Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages.
<h4>Background</h4>HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibitin...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/48ba76f137a34e8ab09360090c8231ae |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:48ba76f137a34e8ab09360090c8231ae |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:48ba76f137a34e8ab09360090c8231ae2021-11-18T08:00:22ZInhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages.1932-620310.1371/journal.pone.0054349https://doaj.org/article/48ba76f137a34e8ab09360090c8231ae2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23372711/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER) stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages.<h4>Methodology and principal findings</h4>Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT) and human P-gp transfected (MDCK/P-gp) cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123) efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp.<h4>Conclusion and significance</h4>HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic.Weibin ZhaGuangji WangWeiren XuXuyuan LiuYun WangBeth S ZhaJian ShiQijin ZhaoPhillip M GerkElaine StuderPhillip B HylemonWilliam M PandakHuiping ZhouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54349 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Weibin Zha Guangji Wang Weiren Xu Xuyuan Liu Yun Wang Beth S Zha Jian Shi Qijin Zhao Phillip M Gerk Elaine Studer Phillip B Hylemon William M Pandak Huiping Zhou Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| description |
<h4>Background</h4>HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER) stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages.<h4>Methodology and principal findings</h4>Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT) and human P-gp transfected (MDCK/P-gp) cells were used in this study. The intracellular concentration of BBR was determined by HPLC. The activity of P-gp was assessed by measuring digoxin and rhodamine 123 (Rh123) efflux. The interaction between P-gp and BBR or HIV PIs was predicated by Glide docking using Schrodinger program. The results indicate that P-gp contributed to the efflux of BBR in macrophages. HIV PIs significantly increased BBR concentrations in macrophages; however, BBR did not alter cellular HIV PI concentrations. Although HIV PIs did not affect P-gp expression, P-gp transport activities were significantly inhibited in HIV PI-treated macrophages. Furthermore, the molecular docking study suggests that both HIV PIs and BBR fit the binding pocket of P-gp, and HIV PIs may compete with BBR to bind P-gp.<h4>Conclusion and significance</h4>HIV PIs increase the concentration of BBR by modulating the transport activity of P-gp in macrophages. Understanding the cellular mechanisms of potential drug-drug interactions is critical prior to applying successful combinational therapy in the clinic. |
| format |
article |
| author |
Weibin Zha Guangji Wang Weiren Xu Xuyuan Liu Yun Wang Beth S Zha Jian Shi Qijin Zhao Phillip M Gerk Elaine Studer Phillip B Hylemon William M Pandak Huiping Zhou |
| author_facet |
Weibin Zha Guangji Wang Weiren Xu Xuyuan Liu Yun Wang Beth S Zha Jian Shi Qijin Zhao Phillip M Gerk Elaine Studer Phillip B Hylemon William M Pandak Huiping Zhou |
| author_sort |
Weibin Zha |
| title |
Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| title_short |
Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| title_full |
Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| title_fullStr |
Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| title_full_unstemmed |
Inhibition of P-glycoprotein by HIV protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| title_sort |
inhibition of p-glycoprotein by hiv protease inhibitors increases intracellular accumulation of berberine in murine and human macrophages. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/48ba76f137a34e8ab09360090c8231ae |
| work_keys_str_mv |
AT weibinzha inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT guangjiwang inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT weirenxu inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT xuyuanliu inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT yunwang inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT bethszha inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT jianshi inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT qijinzhao inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT phillipmgerk inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT elainestuder inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT phillipbhylemon inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT williammpandak inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages AT huipingzhou inhibitionofpglycoproteinbyhivproteaseinhibitorsincreasesintracellularaccumulationofberberineinmurineandhumanmacrophages |
| _version_ |
1718422660979884032 |