure the effects of morin on the disposition of CsA in lymphoid and non-lymphoid tissues, and on the functions of immune cells in mice. CsA (Neoral, 10 mg/kg) was orally administered with and without a concomitant dose of morin (0, 50, 100, 200 mg/kg) to mice once daily for 2 weeks. CsA concentrations in blood, liver, kidney, and spleen were determined by a specific monoclonal fluorescence polarization immunoassay. The decreased levels of CsA in tissues were found well correlated to increased doses of morin. The coadministration of 200 mg/kg morin significantly decreased CsA in blood, liver, kidney, and spleen by 33%, 17%, 38%, and 45%, respectively. On the other hand, coadministration of morin decreased dramatically the nitric oxide production by the activated macrophages when compared to CsA treatment alone. Moreover, morin maintained the level of CsA-suppressed T helper 1 (Th1) type cytokine, although the CsA concentration in spleen was markedly reduced. In conclusion, morin coadministration profoundly reduced CsA concentration but did not significantly alter the CsA-suppressed Th1 immune response in mice.

Animals↗

PubMed2005

Profound difference of metabolic pharmacokinetics between pure glycyrrhizin and glycyrrhizin in licorice decoction.

To investigate the difference of metabolic pharmacokinetics between pure glycyrrhizin (GZ) and GZ in licorice decoction, six New Zealand White rabbits were orally given pure GZ and licorice decoction containing equivalent content of GZ in a randomized crossover design. HPLC methods were used for the quantitation of GZ and glycyrrhetic acid (GA) in serum. The results indicated that the areas under curves (AUCs) of GZ and GA after administration of licorice decoction were significantly higher than those after pure GZ. This result was contradictory with that obtained in rats. To explore the mechanism of the pharmacokinetic difference, feces of rabbits, rats, pigs and humans were used to investigate the presystemic metabolism of pure GZ and GZ in licorice decoction. The results indicated that pure GZ was hydrolyzed to GA more rapidly and to a greater extent than that in licorice decoction by various feces. In addition, when pure GZ was fermented, the metabolic profiles of GA and 3-dehydroGA in rabbit feces were quite different from other feces. In conclusion, the bioavailabilities of GZ and GA are significantly better from licorice than from pure GZ in rabbits but the presystemic metabolism of pure GZ in rabbit is rather different from that in rat, pig and human.

Animals↗

PubMed2005

Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds.

The 3C-like protease (3CLpro) of SARS-coronavirus mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, becoming an important target for the drug development. In this study, Isatis indigotica root extract, five major compounds of I. indigotica root, and seven plant-derived phenolic compounds were tested for anti-SARS-CoV 3CLpro effects using cell-free and cell-based cleavage assays. Cleavage assays with the 3CLpro demonstrated that IC50 values were in micromolar ranges for I. indigotica root extract, indigo, sinigrin, aloe emodin and hesperetin. Sinigrin (IC50: 217 microM) was more efficient in blocking the cleavage processing of the 3CLpro than indigo (IC50: 752 microM) and beta-sitosterol (IC50: 1210 microM) in the cell-based assay. Only two phenolic compounds aloe emodin and hesperetin dose-dependently inhibited cleavage activity of the 3CLpro, in which the IC50 was 366 microM for aloe emodin and 8.3 microM for hesperetin in the cell-based assay.

Animals↗

PubMed2004

Significant decrease of cyclosporine bioavailability in rats caused by a decoction of the roots of Scutellaria baicalensis.

Scutellariae Radix (SR), the root of Scutellaria baicalensis (Labiatae), is widely used in clinical Chinese medicine. In order to investigate the effect of SR on the absorption and disposition of cyclosporine, rats were administered with cyclosporine orally (in the form of the microemulsion Neoral and intravenously with and without coadministration of SR decoction in randomized cross-over designs, respectively. Furthermore, the effects of the major constituents, e. g., baicalin and its aglycone baicalein on cyclosporine pharmacokinetics were also investigated in rats. A specific monoclonal fluorescence polarization immunoassay was used to determine the blood concentration of cyclosporine. Our results indicated that coadministration of SR decoction at doses of 1 g/kg and 2 g/kg significantly decreased the C (max) of cyclosporine by 62.9 % and 79.6 % and reduced the AUC (0 - 540) by 55.2 % and 82.0 %, respectively. On the contrary, coadministration of baicalin and baicalein at doses of 112 micromol/kg markedly elevated the C (max) of cyclosporine by 408.1 % and 87.5 % and increased the AUC (0 - 540) by 685.3 % and 150.2 %, respectively. Nevertheless, SR decoction did not alter the pharmacokinetics of intravenous cyclosporine. These results indicate that a profound interaction between SR decoction and cyclosporine occurred at the absorption site. In order to ensure the efficacy and safety of cyclosporine, the coadministration of SR and its preparations with oral cyclosporine should be avoided.

Animals↗

PubMed2003

Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock.

Morin is a flavonoid present in fruits and Chinese herbs. Based on in vitro studies, morin has been reported to show various beneficial biological activities. However, there is growing evidence that conjugative metabolism is central to the biological fate of flavonoids. Therefore, the biological effects of morin could be primarily determined by its conjugated metabolites. In this study, the effects of morin and its sulfates/glucuronides on the production of nitric oxide (NO) and cytokines from lipopolysaccharide (LPS)-activated macrophages were individually investigated and compared. The results indicated that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by 1.25 mM morin and 1.25 microM morin sulfates/glucuronides. Meanwhile, the 50% inhibition concentration (IC50) values of morin and morin sulfates/glucuronides in activated peritoneal macrophages were 1.5 mM morin and 1.5 microM morin sulfates/glucuronides, respectively. In addition, 30% of the tumor necrosis factor-alpha (TNF-alpha) and 35% of the interleukin (IL)-12 productions from activated macrophages were inhibited by 2-2.5 mM morin and 2-2.5 microM morin sulfates/glucuronides, respectively. Furthermore, phagocyte activities in the peripheral blood of those for mice dosed with morin for two months were about 65-70% of controls. Lower NO production and reduced macrophage phagocytic activities corresponded to LPS-resistant state. These findings indicated that morin may exhibit anti-inflammatory activity and reduced the incidence of experimental septic shock through decreasing the functions of macrophages and may regulate immune response through modulating the cytokine profiles. Therefore, morin could be a promising therapeutic candidate for inflammatory disease due to the strong activity of its metabolites.

Animals↗

PubMed2003

A deglucosylated metabolite of paeoniflorin of the root of Paeonia lactiflora and its pharmacokinetics in rats.

Paeoniflorin is a bioactive monoterpene glucoside in Paeoniae Radix (PR), the roots of Paeonia lactiflora (Ranunculaceae). By oral administration to rats with the decoction of PR, the metabolism and pharmacokinetics of paeoniflorin were investigated in this study. A deglucosylated metabolite of paeoniflorin, paeoniflorgenin (PG), in serum was identified based on HPLC/MS and NMR spectral data. HPLC/UV methods were developed for determining PG in serum and feces suspension. A non-compartment model was used for the calculation of pharmacokinetic parameters. Moreover, the metabolism of paeoniflorin by various types of feces was investigated as well. The paeoniflorin levels in serum were below the detection limit throughout the study. The C (max), t (max), and AUC (0-t) of PG were 8.0 microg/mL, 10 min and 487.0 microg min/mL, respectively. Paeoniflorin was found to be hydrolyzed into PG through incubation with feces of rabbit, rat, pig or human. Similar profiles of PG were shown for various types of feces, except for rabbit. In conclusion, paeoniflorin was not absorbed per se, whereas its aglycone paeoniflorgenin was absorbable and circulating in the bloodstream. Rat and pig are appropriate models for investigating the metabolism and pharmacokinetics of paeoniflorin.

Administration, Oral↗

PubMed2003

Comparison of metabolic pharmacokinetics of baicalin and baicalein in rats.

Baicalin and baicalein, a flavone glucuronide and its aglycone, are bioactive constituents of Scutellariae Radix with various beneficial activities. We have characterized and compared the metabolic pharmacokinetics of baicalin and baicalein in rats. Baicalein was administered intravenously and orally to rats, and baicalin was orally administered. An HPLC method was used to determine the concentration of baicalein before and after hydrolysis using beta-glucuronidase/sulfatase. The pharmacokinetic parameters were calculated by using WINNONLIN. Unpaired Student's t-test was used for statistical comparison. The result showed that after intravenous administration of baicalein, 75.7% of the dose was circulating as its conjugated metabolites. After oral administration of baicalein, absorption of baicalein itself was negligible, whereas the glucuronides/sulfates of baicalein were predominant in the plasma. When compared with intravenous bolus administration with dose correction, the absolute absorption was 40%. When baicalin was administered orally, glucuronides and sulfates of baicalein were exclusively circulating in the plasma. The relative absorption for baicalin was 65% when compared with baicalein. Profound differences of serum profile and pharmacokinetics were observed between oral baicalein and baicalin. Baicalin demonstrated significantly later time to peak concentration (t(max)) and lower peak serum concentration (C(max)) of baicalein conjugated metabolites than baicalein, indicating baicalin was absorbed more slowly and to a lesser extent than baicalein.

Absorption↗

PubMed2003

Degradation of flavonoid aglycones by rabbit, rat and human fecal flora.

The degradation of thirteen flavonoid aglycones-wogonin, diosmetin, hesperetin, baicalein, morin, genistein, daidzein, quercetin, naringenin, luteolin, kaempferol, apigenin and neophellamuretin-were investigated in rabbit, rat and human fecal flora suspensions as well as in artificial intestinal juice, using high performance liquid chromatography. Separation were performed with a Cosmosil 5C(18)-AR II column by isocratic and gradient elution with 0.1% (v/v) phosphoric acid-acetonitrile as a mobile phase, and detected at 254 nm. The flow rate was 1.0 ml/min. 5,7-Dimethoxycoumarin was used as the internal standard. The result indicated that all flavonoid aglycones except baicalein, diosmetin and quercetin were quite stable in artificial intestinal juice, whereas all were degraded in rabbit, rat and human feces suspension. In rabbit feces, wogonin, diosmetin and hesperetin were less degraded, whereas neophellamuretin, apigenin, kaempferol, luteolin, and naringenin were the most extensively degraded. In rat feces, wogonin and diosmetin were least degraded, whereas kaempferol, quercetin, genistein, luteolin, naringenin and neophellamuretin were extensively degraded. As in human feces, wogonin, daidzein and diosmetin were less degraded, whereas morin, genistein, baicalein, and quercetin were extensively degraded. In conclusion, wogonin and diosmetin were among the less degraded ones for all three feces tested. The presence of a methoxy group on the A or B ring of the flavonoid seems to protect the structure from bacterial degradation.

Animals↗

PubMed2003

Urinary pharmacokinetics of baicalein, wogonin and their glycosides after oral administration of Scutellariae Radix in humans.

Baicalin, baicalein, wogonoside and wogonin are flavone constituents of Scutellariae Radix with various beneficial biological activities. The purpose of this study was to investigate the urinary pharmacokinetics of these flavones after oral administration of Scutellariae Radix commercial powder. Ten healthy male volunteers received a dose of 5.2 g commercial powder (comparable to 9 g crude drug), respectively. The concentrations of baicalin, baicalein and wogonin in the commercial powder as well as their metabolites in urine were assayed by HPLC method. The glucuronides and sulfates of baicalein and wogonin in urine were hydrolyzed with beta-glucuronidase and sulfatase, respectively. Our results showed that the mean cumulated renal excretion of baicalein glucuronides and sulfates were 43.1+/-4.5 micromol (2.9% of dose) and 64.8+/-6.3 micromol (4.3% of dose), respectively, whereas wogonin glucuronides and sulfates were 21.6+/-2.0 micromol (5.9% of dose) and 20.7+/-1.7 micromol (5.7% of dose), respectively. The result indicated that the renal excretion of conjugated metabolites of wogonin (11.6% of dose) were higher than that of baicalein (7.2% of dose). The baicalein sulfates was predominant than the corresponding glucuronides, whereas wogonin sulfates was comparable to the corresponding glucuronides.

Administration, Oral↗

PubMed2002

Comparison of metabolic pharmacokinetics of naringin and naringenin in rabbits.

Naringin and naringenin are antioxidant constituents of many Citrus fruits. Naringenin is the aglycone and a metabolite of naringin. In order to characterize and compare the metabolic pharmacokinetics of naringenin and naringin, naringenin was administered intravenously and orally to rabbits, and naringin was administered orally. The concentration of naringenin in serum prior to and after enzymatic hydrolysis was determined by HPLC method. The pharmacokinetic parameters were calculated by using WINNONLIN. The results showed that the absolute bioavailability of oral naringenin was only 4%, whereas after taking the conjugated naringenin into account, it increased to 8%. When naringin was administered orally, only little naringenin and predominantly its glucuronides/sulfates were circulating in the plasma. The ratio of AUC of naringenin conjugates to the total naringenin absorbed into the systemic circulation after oral naringenin was much higher when compared to that after i.v. bolus of naringenin, indicating that extensive glucuronidation/sulfation of naringenin occurred during the first pass at gut wall. Oral dosing of naringin resulted in even higher ratio of AUC of naringenin conjugates to the total naringenin than that after oral naringenin. Our results also showed that there were great differences in pharmacokinetics of naringin and naringenin. Oral naringin resulted in latter Tmax, lower Cmax and longer MRT (mean residence time) for both naringenin and its conjugated metabolites than those after oral naringenin.

Administration, Oral↗

PubMed2002

Delocalized electronic structure of the thiol sulfur substantially prevents nucleic acid damage induced by neocarzinostatin.

Neocarzinostatin is a potent antitumor antibiotic and is a prodrug, which induces genome damage after activation by a thiol. The prodrug is stored as a protein-bound chromophore that contains an enediyne nucleus. A thiolate attack on the chromophore cyclizes the nucleus and produces radicals that abstract hydrogen from DNA. Because thiol is the only cofactor in the vital activation process, the structure of the thiol plays an important role in the activity of the drug. Here we systematically examine the effect of the electronic structure of some thiols on the efficiency of the drug, and compare particularly aromatic with aliphatic thiols. The values of drug-induced base release from DNA are remarkably different between thiophenol (3.6%) and benzyl mercaptan (12.5%), the activity of which is comparable with those of aliphatic thiols. Cleavage results determined by DNA electrophoresis are consistent with the results of base release; they show that the total number of DNA lesions is more than 3-fold lower for thiophenol than for aliphatic thiols or benzyl mercaptan. We conclude that among aromatic thiols, only those that have delocalized thiol sulfur electrons can substantially reduce the DNA cleavage activity. This result suggests that the effect of an aromatic ring arises from an inductive effect imposed on the thiol sulfur electron through pi-resonance rather than through effects such as aromatic stacking, steric hindrance, or hydrophobic interaction. Replacing thiophenol with substituted derivatives with electron-releasing or -withdrawing groups changes the drug activity and supports the important role of the electronic structure of the thiol sulfur in determining the drug activity.

Acetylcysteine↗

PubMed2002

Marked decrease of cyclosporin absorption caused by phellamurin in rats.

Phellamurin is a flavonoid glycoside that is abundant in the leaves of Phellodendron wilsonii Hayata et Kanehira (Rutaceae). In vitro everted rat intestine study indicated that phellamurin inhibited intestinal P-glycoprotein in a dose-dependent manner. In order to investigate the effect of phellamurin on cyclosporin absorption and disposition, rats were given cyclosporin (5 mg/kg) with or without phellamurin in a parallel design. Fluorescence polarization immunoassay was used to determine the blood concentration of cyclosporin. Unanticipatedly, our results indicated that the coadministration of phellamurin significantly decreased the Cmax of cyclosporin by 77 % and reduced the AUC(0-infinity) of cyclosporin by 56 %. This indicated that a serious interaction occurred between phellamurin with cyclosporin. To ensure the efficacy of cyclosporin, we suggest that the coadministration of phellamurin or Phellodendron wilsonii with cyclosporin should be avoided.

Animals↗

PubMed2002

Influence of honey on the gastrointestinal metabolism and disposition of glycyrrhizin and glycyrrhetic acid in rabbits.

To investigate the effects of honey on the pharmacokinetics of glycyrrhizin and glycyrrhetic acid, administration of glycyrrhizin or glycyrrhetic acid with and without honey was carried out in rabbits in a randomized crossover design. An in vitro study using rabbit fecal flora was employed to elucidate the mechanism of the interaction. HPLC methods were used for the determination of glycyrrhizin, glycyrrhetic acid and 3-dehydroglycyrrhetic acid concentrations in serum and feces. Paired and unpaired Student's t-tests were used for statistical comparisons for in vivo and in vitro studies, respectively. Our study indicated that the area under the curve (AUC0-t) of glycyrrhetic acid was significantly enhanced by 53% when honey was concomitantly given with glycyrrhizin, whereas that of glycyrrhizin was not significantly altered. Nevertheless, lack of effect was observed when honey was concurrently given with glycyrrhetic acid. Fecal study indicated that both the hydrolysis of glycyrrhizin to glycyrrhetic acid and subsequent oxidation of glycyrrhetic acid to 3-dehydroglycyrrhetic acid were significantly affected in the presence of honey to result in more glycyrrhetic acid available for absorption. It could be concluded that honey significantly affected the gastrointestinal metabolism of glycyrrhizin and resulted in the increased glycyrrhetic acid exposure. Therefore, honey might enhance the efficacy and adverse effects of glycyrrhizin.

Animals↗