title: Elucidation of the Intestinal Absorption Mechanism of Celastrol Using the Caco-2 Cell Transwell Model.
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.
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Hepato-biliary Surgery, Affiliated Hospital of Panzhihua College, Panzhihua, China.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Yili
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Manna
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia and Intensive Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics; D001692:Biological Transport; D018938:Caco-2 Cells; D002352:Carrier Proteins / Q000378:metabolism; D031247:Celastrus / Q000737:chemistry; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D020112:Rhodamine 123 / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014315:Triterpenes / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000972:Antineoplastic Agents, Phytogenic; D002352:Carrier Proteins; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D020112:Rhodamine 123; C050414:celastrol