HanLiang Guan1, Dawei Qian2, Hao Ren1, Wei Zhang1, Hui Nie1, Erxing Shang1, Jinao Duan3. 1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. 2. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: qiandwnj@126.com. 3. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: dja@njutcm.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. MATERIALS AND METHODS: A selective and sensitive UPLC-MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF-WEF, FF-TLF, TLF-WEF and FF-TLF-WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student׳s t-test with P<0.05 as the level of significance. RESULTS: FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF-WEF, FF-TLF and FF-TLF-WEF had varying degrees of reduction in comparison with group FF, especially in group FF-TLF-WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF-TLF-WEF were significantly increased compared with those in group FF. CONCLUSIONS: These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones.
ETHNOPHARMACOLOGICAL RELEVANCE: Extracts from Ginkgo biloba L. leaves confer their therapeutic effects through the synergistic actions of flavonoid and terpenoid components, but some non-flavonoid and non-terpenoid components also exist in this extract. In the study of this paper, an investigation was carried out to compare the pharmacokinetic parameters of fourteen compounds to clarify the influences of non-flavonoid and non-terpenoid fraction (WEF) on the pharmacokinetics profile of the flavonoid fraction (FF) and the terpene lactone fraction (TLF) from Ginkgo biloba extracts. MATERIALS AND METHODS: A selective and sensitive UPLC-MS/MS method was established to determine the plasma concentrations of the fourteen compounds to compare the pharmacokinetic parameters after orally administration of FF, TLF, FF-WEF, FF-TLF, TLF-WEF and FF-TLF-WEF with approximately the same dose. At different time points, the concentration of rutin (1), isoquercitrin (2), quercetin 3-O-[4-O-(-β-D-glucosyl)-α-L-rhamnoside] (3), ginkgolide C (4), bilobalide (5), quercitrin (6), ginkgolide B (7), ginkgolide A (8), luteolin (9), quercetin (10), apigenin (11), kaempferol (12), isorhamnetin (13), genkwanin (14) in rat plasma were determined and main pharmacokinetic parameters including T1/2, Tmax, Cmax and AUC were calculated using the DAS 3.2 software package. The statistical analysis was performed using the Student׳s t-test with P<0.05 as the level of significance. RESULTS: FF and WEF had no effect on the pharmacokinetic behaviors and parameters of the four terpene lactones, but the pharmacokinetic profiles and parameters of flavonoids changed while co-administered with non-flavonoid components. It was found that Cmax and AUC of six flavonoid aglycones in group FF-WEF, FF-TLF and FF-TLF-WEF had varying degrees of reduction in comparison with group FF, especially in group FF-TLF-WEF. On the contrary, the values of Cmax, Tmax and AUC of four flavonoid glycosides in group FF-TLF-WEF were significantly increased compared with those in group FF. CONCLUSIONS: These results indicate that non-flavonoid components in Ginkgo biloba extracts could increase the absorption and improve the bioavailability of flavonoid glycosides but decrease the absorption and reduce the bioavailability of flavonoid aglycones.
Authors: Carlos Enrique Escárcega-González; Irma Guadalupe Reynoso-Andeola; Fernando Jaramillo-Juárez; Haydée Martínez-Ruvalcaba; Francisco A Posadas Del Rio Journal: Biochem Res Int Date: 2016-03-03