Author(s): Zhang J, Zhou F, Wu X, Gu Y, Ai H, et al.
P-glycoprotein (P-gp) is an ATP-dependent efflux transporter highly expressed in gastrointestinal tract and multidrug resistance tumor cells. Inhibition or induction of P-gp can cause drug-drug interactions and thus influence the effects of P-gp substrate drugs. Previous studies indicated that 20(S)-ginsenoside Rh2 [20(S)-Rh2] could synergistically enhance the anticancer effects of conventional chemotherapeutic agents at a nontoxic dose. The aim of present study was to investigate in vitro and in vivo whether 20(S)-Rh2 was a P-gp inhibitor and analyze the possible inhibitory mechanisms and potential herb-drug interactions. Results showed that in vitro, 20(S)-Rh2 significantly enhanced rhodamine 123 retention in cells and decreased the efflux ratio of digoxin, fexofenadine, and etoposide, which were comparable to the effects of the established P-gp inhibitor verapamil. However, the transport of 20(S)-Rh2 suggested that 20(S)-Rh2 was not a P-gp substrate. Furthermore, the inhibitory effect persisted for at least 3 h after removal of 20(S)-Rh2. Unlike P-gp substrates, 20(S)-Rh2 inhibited both basal and verapamil-stimulated P-gp ATPase activities. It also significantly decreased UIC2 binding fluorescence, a marker for conformational change of P-gp. In situ and in vivo experiments showed that 20(S)-Rh2 increased the area under the plasma concentration-time curve and maximum plasma concentration of digoxin, fexofenadine, and etoposide significantly without affecting terminal elimination half-time. Long-term treatment with 20(S)-Rh2 failed to affect intestinal P-gp expression in vitro and in vivo. In conclusion, 20(S)-Rh2 is a potent noncompetitive P-gp inhibitor, which indicates a potential herb-drug interaction when 20(S)-Rh2 is coadministered with P-gp substrate drugs. It could increase the absorption of P-gp substrate drugs without long-term induction of P-gp expression in rats.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/20837659
Author(s): Middleton E Jr, Kandaswami C, Theoharides TC
Author(s): Mozaffarian D, Rimm EB
Author(s): Calder PC, Yaqoob P
Author(s): Zuchi C, Ambrosio G, Luscher TF, Landmesser U
Author(s): Shukla SK, Gupta S, Ojha SK, Sharma SB
Author(s): Ceylan-Isik AF, Fliethman RM, Wold LE, Ren J
Author(s): Hsiao WL, Liu L
Author(s): Chan E, Tan M, Xin J, Sudarsanam S, Johnson DE
Author(s): Xiang YZ, Shang HC, Gao XM, Zhang BL
Author(s): Berman M, Erman A, Ben-Gal T, Dvir D, Georghiou GP, et al.
Author(s): Weant KA, Smith KM
Author(s): Sander S, Coleman CI, Patel AA, Kluger J, White CM
Author(s): Shibata S, Fujita M, Itokawa H, Tanaka O, Ishii T
Author(s): Lu JM, Yao Q, Chen C
Author(s): Deng J, Lv XT, Wu Q, Huang XN
Author(s): Chan RY, Chen WF, Dong A, Guo D, Wong MS
Author(s): Hasegawa H, Uchiyama M
Author(s): Leung KW, Cheung LW, Pon YL, Wong RN, Mak NK, et al.
Author(s): Kitagawa I, Yoshikawa M, Yoshihara M, Hayashi T, Taniyama T
Author(s): Fei XF, Wang BX, Tashiro S, Li TJ, Ma JS, et al.
Author(s): Kim HS, Lee EH, Ko SR, Choi KJ, Park JH, et al.
Author(s): Hasegawa H, Sung JH, Matsumiya S, Uchiyama M, Inouye Y, et al.
Author(s): Jia WW, Bu X, Philips D, Yan H, Liu G, et al.
Author(s): Xie X, Eberding A, Madera C, Fazli L, Jia W, et al.
Author(s): Wang Z, Zheng Q, Liu K, Li G, Zheng R
Author(s): Wang H, Zou H, Kong L, Zhang Y, Pang H, et al.
Author(s): Shangguan D, Han H, Zhao R, Zhao Y, Xiong S, et al.
Author(s): Kwon SW, Han SB, Park IH, Kim JM, Park MK, et al.
Author(s): Li L, Zhang JL, Sheng YX, Ye G, Guo HZ, et al.
Author(s): Yu K, Ma Y, Shao Q, Qu H, Cheng Y
Author(s): Li X, Sun J, Wang G, Hao H, Liang Y, et al.
Author(s): Joo KM, Lee JH, Jeon HY, Park CW, Hong DK, et al.
Author(s): Zhang X, Zhang D, Xu J, Gu J, Zhao Y
Author(s): Yang L, Xu SJ, Zeng X, Liu YM, Deng SG, et al.
Author(s): Qian T, Cai Z, Wong RN, Jiang ZH
Author(s): Xie HT, Wang GJ, Sun JG, Tucker I, Zhao XC, et al.
Author(s): Jiang L, Zhao S, Ya L, Li J
Author(s): Li XW, Gui MY, Zheng Y, Jin YR, Zhang HQ
Author(s): Xie HT, Wang GJ, Lv H, Sun RW, Jiang XL, et al.
Author(s): Gu Y, Wang GJ, Sun JG, Jia YW, Wang W, et al.