Mechanistic studies of the transport of peimine in the Caco-2 cell model
Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of th...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-03-01
|
| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383515300903 |
| _version_ | 1818505417299329024 |
|---|---|
| author | Lihua Chen Xueping Lu Xinli Liang Dandan Hong Zhiyu Guan Yongmei Guan Weifeng Zhu |
| author_facet | Lihua Chen Xueping Lu Xinli Liang Dandan Hong Zhiyu Guan Yongmei Guan Weifeng Zhu |
| author_sort | Lihua Chen |
| collection | DOAJ |
| description | Fritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 μmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the Papp(AP-BL) of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL) and Papp(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp. |
| first_indexed | 2024-12-10T21:50:30Z |
| format | Article |
| id | doaj.art-f525f4320fcd481693b40fcb89b1ef19 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 2211-3843 |
| language | English |
| last_indexed | 2024-12-10T21:50:30Z |
| publishDate | 2016-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-f525f4320fcd481693b40fcb89b1ef192022-12-22T01:32:14ZengElsevierActa Pharmaceutica Sinica B2211-38352211-38432016-03-016212513110.1016/j.apsb.2016.01.006Mechanistic studies of the transport of peimine in the Caco-2 cell modelLihua ChenXueping LuXinli LiangDandan HongZhiyu GuanYongmei GuanWeifeng ZhuFritillaria thunbergii Miq. has been widely used in traditional Chinese medicine for its expectorant, antitussive, antiinflammatory and analgesic properties. Moreover, modern pharmacological studies have demonstrated that F. thunbergii Miq. has efficacy in the treatment of leukemia and cancers of the liver and cervix. Although the alkaloid, peimine, is largely responsible for these pharmacological effects, it has very low oral bioavailability. The aim of this study was to investigate the intestinal absorption of peimine in Caco-2 cell monolayers. Having demonstrated that peimine is non-toxic to Caco-2 cells at concentrations <200 μmol/L, the effect of peimine concentration, pH, temperature, efflux transport protein inhibitors and EDTA-Na2 on peimine transport were studied. The results show that peimine transport is concentration-dependent; that at pH 6.0 and 7.4, the Papp(AP-BL) of peimine is not significantly different but the Papp(BL-AP)) is; that both Papp(AP-BL) and Papp(BL-AP) at 4 °C are significantly higher than their corresponding values at 37 °C; that the P-glycoprotein (P-gp) inhibitors, verapamil and cyclosporin A, increase absorption of peimine; and that EDTA-Na2 has no discernible effect. In summary, the results demonstrate that the intestinal absorption of peimine across Caco-2 cell monolayers involves active transport and that peimine is a substrate of P-gp.http://www.sciencedirect.com/science/article/pii/S2211383515300903PeimineIntestinal absorptionCaco-2 cell monolayerP-glycoproteinTransport mechanism |
| spellingShingle | Lihua Chen Xueping Lu Xinli Liang Dandan Hong Zhiyu Guan Yongmei Guan Weifeng Zhu Mechanistic studies of the transport of peimine in the Caco-2 cell model Acta Pharmaceutica Sinica B Peimine Intestinal absorption Caco-2 cell monolayer P-glycoprotein Transport mechanism |
| title | Mechanistic studies of the transport of peimine in the Caco-2 cell model |
| title_full | Mechanistic studies of the transport of peimine in the Caco-2 cell model |
| title_fullStr | Mechanistic studies of the transport of peimine in the Caco-2 cell model |
| title_full_unstemmed | Mechanistic studies of the transport of peimine in the Caco-2 cell model |
| title_short | Mechanistic studies of the transport of peimine in the Caco-2 cell model |
| title_sort | mechanistic studies of the transport of peimine in the caco 2 cell model |
| topic | Peimine Intestinal absorption Caco-2 cell monolayer P-glycoprotein Transport mechanism |
| url | http://www.sciencedirect.com/science/article/pii/S2211383515300903 |
| work_keys_str_mv | AT lihuachen mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT xuepinglu mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT xinliliang mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT dandanhong mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT zhiyuguan mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT yongmeiguan mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel AT weifengzhu mechanisticstudiesofthetransportofpeimineinthecaco2cellmodel |