胃肠道吸收和调节棘叶的黄胺
Junwei Chow1, Xiaolei Yang1, Jiarong Hu1
1School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai, 201203, P.R. China.
棘叶叶黄酸 (HLF) 由于胃肠道吸收有限,表现为口服生物利用性较差. 它们的吸收受剂量,pH值和位置的影响,涉及被动扩散,活跃运输和新陈代谢.
科学领域:
- 药理学和药理动力学 药理学和药理动力学
- 自然产品化学 自然产品化学
- 胃肠道生理学 胃肠道生理学
背景情况:
- 叶叶黄酸 (HLF) 常用于心血管和脑血管疾病.
- 胃肠道吸收行为和HLF组件的机制在很大程度上仍未被阐明.
研究的目的:
- 为了研究关键HLF成分的胃肠道吸收和调节机制:4'-O-glucosylvitexin (GLV),2'-O-rhamnosylvitexin (RHV),vitexin (VIT),rutin (RUT) 和hyperoside (HP).
主要方法:
- 用于体外 (Caco-2细胞),现场 (老鼠胃和小肠) 和体内模型来评估黄类吸收.
- 量化明显透系数 (Papp),每小时的吸收百分比 (A) 和吸收率 (公式:见文本).
- 评估了剂量,pH值,吸收增强剂和载体调节剂对黄类吸收的影响.
主要成果:
- 五种黄类药物在Caco-2细胞中表现出明显的低透性,这表明吸收不良.
- GLV,RHV,VIT和RUT在老鼠的胃和小肠中显示出有限的吸收.
- 过氧化物 (HP) 在老鼠小肠中显示出相对更好的吸收.
- 吸收是剂量依赖的,pH依赖的,区域选择性的,涉及被动扩散和活性传输.
- 黄类药物经历了肠道分泌,胆汁分泌和肠道微生物群代谢,GLV和RHV表现出肠肝循环.
- 胆汁盐,二甲基硫酸盐和传送调节剂 (如维拉帕米尔化) 增强了吸收.
结论:
- 高低频组件通过被动扩散和主动传输机制的组合被吸收.
- 肠道微生物群的新陈代谢,胆汁分泌和肠道排泄显著影响HLF的吸收.
- 这些黄酸被归类为生物制药分类系统 (BCS) III类,其特点是具有高溶解度和低透性,导致口服生物可用性差.
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