Inhibitory Effect of Sinomenine on Human Glioblastoma and Its Pharmacokinetic Characteristics
10.13422/j.cnki.syfjx.20241442
- VernacularTitle:青藤碱对人脑胶质瘤的抑制作用及肿瘤内药代动力学特征
- Author:
Yue JIAO
1
;
Yumao JIANG
2
;
Danqiao WANG
1
;
Jingyi WANG
1
;
Yang LIU
1
;
Xiaoliang ZHAO
1
;
Zhiguo WANG
1
;
Tao LI
1
Author Information
1. Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases，Experimental Research Center， China Academy of Chinese Medical Sciences，Beijing 100700， China
2. Scientific Research Center， Gannan Medical University， Ganzhou 341000， China
- Publication Type:Journal Article
- Keywords:
sinomenine;
human glioblastoma;
blood-tumor barrier;
pharmacokinetics
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(23):179-186
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg-1） and model groups （50， 100， 150 mg·kg-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the Cmax and AUC in the tumor significantly increased， Tmax shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.
