title: Effect of chito-oligosaccharide on the intestinal absorptions of phenylethanoid glycosides in Fructus Forsythiae extract.
abstract: Phenylethanoid glycosides, the main active ingredients in Fructus Forsythiae extract possesses strong antibacterial, antioxidant and antiviral effects, and their contents were higher largely than that of other ingredients such as lignans and flavones, but their absolute bioavailability orally was significantly low, which influenced clinical efficacies of its oral preparations seriously. In the present study, the absorption mechanism of phenylethanoid glycosides was studied using in vitro Caco-2 cell model. And the effect of chito-oligosaccharide (COS) on the intestinal absorption of phenylethanoid glycosides in Fructus Forsythiae extract was investigated using in vitro, in situ and in vivo models. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenylethanoid glycosides in Fructus Forsythiae extract so with that in monomers was mainly restricted by the tight junctions, and influenced by efflux transporters (P-gp and MRP2). Meanwhile, the absorption of phenylethanoid glycosides in Fructus Forsythiae extract could be improved by COS. Besides, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenylethanoid glycosides compared to the control group (p<0.05), and was all safe for the Caco-2 cells. The observations from single-pass intestinal perfusion in situ model showed that the intestinal absorption of phenylethanoid glycosides can be enhanced by COS. Meanwhile, the absorption enhancing effect of phenylethanoid glycosides might be saturable in different intestine sites. In pharmacokinetics study, COS at dosage of 25mg/kg improved the bioavailability of phenylethanoid glycosides in Fructus Forsythiae extract to the greatest extent, and was safe for gastrointestine from morphological observation. In addition, treatment with Fructus Forsythiae extract with COS at dosage of 25mg/kg prevented MDCK cell damage upon influenza virus propagation better than that of control. All findings above suggested that COS at dosage of 25mg/kg might be safe and effective absorption enhancer for improving the bioavailability of phenylethanoid glycosides and the antiviral activity in vitro in Fructus Forsythiae extract.
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Meteria Medica, Jiangsu Provinical Academy of Chinese Medicine, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Tan
authors.affiliation: Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Paediatrics, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shan
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, PR China.
authors.forename: Baochang
authors.initials: B
authors.lastname: Cai
authors.affiliation: College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, PR China; Jiangsu Engineering Research Center for Efficient Delivery System of TCM, PR China; Nanjing Engineering Research Center for Industrialization of Chinese Medicine Pellets, PR China. Electronic address: diliuqing@hotmail.com.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Di
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D018938:Caco-2 Cells; D002109:Caffeic Acids; D004285:Dogs; D031657:Forsythia / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry; D005960:Glucosides; D006027:Glycosides / Q000493:pharmacokinetics*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D007408:Intestinal Absorption; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D015394:Molecular Structure; D009844:Oligosaccharides / Q000494:pharmacology*; D010936:Plant Extracts / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley
chemical_list: D000998:Antiviral Agents; D002109:Caffeic Acids; D005960:Glucosides; D006027:Glycosides; D009844:Oligosaccharides; D010936:Plant Extracts; C552409:forsythoside B; C058049:forsythiaside
keywords: Absorption mechanism; Antiviral activity; Chito-oligosaccharide; Fructus Forsythiae extract; Phenylethanoid glycosides; Tight junction