%0 Journal Article
%T Sesquiterpene dimers with a rare skeleton from Chloranthus holostegius exhibiting multidrug resistance reversal activity in vitro and in vivo.
%A Wang S
%A Hou J
%A Jiang H
%A Lee D
%A Xu J
%A Guo Y
%J Fitoterapia
%V 177
%N 0
%D 2024 Sep 15
%M 39019239
%F 3.204
%R 10.1016/j.fitote.2024.106125
%X Two previously unreported lindenane sesquiterpene dimers (1 and 2) with a rare skeleton containing an oxaspiro[4.5]decane moiety were isolated from the roots of Chloranthus holostegius var. trichoneurus. Their structures were elucidated by HRESIMS, NMR, ECD, and NMR quantum chemical calculations, along with DP4+ probability analysis. In bioassay, compound 1 exhibited significant activity to reverse the multidrug resistance (MDR)in MCF-7/ADR cells, with an IC50 value of 4.4 μM. Further mechanistic studies revealed that compound 1 combined with doxorubicin could induce apoptosis of MCF-7/ADR cells and block the cell cycle in the G2/M phase. Mechanistically, compound 1 could inhibit the efflux function of P-glycoprotein (P-gp) using the zebrafish model. Finally, the enhanced chemotherapeutic effects of doxorubicin were further confirmed by in vivo zebrafish xenograft experiments.