Pharmacokinetic and bioavailability study of kurarinone in dog plasma by UHPLC–MS/MS

Abstract

Kurarinone, a natural prenylated flavonone isolated from Sophora flavescens, has been exhibited various activities. This study aimed to establish a simple and sensitive ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for determining kurarinone in dog plasma. Acetonitrile-mediated precipitation was applied for sample pretreatment. Chromatographic separation was achieved on a Waters ACQUITY HSS T3 (100 × 2.1 mm, i. d., 1.8 μm) column with gradient elution using water containing 0.1% formic acid and acetonitrile as mobile phase. Quantitation was performed using an electrospray ionization source in negative multiple reaction monitoring mode. The linearity of this method was over the concentration range 0.1-500 ng/mL with the lowest limit of quantification (LLOQ) of 0.1 ng/mL. The intra-and inter-day precision was less than 10.51% and the accuracy ranged from 94.85% to 97.72%, respectively. The extraction recovery of kurarinone in dog plasma was more than 82.37% and no significant matrix effect was observed. The analyte was stable under tested storage conditions. The validated method was further successfully applied to a preclinical pharmacokinetic study of kurarinone in dog after a single intravenous (2 mg/kg) and oral (20 mg/kg) administration. The results revealed that kurarinone was rapidly absorbed into plasma with good bioavailability (38.19%) and low clearance.

In Vitro and In Silico Characterization of Kurarinone as a Dopamine D1A Receptor Antagonist and D2L and D4 Receptor Agonist

“…ADMET assessment by PreADMET predicted kurarinone to be a drug-like molecule capable of crossing the BBB (>4) (Table ). Corroborating with the in silico prediction, previous in vivo studies have demonstrated high absorption and clearance and moderate bioavailability of kurarinone. , Despite a favorable ADME profile, Jiang et al and Yu et al in independent studies have detected kurarinone as a hepatotoxic compound in the S. flavescens extract owing to the hepatic accumulation of the compound and inhibition of fatty acid β-oxidation, resulting in lipid accumulation in the liver.…”

“…Corroborating with the in silico prediction, previous in vivo studies have demonstrated high absorption and clearance and moderate bioavailability of kurarinone. 57 , 58 Despite a favorable ADME profile, Jiang et al 59 and Yu et al 60 in independent studies have detected kurarinone as a hepatotoxic compound in the S. flavescens extract owing to the hepatic accumulation of the compound and inhibition of fatty acid β-oxidation, resulting in lipid accumulation in the liver. In contrast, another study by Nishikawa and colleagues found the induction of heme oxygenase-1 by kurarinone via activation of the KEAP1/Nrf2 pathway and Nrf2 activation plays a protective role against hepatotoxicity.…”

The dual face of microglia (M1/M2) as a potential target in the protective effect of nutraceuticals against neurodegenerative diseases

“…Kurarinone is a naturally occurring prenylated flavanone isolated from Sophora flavescens ( Huang et al, 2020 ). Kurarinone demonstrated promising therapeutic results in a PD mice model.…”

Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone

“…A similar study was performed by Yang et al (2016) , which administered a higher amount of kurarinone (25 and 500 mg/kg by weight) and the stability in rat plasma was monitored for 12 h ( Yang et al, 2016 ). In a similar but different study, Huang et al (2020) developed a UPLC-MS/MS based method to detect the kurarinone levels in dog plasma. In this study, kurarinone was administered at 2 and 20 mg/kg body weight, and the blood plasma level was monitored for 25 h ( Huang et al, 2020 ).…”

“…In a similar but different study, Huang et al (2020) developed a UPLC-MS/MS based method to detect the kurarinone levels in dog plasma. In this study, kurarinone was administered at 2 and 20 mg/kg body weight, and the blood plasma level was monitored for 25 h ( Huang et al, 2020 ).…”