Diosgenin, found in wild yam (Dioscorea villosa), has been shown to ameliorate diabetes and hyperlipidemia, increase cell proliferation in a human 3D skin model, and inhibits melanin production in B16 melanoma cells. It is also an active element in cosmeceutical and dietary supplements. Although the bioavailability of diosgenin is low due to its poor solubility and intestinal permeability, it was subsequently improved using a β-cyclodextrin (β-CD) inclusion complex. Recently liquid crystals (LCs) were shown to enhance the bioavailability of poorly water-soluble drugs. The purpose in the present study was to prepare diosgenin LCs and investigate the interaction between LC and β-CD in order to improve its bioavailability of diosgenin. Crystallinity and particle diameters of LCs in water were determined by small angle X-ray scattering (SAXS) and Zetasizer. Pharmacokinetic parameters were calculated using the plasma content of diosgenin after its oral administration to Wistar rats. Regarding the formation of glyceryl monooleate (GMO) and phytantriol (PHY) LC, SAXS patterns showed the hexagonal and cubic phases, respectively. Bioavailability was significantly enhanced after oral administration of LCs prepared by GMO than after diosgenin alone. The bioavailability was further improved with the combination of LC and β-CD than LC and water.

Orally administrated diosgenin, a steroidal saponin found in several plants including Dioscorea villosa, recovers skin thickness reduced in ovariectomized mice, and plays an important role in the treatment of hyperlipidemia. Thus, diosgenin is an active element of cosmeceutical and dietary supplements. However, we have already elucidated that the skin distribution and absolute oral bioavailability of diosgenin is very low. The aim of this study is to evaluate the efficacy of diosgenin-cyclodextrin (CD) complexes in improving the skin concentration of diosgenin. The formation of the CD complex was indicated by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscope (SEM) studies. Oral administration of the diosgenin/β-CD complex resulted in a significant enhancement in terms of the skin distribution of diosgenin, maximum plasma level (C max ), area under the plasma concentration-time curve (AUC), and absolute oral bioavailability over those of the drug alone. These results suggest that the inclusion complex of diosgenin/β-CD can be used to improve low skin content of diosgenin.

Orally administrated diosgenin, a steroidal saponin found in the roots of Dioscorea villosa, improves reduced skin thickness in ovariectomized mice, and plays an important role in the treatment of hyperlipidemia. Diosgenin has been noticed as an active element in cosmeceutical and dietary supplements. We have already elucidated that the absolute oral bioavailability of diosgenin is very low; however, a high skin distribution of diosgenin was also observed. The aim of the present study was to examine and compare the effects of β-cyclodextrin (β-CD) and 3 kinds of its derivatives such as hydroxypropyl β-CD on the diosgenin permeability using a Caco-2 model and rat jejunal perfusion. These derivatives of β-CD greatly improved the low solubility of diosgenin. No significant increase was observed in the lactate dehydrogenase leakage from Caco-2 cell, while a slight decrease was found on the transepithelial electrical resistance by diosgenin and β-CD derivatives. However, β-CD derivatives, especially hydroxyethyl β-CD and hydroxypropyl β-CD, markedly enhanced diosgenin permeability across the Caco-2 monolayer and rat jejunum. The bioavailability of diosgenin in the presence of β-CD derivatives were about 4 to 11 fold higher than diosgenin suspension. The mechanisms of these enhancement effects may be due to improvements in solubility and tight junction opening.

Reports about the peroxisomes of rat liver are abundant, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] but much less is known about those of other rat organs. 17,18) Furthermore, there are few reports about peroxisomes of human liver, 2,3,5,6,[8][9][10]14,19) and very few about those of other human organs. [20][21][22] There are three kinds of trophoblasts in the placenta: cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts. Each of the three plays important roles in the development and maintenance of gestation. In human trophoblasts, peroxisomes are known to be present in cytotrophoblast cells, 20,22) and are detected later during gestation in syncytiotrophoblast cells. 22)However, extravillous trophoblast cells are difficult to obtain; therefore peroxisomes in these cells have not yet been elucidated.Clofibric acid (a fibric acid derivative) is a hypolipidemic agent. This agent, at least, is thought to suppress the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutarylCoA reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis in the whole body 23,24) and cell cultures.13) We previously reported the effects of clofibrate and gemfibrozil (one of the fibric acid derivatives) on the synthesis of isoprenoid lipids such as ubiquinone, dolichol and cholesterol in the whole body and cultured cells of rats. 13,15,25) Almost all of the hormone-producing cells secrete either steroid hormone or protein hormone, but trophoblast cells secrete both. We previously reported that clofibric acid and gemfibrozil up-regulate progesterone (steroid hormone) secretions in human extravillous trophoblast cells using an immortalized trophoblast cell-line (TCL-1). 26,27) That is, clofibric acid and gemfibrozil activated steroid hormone synthesis although these substances are inhibitors of HMG-CoA reductase. Steroid hormone is synthesized from cholesterol. Peroxisomes take part in cholesterol synthesis.28) Sterol carrier protein 2 may participate in steroid hormone synthesis, [29][30][31] and is reported to be primarily localized in peroxisomes. [32][33][34] We detected catalase and fatty acyl-CoA oxidase activity in the homogenate of TCL-1 cells, 27) but whether peroxisomes are present in the cells has not been clarified. Therefore, using morphological and biochemical (cell fractionation) techniques, we studied the presence of peroxisomes in these extravillous trophoblast cells.Clofibrate is not only a hypolipidemic agent, but also a peroxisome proliferator-activated receptor a (PPARa) agonist in rodents. With respect to the effect of PPARa agonist on peroxisomal enzymes and proliferation, there are many reports about rat liver. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In human liver cells, some reports demonstrated an increase in peroxisomal enzyme activity caused by PPARa agonist, 5,6,10,12,19) while others reported that there was no effect. 2,3,8,9,14) In all organs except the liver, the effects of PPAR agonist on peroxisomes are little reported in rats, 17...

Pregnancy induced hypertension (PIH) causes hypertensive cerebropathy, deep vein thrombosis, pulmonary embolismlung edema, intrauterine growth retardation, and premature delivery. It is therefore considered to be a serious disease that affects both mother and fetus. However, the mechanism through which PIH induces its clinical symptoms is unknown. At first, damage to vascular endothelial cells induces vasoconstriction and hemoconcentration, resulting in fetoplacental circulation dysfunction. Then, clinical symptoms such as hypertension and protein urea are induced.As described above, the damage caused to vascular endothelial cells is the main pathogenic factor in PIH and results in decreased concentrations of vasodilatatory factors. Therefore, it is assumed that circulation homeostasis is disrupted. The prostaglandin I 2 (PGI 2 )-thromboxane A 2 (TXA 2 ) adjustment system is present in many circulation control systems. Prostaglandin I 2 is synthesized in the endovascular system and acts as a vasodilator in addition to its inhibitory effect on platelet aggregation. In contrast, TXA 2 is synthesized by platelets, acts as a vasoconstrictor, and induces platelet aggregation. Furthermore, PGI 2 and TXA 2 are synthesized from the same precursor, arachidonic acid. These prostaglandins, which have opposite effects, are synthesized in close proximity to each other, such as in blood vessels and platelets, and maintain circulation homeostasis. Therefore, the PGI 2 -TXA 2 balance is considered to be a complex mechanism for circulation control. Additionally, PGI 2 and TXA 2 are synthesized in the placenta, umbilical vein, uterine blood vessel, amnion, chorionic villi, and decidua. The PGI 2 -TXA 2 balance is considered to be very important in the fetoplacental circulating system; therefore, an imbalance in this system may play an important part in PIH pathogenesis.1) In another report, production of PGI 2 was decreased and TXA 2 was increased in the blood, urine, and tissues of PIH maternal and fetal tissues, indicating that the PGI 2 -TXA 2 equilibrium in these tissues is pushed towards TXA 2 . Similar results have also been reported in umbilical and placental tissue.2) These differences may depend on (1) the activity of prostaglandin production enzymes, (2) the content of these enzymes, and (3) the activity of inhibitors for these enzymes.Satoh et al. reported that the activity of enzymes such as cyclooxygenase-2 (COX-2), which takes part in the synthesis of PGI 2 , is decreased in the endothelium of the umbilical vein in patients with severe PIH, resulting in an imbalance in the PGI 2 -TXA 2 system that leads to TXA 2 predominance. 3)However, in their report, no distinction between COX-1 and COX-2 was made because the isozymes of COX had not yet been discovered. In addition, Keirse et al. determined the contents of COX and PGI 2 synthetase using an immunoradiometric assay with monoclonal antibody. 4,5) In their report, COX was induced and increased with increasing gestational age, but there was no difference in the level ...