Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway

Context: Bajijiasu (BJJS), a main bioactive compound from Morinda officinalis F.C. How. (Rubiaceae), is widely administered concomitantly with other drugs for treating male impotence, female infertility, fatigue, chronic rheumatism, depression, etc. Objective: This study investigates the regulation...

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Autores principales:	Xin Yang, Guoyan Hu, Lijuan Lv, Ting Liu, Longkai Qi, Guozhan Huang, Dongqing You, Jun Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	morinda officinalis f.c. how keap1 transport protein herb–drug interaction Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/11a2e44feba7493f853385dd6507b565
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spelling	oai:doaj.org-article:11a2e44feba7493f853385dd6507b5652021-11-17T14:21:56ZRegulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway1388-02091744-511610.1080/13880209.2019.1582679https://doaj.org/article/11a2e44feba7493f853385dd6507b5652019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1582679https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: Bajijiasu (BJJS), a main bioactive compound from Morinda officinalis F.C. How. (Rubiaceae), is widely administered concomitantly with other drugs for treating male impotence, female infertility, fatigue, chronic rheumatism, depression, etc. Objective: This study investigates the regulation of P-glycoprotein (P-gp) by BJJS in vitro and in vivo. Material and methods: HepG2 cells were incubated with BJJS (10, 20 or 40 μM) for 48 h. C57 mice were orally treated with BJJS (25, 50 or 100 mg/kg) for 2 weeks. The protein and mRNA levels of P-gp were measured by using Western blot and real-time PCR, respectively. siNrf2 RNA was used to explore the mediation effects of Nrf2 on the P-gp expression. The efflux activity of P-gp was tested via a flow cytometry. Results: Incubation of HepG2 cells with BJJS at 10, 20, and 40 μM up-regulated the P-gp protein expression by 12.3%, 82.9%, and 134.3%, respectively. Treatment of C57 mice with BJJS at 25, 50 and 100 mg/kg increased the P-gp protein expression by 49.3%, 75.8% and 106.0%, respectively. Incubation of the cells with BJJS at 10, 20 and 40 μM up-regulated the total Nrf2 protein levels by 34.3%, 93.1% and 118.6%, respectively, and also increased the nuclear Nrf2 protein levels by 14.8%, 44.4% and 59.25%, respectively. The total Nrf2 protein levels were increased by 46.3%, 66.5%, and 87.4%, respectively, in the mice exposed to BJJS at 25, 50, and 100 mg/kg. Inhibition of Nrf2 by siRNA diminished the P-gp induction by 25.0%, 33.4%, and 38.7%, respectively, in the cells. In addition, BJJS enhanced the efflux activity of P-gp by 9.6%, 37.1%, and 48.1%, respectively, in the cells. Conclusions: BJJS activates Nrf2 to induce P-gp expression, and enhanced the efflux activity of P-gp. The possibility of potential herb–drug interactions when BJJS is co-administered with other P-gp substrate drugs should be carefully monitored.Xin YangGuoyan HuLijuan LvTing LiuLongkai QiGuozhan HuangDongqing YouJun ZhaoTaylor & Francis Grouparticlemorinda officinalis f.c. howkeap1transport proteinherb–drug interactionTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 184-192 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	morinda officinalis f.c. how keap1 transport protein herb–drug interaction Therapeutics. Pharmacology RM1-950
spellingShingle	morinda officinalis f.c. how keap1 transport protein herb–drug interaction Therapeutics. Pharmacology RM1-950 Xin Yang Guoyan Hu Lijuan Lv Ting Liu Longkai Qi Guozhan Huang Dongqing You Jun Zhao Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
description	Context: Bajijiasu (BJJS), a main bioactive compound from Morinda officinalis F.C. How. (Rubiaceae), is widely administered concomitantly with other drugs for treating male impotence, female infertility, fatigue, chronic rheumatism, depression, etc. Objective: This study investigates the regulation of P-glycoprotein (P-gp) by BJJS in vitro and in vivo. Material and methods: HepG2 cells were incubated with BJJS (10, 20 or 40 μM) for 48 h. C57 mice were orally treated with BJJS (25, 50 or 100 mg/kg) for 2 weeks. The protein and mRNA levels of P-gp were measured by using Western blot and real-time PCR, respectively. siNrf2 RNA was used to explore the mediation effects of Nrf2 on the P-gp expression. The efflux activity of P-gp was tested via a flow cytometry. Results: Incubation of HepG2 cells with BJJS at 10, 20, and 40 μM up-regulated the P-gp protein expression by 12.3%, 82.9%, and 134.3%, respectively. Treatment of C57 mice with BJJS at 25, 50 and 100 mg/kg increased the P-gp protein expression by 49.3%, 75.8% and 106.0%, respectively. Incubation of the cells with BJJS at 10, 20 and 40 μM up-regulated the total Nrf2 protein levels by 34.3%, 93.1% and 118.6%, respectively, and also increased the nuclear Nrf2 protein levels by 14.8%, 44.4% and 59.25%, respectively. The total Nrf2 protein levels were increased by 46.3%, 66.5%, and 87.4%, respectively, in the mice exposed to BJJS at 25, 50, and 100 mg/kg. Inhibition of Nrf2 by siRNA diminished the P-gp induction by 25.0%, 33.4%, and 38.7%, respectively, in the cells. In addition, BJJS enhanced the efflux activity of P-gp by 9.6%, 37.1%, and 48.1%, respectively, in the cells. Conclusions: BJJS activates Nrf2 to induce P-gp expression, and enhanced the efflux activity of P-gp. The possibility of potential herb–drug interactions when BJJS is co-administered with other P-gp substrate drugs should be carefully monitored.
format	article
author	Xin Yang Guoyan Hu Lijuan Lv Ting Liu Longkai Qi Guozhan Huang Dongqing You Jun Zhao
author_facet	Xin Yang Guoyan Hu Lijuan Lv Ting Liu Longkai Qi Guozhan Huang Dongqing You Jun Zhao
author_sort	Xin Yang
title	Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
title_short	Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
title_full	Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
title_fullStr	Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
title_full_unstemmed	Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway
title_sort	regulation of p-glycoprotein by bajijiasu in vitro and in vivo by activating the nrf2-mediated signalling pathway
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/11a2e44feba7493f853385dd6507b565
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Regulation of P-glycoprotein by Bajijiasu in vitro and in vivo by activating the Nrf2-mediated signalling pathway

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