Luo Jie, Wen Wen, Chen Jie, Zeng Xiaobo, Wang Ping, Xu Shijun
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Pharmacol. 2023 Apr 6;14:1109279. doi: 10.3389/fphar.2023.1109279. eCollection 2023.
This researcher focused at the evodiamine and dehydroevodiamine tissue distribution and structure-pharmacokinetics (PK) relationship after intravenous injection in mice. Using a transmembrane transport experiment, the permeability of evodiamine and dehydroevodiamine on Caco-2 cells was evaluated. The tissue distribution and pharmacokinetics (PK) of evodiamine and dehydroevodiamine in mice were studied. To comprehend the connection between structure and tissue distribution, physicochemical property evaluations and molecular electrostatic potential (MEP) calculations were performed. Dehydroevodiamine's Papp values in vitro were 10 cm/s, whereas evodiamine's were 10 cm/s. At a dose of 5 mg/kg, the brain concentration of dehydroevodiamine was 6.44 times more than that of evodiamine. By MEP or physicochemical measures, the permeability difference between evodiamine and dehydroevodiamine is unaffected. The dihedral angle of the stereo-structure appears to be the main cause of the difference in tissue distribution ability between evodiamine and dehydroevodiamine. Dehydroevodiamine has a dihedral angle of 3.71° compared to 82.34° for evodiamine. Dehydroevodiamine can more easily pass through the phospholipid bilayer than evodiamine because it has a more planar stereo-structure. Dehydroevodiamine is therefore more likely to pass cross the blood-brain barrier and enter the brain in a tissue-specific manner.
该研究人员聚焦于吴茱萸碱和去氢吴茱萸碱在小鼠静脉注射后的组织分布及构效-药代动力学（PK）关系。通过跨膜转运实验，评估了吴茱萸碱和去氢吴茱萸碱在Caco-2细胞上的通透性。研究了吴茱萸碱和去氢吴茱萸碱在小鼠体内的组织分布和药代动力学（PK）。为了理解结构与组织分布之间的联系，进行了物理化学性质评估和分子静电势（MEP）计算。去氢吴茱萸碱的体外表观渗透系数（Papp）值为10 cm/s，而吴茱萸碱的为10 cm/s。在5 mg/kg的剂量下，去氢吴茱萸碱的脑浓度是吴茱萸碱的6.44倍。通过MEP或物理化学方法，吴茱萸碱和去氢吴茱萸碱之间的通透性差异不受影响。立体结构的二面角似乎是吴茱萸碱和去氢吴茱萸碱组织分布能力差异的主要原因。去氢吴茱萸碱的二面角为3.71°，而吴茱萸碱为82.34°。去氢吴茱萸碱比吴茱萸碱更容易穿过磷脂双分子层，因为它具有更平面的立体结构。因此，去氢吴茱萸碱更有可能以组织特异性方式穿过血脑屏障并进入大脑。
