Abstract
This work aimed at improving the water solubility of Ginsenoside (G)-Re by forming an inclusion complex. The solubility parameters of G-Re in alpha (α), beta (β), and gamma (γ) cyclodextrin (CD) were investigated. The phase solubility profiles were all classified as AL-type that indicated the 1:1 stoichiometric relationship with the stability constants Ks which were 22 M−1 (α-CD), 612 M−1 (β-CD), and 14,410 M−1 (γ-CD), respectively. Molecular docking studies confirmed the results of phase solubility with the binding energy of −4.7 (α-CD), −5.10 (β-CD), and −6.70 (γ-CD) kcal/mol, respectively. The inclusion complex (IC) of G-Re was prepared with γ-CD via the water-stirring method followed by freeze-drying. The successful preparation of IC was confirmed by powder X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). In-vivo absorption studies were carried out by LC-MS/MS. Dissolution rate of G-Re was increased 9.27 times after inclusion, and the peak blood concentration was 2.7-fold higher than that of pure G-Re powder. The relative bioavailability calculated from the ratio of Area under the curve AUC0–∞ of the inclusion to pure G-Re powder was 171%. This study offers the first report that describes G-Re’s inclusion into γ-CD, and explored the inclusion complex’s mechanism at the molecular level. The results indicated that the solubility could be significantly improved as well as the bioavailability, implying γ-CD was a very suitable inclusion host for complex preparation of G-Re.
Highlights
Ginsenoside Re (G-Re), a protopanaxatriol with a tetracyclic triterpene structure, is one of the most abundant ginsenosides in Panax ginseng
Studies reported that G-Re has a variety of pharmacological effects, especially on the cardiovascular system [3,4,5]: G-Re has been proven to play a role in reducing ischemic damage to cardiomyocytes
Linearity is the characteristic of an AL-type system in phase solubility which implied that the water-soluble complexes were formed in solution
Summary
Ginsenoside Re (G-Re), a protopanaxatriol with a tetracyclic triterpene structure, is one of the most abundant ginsenosides in Panax ginseng. Studies reported that G-Re has a variety of pharmacological effects, especially on the cardiovascular system [3,4,5]: G-Re has been proven to play a role in reducing ischemic damage to cardiomyocytes. It maintains calcium transport, protective function, and mitochondrial structure in cardiomyocytes, while enhancing their antioxidant capacity [6]. Pharmacokinetic studies have shown that after oral administration, the tmax of G-Re was short and the bioavailability was low [8,9,10]. Due to the poor solubility and insufficient blood concentration, G-Re is not suitable for drug development [11]; improving the solubility of G-Re and thereby its bioavailability are the key points for the drug development of G-Re
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