title: The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.
abstract: Paeoniflorin and sinomenine, derived from the root of Paeonia lactiflora Pall. (family Ranunculaceae) and the stem of Sinomenium acutum Rehder & Wilson (family Menispermaceae), respectively, have been, and are currently, widely used for treatment of rheumatic and arthritic diseases in China and Japan. Our previous studies demonstrated that sinomenine could significantly improve the bioavailability of paeoniflorin in rats, but the underlying mechanisms remain unknown. The present study aims to investigate the intestinal kinetic absorptive characteristics of paeoniflorin as well as the absorptive behavior influenced by co-administration of sinomenine using an in vitro everted rat gut sac model. The results showed a good linear correlation between the paeoniflorin absorption in sac contents and the incubation time from 0 to 90 min. However, the concentration dependence showed that a non-linear correlation exists between the paeoniflorin absorption and its concentrations from 10 to 160 microM, and the absorption was saturated at about 80 microM of the drug. Sinomenine at 16 and 136 microM concentrations could significantly enhance the absorption of paeoniflorin (20 microM) by 1.5- and 2.5-fold, respectively. Moreover, two well-known P-glycoprotein inhibitors, verapamil and quinidine, could significantly elevate the absorption of paeoniflorin by 2.1- and 1.5-fold, respectively. Furthermore, sinomenine in a pattern, which influenced paeoniflorin's absorption, manifested as similar to that of P-glycoprotein inhibitors. In conclusion, sinomenine significantly enhance the intestinal absorption of paeoniflorin, subsequently improve the bioavailability of paeoniflorin. The mechanism underlying the improvement of paeoniflorin's bioavailability was proposed that sinomenine could decrease the efflux transport of paeoniflorin by P-glycoprotein.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, PR China.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chan
authors.forename: Zhong Qiu
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Zhi Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yuen Fan
authors.initials: YF
authors.lastname: Wong
authors.forename: Hong-Xi
authors.initials: HX
authors.lastname: Xu
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001565:Benzoates / Q000378:metabolism*; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D004077:Digoxin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005960:Glucosides / Q000378:metabolism*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D039821:Monoterpenes; D009019:Morphinans / Q000494:pharmacology*; D029596:Paeonia; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D032841:Sinomenium; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology; D006027:Glycosides
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000893:Anti-Inflammatory Agents; D001565:Benzoates; D001952:Bridged-Ring Compounds; D004077:Digoxin; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D039821:Monoterpenes; D009019:Morphinans; D011802:Quinidine; D014700:Verapamil; C015423:peoniflorin; D006027:Glycosides; C009271:sinomenine