Characterization of in vitro and in vivo bioactivity of a ferulic acid-2-Hydroxypropyl-ß-cyclodextrin inclusion complex.

Ferulic acid (FA) belongs to the family of phenolic acids and exhibits a wide variety of biological activities. However, the bioavailability of FA is not optimal, owing to its limited aqueous solubility. Several methods have been developed to increase FA bioavailability and enhance its cytoprotective effects. Complexing FA with cyclodextrins (CDs) may provide an alternative method to approach these goals. In this study, we prepared an FA-2-hydroxypropyl-ß-CD (FA-HP-ß-CD) complex, at a 1:1 M ratio of FA to HP-ß-CD, which was characterized by 1H NMR, two-dimensional rotating frame spectroscopy and differential scanning calorimetry. Aqueous solubility of FA was improved after complexing with HP-ß-CD. Furthermore, in vitro and in vivo experimental results indicated that the FA-HP-ß-CD complex had greater bioactivity than FA alone. Therefore, we can conclude that the limitations of FA usage due to low aqueous solubility and bioavailability can be overcome by creating an HP-ß-CD inclusion complex with the hydrophobic FA.

ß-Sitosterol-2-hydroxypropyl-ß-cyclodextrin inclusion complex: Characterization and inhibitory effect on adipogenesis in 3T3-L1 pre-adipocytes.

ß-Sitosterol (Sit) has been used as a functional food additive. Among its many beneficial effects, this phytosterol plays a role in controlling obesity by inhibiting the adipogenesis process of pre-adipocytes. However, the highly lipophilic character of Sit limits its bioavailability. In the present study, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used to form a complex with Sit, namely the Sit-HP-ß-CD inclusion complex, and the inhibitory effect of this complex on adipogenesis in the 3T3-L1 pre-adipocyte cell line was investigated. The results of DSC, TLC, 1H NMR spectroscopy, and 2D ROESY showed that the Sit-HP-ß-CD inclusion complex was successfully synthesized. In addition, the inhibitory effect of the Sit-HP-ß-CD inclusion complex on adipogenesis was evaluated using the Oil Red O staining method and western blot analysis after a 14-day adipogenesis induction in 3T3-L1 pre-adipocytes. The results showed that the Sit-HP-ß-CD inclusion complex had a higher efficiency than Sit in reducing intracellular lipid accumulation and the expression levels of PPARγ and FAS in 3T3-L1 cells, suggesting that the inhibitory effect on adipogenesis was improved by the formation of the Sit and HP-ß-CD complex.

A water-based topical Chinese traditional medicine (Zicao) for wound healing developed using 2-hydroxypropyl-ß-cyclodextrin.

Zicao is a traditional Chinese herbal medicine that has been used for the topical treatment of wounds in the form of oil-based ointment for several hundred years. To overcome the disadvantages of oil-based ointment such as irritation, discomfort, and difficulty in cleaning, this study developed a water-based topical formulation of Zicao. An ethanol extract of Zicao was included in 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) to form a water-soluble Zicao-HP-ß-CD complex. The formation of the Zicao-HP-ß-CD complex was determined using LC-MS, 1H NMR, ROSEY, and solubility analysis. The bioactivity of Zicao-HP-ß-CD complex in aqueous solution was evaluated using cellular uptake in vitro and experimental excision wounds in vivo. The LC-MS, 1H NMR, ROESY, and solubility analyses results show that Zicao extract was successfully included by the HP-ß-CD. The results of the cellular uptake in vitro and wound healing in vivo suggest that the effect of Zicao was enhanced following the formation of the Zicao-HP-ß-CD complex. Therefore, we concluded that complexation with HP-ß-CD might provide a potential method for developing an effective water-based topical solution of Zicao.

Enhancement of rhubarb extract solubility and bioactivity by 2-hydroxypropyl-ß-cyclodextrin.

Rhubarb is a traditional Chinese medicinal herb, and the ethanolic extract of rhubarb consists of active anthraquinones, which are hydrophobic and have antiproliferative effects on hepatoma cell lines. To increase the aqueous solubility of rhubarb and study the consequent bioavailability, the ethanolic extract of rhubarb was complexed with 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), a cyclic oligosaccharide that has a hydrophilic outer surface and a hydrophobic central cavity, to form a rhubarb-HP-ß-CD complex. This complex was characterized by performing nuclear magnetic resonance spectroscopy, two-dimensional rotating frame spectroscopy and thin layer chromatography to confirm the inclusion of anthraquinones from rhubarb extract in HP-ß-CD (weight ratio of rhubarb extract:HP-ß-CD=1:9). We investigated the effects of complexing rhubarb extract with HP-ß-CD on the growth of Huh7 and HepG2 cells by performing cytotoxicity analysis, cellular uptake test, and colony formation assay. Our results showed that complexation of rhubarb extract with HP-ß-CD increased the aqueous solubility and bioavailability of rhubarb and thus enhanced its effect on hepatoma cells.