Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression
Baicalin, an important flavonoid isolated from Scutellaria baicalensis Georgi, is a Chinese herb widely used in clinical practice. We previously reported the in vivo accumulation of baicalin in rats with intrahepatic cholestasis (IHC) after a single dose. However, the effects of the long-term admini...
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Elsevier
2023-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844022039779 |
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| author | Yue Zu Yanan Liu Lulu Lan Chen Zhu Chengliang Zhang Dong Liu |
| author_facet | Yue Zu Yanan Liu Lulu Lan Chen Zhu Chengliang Zhang Dong Liu |
| author_sort | Yue Zu |
| collection | DOAJ |
| description | Baicalin, an important flavonoid isolated from Scutellaria baicalensis Georgi, is a Chinese herb widely used in clinical practice. We previously reported the in vivo accumulation of baicalin in rats with intrahepatic cholestasis (IHC) after a single dose. However, the effects of the long-term administration of baicalin on its pharmacokinetics are unknown. Thus, we investigated the disposition of baicalin in normal rats and those with IHC after single and multiple consecutive administrations. In addition, we further investigated the effect of baicalin on multidrug resistance protein 2 (MRP2) in vivo to explore the underlying mechanism. In our study, the liquid chromatography-mass spectrometry (LC-MS) method established to determine baicalin concentrations in rat blood was simple, specific, and with linearity (R2 = 0.9980) in the range of 1.01–506.00 μg/mL. The relative standard deviations (RSD) for intra-day and inter-day precision were not more than 10.55%, and the intra-day and inter-day accuracies were 94.94%–109.13%. The recovery rate and stability were in line with the requirements of the quantitative analysis of biological samples as stated in the Chinese Pharmacopoeia (2020 Edition). Compared with that in normal rats, the Cmax and t1/2 increased significantly in EE-induced rats with IHC, whereas the clearance (CL) decreased after a single administration of baicalin. However, the area under the curve decreased, CL increased, and the t1/2 was shortened after the continuous administration of baicalin in the IHC rat model compared with the single administration of baicalin, and the pharmacokinetic characteristics were similar to those in normal rats. Moreover, MRP2 expression increased in rats with IHC with the continuous administration of baicalin. Continuous baicalin intervention could effectively reduce its accumulation in rats with IHC, and the mechanism may be attributed to its enhancement of MRP2 expression. |
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| spelling | doaj.art-f5cf3b797fd4427d8f8a47f8bb8d4e232023-02-03T04:58:36ZengElsevierHeliyon2405-84402023-01-0191e12689Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expressionYue Zu0Yanan Liu1Lulu Lan2Chen Zhu3Chengliang Zhang4Dong Liu5Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaCorresponding author.; Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaCorresponding author.; Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaBaicalin, an important flavonoid isolated from Scutellaria baicalensis Georgi, is a Chinese herb widely used in clinical practice. We previously reported the in vivo accumulation of baicalin in rats with intrahepatic cholestasis (IHC) after a single dose. However, the effects of the long-term administration of baicalin on its pharmacokinetics are unknown. Thus, we investigated the disposition of baicalin in normal rats and those with IHC after single and multiple consecutive administrations. In addition, we further investigated the effect of baicalin on multidrug resistance protein 2 (MRP2) in vivo to explore the underlying mechanism. In our study, the liquid chromatography-mass spectrometry (LC-MS) method established to determine baicalin concentrations in rat blood was simple, specific, and with linearity (R2 = 0.9980) in the range of 1.01–506.00 μg/mL. The relative standard deviations (RSD) for intra-day and inter-day precision were not more than 10.55%, and the intra-day and inter-day accuracies were 94.94%–109.13%. The recovery rate and stability were in line with the requirements of the quantitative analysis of biological samples as stated in the Chinese Pharmacopoeia (2020 Edition). Compared with that in normal rats, the Cmax and t1/2 increased significantly in EE-induced rats with IHC, whereas the clearance (CL) decreased after a single administration of baicalin. However, the area under the curve decreased, CL increased, and the t1/2 was shortened after the continuous administration of baicalin in the IHC rat model compared with the single administration of baicalin, and the pharmacokinetic characteristics were similar to those in normal rats. Moreover, MRP2 expression increased in rats with IHC with the continuous administration of baicalin. Continuous baicalin intervention could effectively reduce its accumulation in rats with IHC, and the mechanism may be attributed to its enhancement of MRP2 expression.http://www.sciencedirect.com/science/article/pii/S2405844022039779Intrahepatic cholestasisBaicalinPharmacokineticsAccumulationMRP2 |
| spellingShingle | Yue Zu Yanan Liu Lulu Lan Chen Zhu Chengliang Zhang Dong Liu Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression Heliyon Intrahepatic cholestasis Baicalin Pharmacokinetics Accumulation MRP2 |
| title | Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression |
| title_full | Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression |
| title_fullStr | Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression |
| title_full_unstemmed | Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression |
| title_short | Consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing MRP2 expression |
| title_sort | consecutive baicalin treatment relieves its accumulation in rats with intrahepatic cholestasis by increasing mrp2 expression |
| topic | Intrahepatic cholestasis Baicalin Pharmacokinetics Accumulation MRP2 |
| url | http://www.sciencedirect.com/science/article/pii/S2405844022039779 |
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