Ryu, Jae Sik;Lee, Hyun Jung;Bae, Song Hwan;Kim, Sun Young;Park, Yooheon;Suh, Hyung Joo;Jeong, Yoon Hwa
Journal of Ginseng Research
/
제37권1호
/
pp.108-116
/
2013
For the improvement of ginsenoside bioavailability, the ginsenosides of fermented red ginseng by Phellinus linteus (FRG) were examined with respect to bioavailability and physiological activity. The polyphenol content of FRG ($19.14{\pm}0.50$ mg/g) was significantly higher (p<0.05) compared with that of non-fermented red ginseng (NFRG, $11.31{\pm}1.15$ mg/g). The antioxidant activities in FRG, such as 2,2'-diphenyl-1-picrylhydrazyl, 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid, and ferric reducing antioxidant power, were significantly higher (p<0.05) than those in NFRG. The HPLC analysis results showed that the FRG had a high level of ginsenoside metabolites. The total ginsenoside contents in NFRG and FRG were $41.65{\pm}1.53$ mg/g and $50.12{\pm}1.43$ mg/g, respectively. However, FRG had a significantly higher content ($33.90{\pm}0.97$ mg/g) of ginsenoside metabolites (Rg3, Rg5, Rk1, compound K, Rh1, F2, and Rg2) compared with NFRG ($14.75{\pm}0.46$ mg/g). The skin permeability of FRG was higher than that of NFRG using Franz diffusion cell models. In particular, after 3 h, the skin permeability of FRG was significantly higher (p<0.05) than that of NFRG. Using a rat everted intestinal sac model, FRG showed a high transport level compared with NFRG after 1 h. FRG had dramatically improved bioavailability compared with NFRG as indicated by skin permeation and intestinal permeability. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).
In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).
The pharmacokinetics and bioavailability of ambroxol, an expectoration improver and mucolytic agent, were studied to determine the feasibility of enhanced transdermal delivery of ambroxol from the ethylene-vinyl acetate (EVA) matrix system containing polyoxyethylene-2-oleyl ether as an enhancer in rats. The ambroxol-010 matrix system (15 mg/kg) was applied to abdominal skin of rats. Blood samples were collected via the femoral artery for 28 hrs and the plasma concentrations of ambroxol were determined by HPLC. Pharmacokinetic parameters were calculated using Lagran method computer program. The area under the curve (AUC) was significantly higher in the enhancer group ($1,678{\pm}1,413.3\;ng/ml{\cdot}hr$) than that in the control group $1,112{\pm}279\;ng/ml{\cdot}hr$), that is treated transdermally without enhancer, showing about 151% increased bioavailability (p<0.05). The average $C_{max}$ was increased in the enhancer group ($86.0{\pm}21.5\;ng$/ml) compared with the control group ($59.0{\pm}14.8\;ng$/ml). The absolute bioavailability was 13.9% in the transdermal control group, 21.1% in the transdermal enhancer group and 18.1% in the oral administration group compared with the IV group. The $T_{max}$, $K_a$, MRT and $t_{1/2}$ of ambroxol in transdermal enhancer group were increased significantly (p<0.01) compared to those of oral administration. As the ambroxol-EVA matrix containing polyoxyethylene-2-oleyl ether and tributyl citrate was administered to rats via the transdermal routes, the relative bioavailability increased about 1.51-fold compared to the control group, showing a relatively constant, sustained blood concentration. The results of this study show that ambroxol-EVA matrix could be developed as a transdermal delivery system providing sustained plasma concentration.
In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.
In order to investigate the extent and degree of arsenic and heavy metal contamination and the bioavailability of toxic elements around the abandoned mine in Korea, an environmental geochemical survey was undertaken in the Daduk mine. After appropriate preparation, tailings, soil, stream sediment, crop plant and fingernail samples were analysed for As, Cd, Cu, Pb and Zn by ICP-AES and ICP-MS. Elevated levels of 8,782 mg/kg As, 8.3 mg/kg Cd, 489 mg/kg Cu, 3,638 mg/kg Pb and 919 mg/kg Zn were found in tailings from the Daduk mine. These significant concentrations can impact on soils and sediments around the tailing ponds. Mean concentrations of As, Cd, Pb, Cu and Zn in soils are significantly higher than those in world average soil, especially for As and Pb. Element concentrations in sediments decrease with distance from the tailing ponds due to a dilution effect by the mixing of uncontaminated sediments. Arsenic and Cd are elevated in rice grains and stalks, and Cu and Zn concentrations in chinese cabbage, sesame and bean leaves are higher than the upper limit values for normal plant. Arsenic concentration in fingernails of farmers are higher than the normal level with a maximum value of 1.5 mg/kg. The post-ingestion bioavailability of toxic heavy metals in some paddy and farmland soils has been also investigated using the SBET (simple bioavailability extract test) method. The method utilises synthetic leaching fluids closelyanalogous to those of the human stomach. The quantities of As, Cd, Cu, Pb and Zn extracted from paddy soils after 1 hour indicated 15.9, 65.4, 46.2, 39.4 and 29.4% bioavailability, respectively and for farmland soils, 12.4, 26.0, 31.2, 29.3 and 19.4% bioavailability, respectively. The results of the SBET indicate that regular ingestion of soils by the local population could pose a potential health threat due to long-term toxic element exposure.
The purpose of this study was to investigate the effect of naringin pretreatment on the bioavailability and phar-macokinetics of diltiazem and one of its metabolites, deacetyldiltiazem, in rabbits. Pharmacokinetic parameters of diltiazem and deacetyldiltiazem were determined after oral administration of diltiazem (15 mg/kg) pretreated with naringin (1.5, 7.5 and 15 mg/kg). Absorption rate constant ($k_a$) of diltiazem after oral administration of diltiazem pretreated with naringin was significantly (p<0.05 or p<0.0l) increased compared to the control group. Area under the plasma concentration-time curve (AUC) and peak concentration ($C_{max}$) of the diltiazem were significantly (p<0.05 or p<0.01) higher than those of the control. Absolute bioavailability ($AB\%$) of diltiazem pretreated with naringin ranged from $13.5\%$ to $18.6\%$, being enhanced compared to that of the control, $7.2\%$. Relative bioavailability ($RB\%$) of diltiazem was $1.9\~2.6$ times higher than that of the control group. There was no significant change in terminal half-life ($t_{1/2}$) and $T_{max}$ of diltiazem in the presence of naringin. AUC of deacetyldiltiazem pretreated with naringin was significantly (p<0.05) higher than (p<0.05) that of the control. But the metabolite ratios (MR) were significantly decreased (p<0.05), implying that pretreatment of naringin could be effective to inhibit the CYP 3A4-mediated metabolism of diltiazem. In this study, pretreatment of naringin significantly enhanced the oral bioavailability of diltiazem. These results suggested that the diltiazem dosage should be adjusted when it is administered with naringin or a naringin-containing dietary supplement in the clinical setting.
Carotenoid-rich foods focus one's attention on the prevention age-related diseases. This study was conducted to investigate the carotenoid status and look into the factors that affect the bioavailability of carotenoid in 121 elderly nonsmoking Korean women. Carotenoids and lipids in plasma, and nutrient intakes including carotenoid were studied. The mean plasma total-cholesterol, HDL-cholesterol, LDL-cholesterol and triacylglycerol concentrations were 220.0 mg/dl 49.5mg/dl , 139.2mg/dl and 157.4mg/dl , respectively. Significantly positive correlations were found between the plasma lutein + zeaxanthin, lycopene and $\beta$-carotene concentrations and the intake of fruits (r=0.17, r=0.20, r=0.19). However, significantly negative correlations were found between the plasma zeaxanthin, and $\beta$-carotene concentrations that adjusted for carotenoid intakes and intakes of vegetables (r=-0.21, r=-0.19), and between plasma lutein+zeaxanthin, lycopene and $\beta$-carotene concentrations that adjusted for carotenoid intakes and intakes of fruits (r= -0.21, r=-0.18, r=-0.24). After the adjustment for plasma lipids, there was no correlation between the plasma carotenoid concentrations and the carotenoid-rich foods. However, after adjustment for fiber intake, significantly strong positive correlations were found between the plasma carotenoid concentrations and carotenoid-rich foods. The plasma levels of carotenoid biomarkers (plasma carotenoid concentrations adjusted for dietary fiber intakes) decreased with age, and the plasma levels of lycopene biomarkers (plasma lycopene concentrations adjusted for dietary fiber intakes) increased with regular exercise. However alcohol drinking had no impact. These results suggested that age, physical activity, and dietary fiber intake affected the bioavailability of carotenoid. Therefore, when the elderly have carotenoid-rich foods, they should consider ways of increasing the bioavailability of carotenoid through cooking methods and Physical activity.
Kim, Hyeongmin;Lee, Jong Hyuk;Kim, Jee Eun;Kim, Young Su;Ryu, Choong Ho;Lee, Hong Joo;Kim, Hye Min;Jeon, Hyojin;Won, Hyo-Joong;Lee, Ji-Yun;Lee, Jaehwi
Journal of Ginseng Research
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제42권3호
/
pp.361-369
/
2018
Ginsenosides, dammarane-type triterpene saponins obtained from ginseng, have been used as a natural medicine for many years in the Orient due to their various pharmacological activities. However, the therapeutic potential of ginsenosides has been largely limited by the low bioavailability of the natural products caused mainly by low aqueous solubility, poor biomembrane permeability, instability in the gastrointestinal tract, and extensive metabolism in the body. To enhance the bioavailability of ginsenosides, diverse micro-/nano-sized delivery systems such as emulsions, polymeric particles, and vesicular systems have been investigated. The delivery systems improved the bioavailability of ginsenosides by enhancing solubility, permeability, and stability of the natural products. This mini-review aims to provide comprehensive information on the micro-/nano-sized delivery systems for increasing the bioavailability of ginsenosides, which may be helpful for designing better delivery systems to maximize the versatile therapeutic potential of ginsenosides.
The purpose of this study was to investigate the effect of a cotreatment of bamboo concentrates (Jukcho solution; 0.75, 1.5, and 3.0 mL/kg) with the chemotherapeutic agent paclitaxel on the bioavailability of orally administered paclitaxel (50 mg/kg) in rats. The effect of a pretreatment of bamboo concentrates (1.5 and 3.0 mL/kg for 1.0 h or a consecutive 3 day) was also examined. The paclitaxel plasma concentrations of rats orally administered paclitaxel plus bamboo concentrates (coadministration, 3.0 mL/kg and pretreatment, 1.5 and 3.0 mL/kg) were significantly higher than those of rats treated with paclitaxel alone. Plasma concentrations of paclitaxel in groups pretreated with bamboo concentrates for 3 day were markedly higher than those of a paclitaxel control group at the measured time points. The areas under plasma concentration-time curves (AUCs) of paclitaxel in groups pretreated with bamboo concentrates were elevated and the absolute bioavailability ($AB\%$) and relative bioavailability ($RB\%$) of paclitaxel were also significantly higher than those in the control group. The peak concentration ($C_{max}$), half-life ($t_{1/2}$), and the elimination rate constant ($K_{el}$) of paclitaxel after 3 day of pretreatment with bamboo concentrates were also significantly higher than those in the control, but the time required to reach the maximum plasma concentration ($T_{max}$) of paclitaxel was unaffected by the bamooo concentrates. Western blot analyses demonstrated that the level of CYP3A4 was increased in the livers of rats treated orally with paclitaxel, but this was reversed by pretreating with bamboo concentrates. These results show that bamboo concentrates enhance the bioavailability of orally administered paclitaxel and this effect may be associated with a diminished expression of CYP3A4 in the liver.
To increase both iron and enhancers for iron absorption through diets should be a basic strategy to sufficiently provide increased iron for pregnancy. Previous studies reported that iron intakes of Korean pregnant women were short and their iron status deteriorated as pregnancy progressed. However, there is little data about the bioavailability of dietary iron during pregnancy. Therefore, this study was conducted to determine the changes of dietary iron intakes, its bioavailability and iron status during pregnancy longitudinally in Korean women. A total of 151 pregnant women in their first trimester of pregnancy voluntarily participated. Among them, 72 women finished the research protocol during the second trimester and 55 did it during the third trimester. Dietary intakes of total iron, both non-heme and heme iron, as well as enhancers, both MPF (meat, poulty, and fish) and vitamin C, increased significantly as pregnancy progressed. As the results, bioavailability of dietary iron and iron absorbed increased significantly as pregnancy progressed. However, the amount of iron absorbed at each trimester did not meet considerably the iron needed during pregnancy. All five indices examined in the study, Hb level, Hct, serum concentrations of ferritin and sTfR (soluble transferrin receptor), and sTfR: ferritin ratio, showed that iron status of the subjects deteriorated as pregnancy progressed. The rate of anemia of the subjects increased as pregnancy progressed although more than 80% of the subjects took iron supplements after the 20th week of pregnancy. These results imply that it is needed to provide more iron especially, heme iron and dietary enhancers to prevent the deterioration of iron status during pregnancy. Future research on bioavailability of supplemental iron should be performed to determine the iron balance precisely.
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