Pharmacokinetic profiles of the five isoflavonoids from Pueraria lobata roots in the CSF and plasma of rats

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• 作者：Bing-Xin Xiao^a ; ^b ; Li Feng^a ; Fang-Rui Cao^a ; Rui-Le Pan^a ; Yong-Hong Liao^a ; Xin-Min Liu^a ; Qi Chang^a ; ^{qchang@implad.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CSF ; cerebrospinal fluid ; PIF ; Pueraria isoflavonoids ; PU ; puerarin ; MPU ; 3&prime ; -methoxypuerarin ; HPU ; 3&prime ; -hydroxypuerarin ; DA ; daidzein ; DAC ; daidzein-8-c-Apiosyl-(1-6)-glycoside ; ICA ; Icarisid II
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：26 May 2016
• 年：2016
• 卷：184
• 期：Complete
• 页码：22-29
• 全文大小：1279 K

文摘

Traditional Chinese medicine Radix Puerariae, the roots of Pueraria lobata (Wild.) Ohwi., has been widely used for the treatment of cardiovascular and cerebrovascular diseases in China for centuries. Isoflavonoids are believed the active components of this herb.

Aim of this study

The present study aims to investigate the brain penetration and pharmacokinetics of five active isoflavonoids in the ventricular CSF and plasma of rats after intravenous administration of a Pueraria isoflavonoids (PIF) extract, to better understand the active components of this herb for neuro-activities.

Material and methods

Under anesthesia condition, SD rats (n=6) were successively suffered two surgeries for implanting cannulas at lateral ventricle and right jugular vein for brain microdialysis and blood collection, respectively. After recovery, the rats received intravenous dose of PIF at 80 mg/kg and the concentrations of puerarin (PU), 3′-methoxypuerarin (MPU), 3′-hydroxypuerarin (HPU), daidzein (DA) and daidzein-8-C-apiosyl-(1-6)-glycoside (DAC) in the ventricular dialysate and plasma samples were determined using a ultra-fast liquid chromatography tandem mass spectrometry method.

Results

Complete concentration versus time profiles of the five components in plasma and four components except for HPU in ventricular CSF were obtained. After dosing, the average C₀ values of PU, MPU, DA, DAC and HPU in plasma were estimated 6.53, 13.72, 1.54, 15.84 and 86.07 µg/mL, and PU, MPU, DA and DAC were rapidly penetrated to the brain and reached to their C_max of 521.52, 415.00, 74.34 and 380.03 ng/mL in CSF at about 0.5–0.8 h, respectively. The elimination t_1/2 of PU, DA and DAC in CSF and plasma were no significant difference, while the t_1/2 of MPU in ventricular CSF was longer than that in plasma which may attributable to the different physiological environment of central and peripheral compartments. The brain penetration index (AUC_CSF/AUC_plasma) was found to be about 9.29, 7.25, 11.96, and 4.21% for PU, MPU, DA, and DAC respectively.

Conclusion

PU, MPU, DA, DAC can quickly penetrate to the brain through the blood brain barrier (BBB) and might be responsible for the neuro-pharmacological activities of P. lobata.