title: Comparative pharmacokinetics of arctigenin in normal and type 2 diabetic rats after oral and intravenous administration.
abstract: Arctigenin is the main active ingredient of Fructus Arctii for the treatment of type 2 diabetes. In this study, the pharmacokinetics of arctigenin in normal and type 2 diabetic rats following oral and intravenous administration was investigated. As compared to normal rats, Cmax and AUC(0-10h) values of oral arctigenin in diabetic rats increased by 356.8% and 223.4%, respectively. In contrast, after intravenous injection, the Cmax and AUC(0-10h) values of arctigenin showed no significant difference between diabetic and normal rats. In order to explore how the bioavailability of oral arctigenin increased under diabetic condition, the absorption behavior of arctigenin was evaluated by in situ single-pass intestinal perfusion (SPIP). The results indicated that arctigenin was a substrate of P-glycoprotein (P-gp). The absorption difference of arctigenin in the normal and diabetic rats could be eliminated by the pretreatment of classic P-gp inhibitor verapamil, suggesting that P-gp might be the key factor causing the absorption enhancement of arctigenin in diabetic rats. Further studies revealed that the uptake of rhodamine 123 (Rho123) in diabetic rats was significantly higher, indicating that diabetes mellitus might impair P-gp function. Consistently, a lower mRNA level of P-gp in the intestine of diabetic rats was found. In conclusion, the absorption of arctigenin after oral administration was promoted in diabetic rats, which might be partially attribute to the decreased expression and impaired function of P-gp in intestines.
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Zeng
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Dong
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Nan-nan
authors.initials: NN
authors.lastname: He
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Chun-jie
authors.initials: CJ
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Chinese Materia Medica Analysis, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: yfxiacpu@126.com.
authors.forename: Yu-feng
authors.initials: YF
authors.lastname: Xia
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005663:Furans / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D017705:Lignans / Q000493:pharmacokinetics*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005663:Furans; D017705:Lignans; C071942:arctigenin
keywords: Absorption; Arctigenin; Arctigenin (PubChem CID: 64981); Diabetes mellitus; In situ single-pass intestinal perfusion; Isobergapten (PubChem CID: 68082); Ko143 hydrate (PubChem CID: 71311836); P-glycoprotein; Pharmacokinetics; Probenecid (PubChem CID: 4911); Rhodamine123 (PubChem CID: 9929799); Streptozotocin (PubChem CID: 29327); Verapamil hydrochloride (PubChem CID: 62969)