title: Pharmacokinetic studies of active triterpenoid saponins and the total secondary saponin from Anemone raddeana Regel.
abstract: The rhizome of Anemone raddeana Regel, a Traditional Chinese Medicine (TCM) which has a robust history treating rheumatism and neuralgia. The total secondary saponin (TSS) from it has demonstrated antitumor activity. In this study, a rapid and validated LC-MS/MS method was developed to simultaneously determine the active compounds (Hederacolchiside A1 and Eleutheroside K). Analytes were separated on a reverse-phase C18 column with acetonitrile-water (5mmol/L ammonium acetate) as the mobile phase. This assay showed acceptable linearity (r>0.99) over the concentration range 5-1000 nmol/L for two analytes. The intra- and inter-day precision was within 8.06% and accuracy was ranged from -3.16% to 3.34% for two analytes. The mean extraction recoveries of analytes and IS from rat plasma were all more than 76.0%. Under the developed analytical conditions, the obtained values of main pharmacokinetic parameters (Cmaxand AUC0-t) indicated that the pure compounds were more efficient than the TSS extract in Hederacolchiside A1 and Eleutheroside K absorption. In addition, pharmacokinetic studies of two individual compounds demonstrated their poor oral absorption in rat (aF%, 0.019-1.521). In the study of absorption and transportation of Hederacolchiside A1 and Eleutheroside K in Caco-2 cell monolayer model, the uptake permeability was in 10-6cm/sec range suggesting poor absorption, which confirmed the previous pharmacokinetic profiles in vivo. Interestingly, the uptake ratio of them declined significantly when treated with phloridzin (SGLT1 inhibitor). It indicated that the absorption of Hederacolchiside A1 in intestine was mainly through positive transport and SGLT1 might participate in its active absorption.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Tianli
authors.initials: T
authors.lastname: Lei
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Chongning
authors.initials: C
authors.lastname: Lv
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: xhy411@163.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: jincailu@126.com.
authors.forename: Jincai
authors.initials: J
authors.lastname: Lu
mesh_terms: D000284:Administration, Oral; D031883:Anemone / Q000737:chemistry*; D000818:Animals; D018938:Caco-2 Cells; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012503:Saponins / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014315:Triterpenes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes
keywords: Anemone raddeana regel; Caco-2 cell monolayer model; LC–MS/MS; Pharmacokinetics; Triterpenoid saponins