title: Relevance of the Pharmacokinetic and Pharmacodynamic Profiles of Puerariae lobatae Radix to Aggregation of Multi-Component Molecules in Aqueous Decoctions.
abstract: The complexity of traditional Chinese medicines (TCMs) is related to their multi-component system. TCM aqueous decoction is a common clinical oral formulation. Between molecules in solution, there exist intermolecular strong interactions to form chemical bonds or weak non-bonding interactions such as hydrogen bonds and Van der Waals forces, which hold molecules together to form "molecular aggregates". Taking the TCM Puerariae lobatae Radix (Gegen) as an example, we explored four Gegen decoctions of different concentration of 0.019, 0.038, 0.075, and 0.30 g/mL, named G-1, G-2, G-3, and G-4. In order of molecular aggregate size (diameter) the four kinds of solution were ranked G-1 < G-2 < G-3 < G-4 by Flow Cell 200S IPAC image analysis. A rabbit vertebrobasilar artery insufficiency (VBI) model was set up and they were given Gegen decoction (GGD) at a clinical dosage of 0.82 g/kg (achieved by adjusting the gastric perfusion volume depending on the concentration). The HPLC fingerprint of rabbit plasma showed that the chemical component absorption into blood in order of peak area values was G-1 < G-2 > G-3 > G-4. Puerarin and daidzin are the major constituents of Gegen, and the pharmacokinetics of G-1 and G-2 puerarin conformed with the two compartment open model, while for G-3 and G-4, they conformed to a one compartment open model. For all four GGDs the pharmacokinetics of daidzin complied with a one compartment open model. FQ-PCR assays of rabbits' vertebrobasilar arterial tissue were performed to determine the pharmacodynamic profiles of the four GGDs. GGD markedly lowered the level of AT₁R mRNA, while the AT₂R mRNA level was increased significantly vs. the VBI model, and G-2 was the most effective. In theory the dosage was equal to the blood drug concentration and should be consistent; however, the formation of molecular aggregates affects drug absorption and metabolism, and therefore influences drugs' effects. Our data provided references for the rational use of Chinese medicines in the clinic, such as the best oral preparation and decoction concentration.
authors.affiliation: The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou 350003, China. hzf_ketizu@163.com.|The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. hzf_ketizu@163.com.
authors.forename: Bili
authors.initials: B
authors.lastname: Su
authors.affiliation: The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou 350003, China. cld_ketizu@163.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Kan
authors.affiliation: The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. 13860662716@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Xie
authors.affiliation: The Institute of Drug Research, Fujian Academy of Traditional Chinese Medicine, Fuzhou 350003, China. huj@fjtcm.edu.cn.|The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. huj@fjtcm.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Hu
authors.affiliation: The College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China. pws@fjtcm.edu.cn.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Pang
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D005260:Female; D015870:Gene Expression; D007529:Isoflavones / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008516:Medicine, Chinese Traditional; D029908:Pueraria / Q000737:chemistry*; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012996:Solutions; D017585:Ultrasonography, Doppler, Transcranial; D014715:Vertebrobasilar Insufficiency / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology
chemical_list: D004365:Drugs, Chinese Herbal; D007529:Isoflavones; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012996:Solutions; C013908:daidzin; C033607:puerarin
keywords: Puerariae lobatae Radix decoction; molecular aggregation; pharmacodynamic profiles; pharmacokinetic profiles