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Planta Med 2016; 82(13): 1202-1207
DOI: 10.1055/s-0035-1568597
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Elucidation of the Intestinal Absorption Mechanism of Celastrol Using the Caco-2 Cell Transwell Model

Hong Li   *
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Jie Li   *
2   Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
3   Department of Anesthesiology, Putuo District Maternal and Child Health Hospital, Shanghai, China
,
Lu Liu   *
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Yichuan Zhang
4   Department of Hepato-biliary Surgery, Affiliated Hospital of Panzhihua College, Panzhihua, China
,
Yili Luo
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Xiaoli Zhang
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Peng Yang
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Manna Zhang
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
,
Weifeng Yu
2   Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
,
Shen Qu
1   Department of Endocrinology, Shanghai Tenth Peopleʼs Hospital, Tongji University School of Medicine, Shanghai, China
› Author Affiliations
Further Information

Publication History

received 26 September 2015
revised 01 April 2016

accepted 05 April 2016

Publication Date:
09 May 2016 (online)

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Erratum for: Elucidation of the Intestinal Absorption Mechanism of Celastrol Using the Caco-2 Cell Transwell ModelPlanta Med 2016; 82(13): E6-E6
DOI: 10.1055/s-0036-1585129

Abstract

Celastrol, a triterpenoid isolated from stem (caulis) of Celastrus orbiculatus Thunb. (Celastraceae), has been known to have various pharmacological effects, including anti-inflammatory, anticancer, and antioxidant activities. However, the mechanism of the intestinal absorption of celastrol is unknown. The aim of this study was to investigate the intestinal absorption of celastrol using the Caco-2 cell transwell model. First, the bidirectional transport of celastrol in Caco-2 cell monolayers was observed. Then, the effects of time, concentration, temperature, paracellular pathway, and efflux transport inhibition on the transport of celastrol across the Caco-2 cell monolayers were investigated. The P-glycoprotein inhibitor verapamil and cyclosporin A, the multidrug resistance protein 2 inhibitor MK571, and the breast cancer resistance protein inhibitor reserpine were used. Additionally, the effects of celastrol on the activity of P-glycoprotein were evaluated using the rhodamine 123 uptake assay. In this study, we found that the intestinal transport of celastrol was a time- and concentration-dependent active transport. The paracellular pathway was not involved in the transport of celastrol, and the efflux of celastrol was energy dependent. The results indicated that celastrol is a substrate of P-glycoprotein but not multidrug resistance protein 2 or the breast cancer resistance protein. In addition, celastrol could not affect the uptake of rhodamine 123 in Caco-2 cells, which indicated that celastrol could not inhibit or induce the activity of P-glycoprotein.

Key words

Celastrus orbiculatus Thunb. - BCRP - Caco-2 cell - celastrol - MRP2 - P-gp

* The first three authors contributed equally to this work.


 

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