Pharmacokinetic properties of trifolirhizin, (–)-maackiain, (–)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration ofSophora tonkinensisextract in rats

Abstract

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea. This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed. 6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

Lack of Correlation between In Vitro and In Vivo Studies on the Inhibitory Effects of (‒)-Sophoranone on CYP2C9 Is Attributable to Low Oral Absorption and Extensive Plasma Protein Binding of (‒)-Sophoranone

“…However, little information is yet to be reported on the C max values of SPN after oral administration of SPN. As stated in the Introduction, from our previous study, the C max of SPN was reported to be 13.1 ng/mL in rats after oral dosing of 12.9 mg/kg SPN in rats [8]. Thus, we investigated whether SPN affects the pharmacokinetics of diclofenac and 4 -hydroxydiclofenac, produced by hepatic CYP2C9 enzyme, in rats.…”

Trifolirhizin relieves renal injury in a diabetic nephropathy model by inducing autophagy and inhibiting oxidative stress through the regulation of PI3K/AKT/mTOR pathway

“…Inadequate podocyte autophagy has been observed in patients with diabetes mellitus and proteinuria [7]. Impaired autophagy activity leads to the pathogenesis of DN, and the recovery of autophagy activity may be a promising therapeutic target for DN [8]. In addition, apoptosis and oxidative stress are important biological mechanisms involved in the pathogenesis of DN.…”

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC‐Q‐TOF‐MSE

“…Alkaloids are considered as the major bioactive and toxic components (He et al, 2019;Lu et al, 2014;Wang et al, 2017;You et al, 2020). Recently, more studies have confirmed that flavonoids may be one of the primary pharmacologically active and toxic constituents (Jang et al, 2015;Lee et al, 2015;Pan et al, 2016;Sasajima et al, 1978). Nevertheless, studies on S. tonkinensis often focus on alkaloids and less on other compounds.…”