The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene-3β,6α,12β-triol in MDCK-pHaMDR cell monolayer model

doi:10.5246/jcps.2017.08.063

Abstract

Abstract:

The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene-3β,6α,12β-triol were investigated using the MDCK-pHaMDR cell monolayer model. The bidirectional permeability tests were carried out, and the apparent permeability coefficients (P_app) were calculated. The two protopanaxatriol epimers showed good permeability with P_app values of ~10^–5 cm/s, whereas dammar-20(22)E,24-diene-3β,6α,12β-triol showed poor permeability with P_app of <1×10^–7 cm/s. The three compounds showed differences in intracellular accumulations due to their different structures. Inhibition of P-gp with verapamil showed that the transport mechanisms in MDCK-pHaMDR cell monolayer for compounds 1and 2 epimers were not only simple passive diffusion but also involving an efflux way mediated by P-gp. These findings provided new basis for the further study of compounds 1 and 2 acting on the brain.

Key words: 20(S)-Protopanaxatriol, 20(R)-Protopanaxatriol, Dammar-20(22)E,24-diene-3β,6α,12β-triol, MDCK-pHaMDR, Permeability, Blood-brain barrier

CLC Number:

R284

Supporting:

Yiran Zheng, Xiuwen Wu, Xiuwei Yang. The blood-brain barrier permeability of 20(S) and 20(R)-protopanaxatriol epimers and dammar-20(22)E,24-diene-3β,6α,12β-triol in MDCK-pHaMDR cell monolayer model[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(8): 566-573.

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