title: Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.
abstract: Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level.
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Kexia
authors.initials: K
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Gu
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Gaosheng
authors.initials: G
authors.lastname: Hu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: cxh_syphu@hotmail.com.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address: jiajingming@163.com.
authors.forename: Jingming
authors.initials: J
authors.lastname: Jia
mesh_terms: D000818:Animals; D001682:Biological Availability; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D010743:Phospholipids / Q000737:chemistry*; D011794:Quercetin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D010743:Phospholipids; D011794:Quercetin; D002251:Carbon Tetrachloride
keywords: Bioavailability; Hepatoprotective effect; Quercetin; Quercetin-phospholipid complex