{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:21:46Z","timestamp":1772781706376,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,2,3]],"date-time":"2019-02-03T00:00:00Z","timestamp":1549152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673626, 81603354, 81703711"],"award-info":[{"award-number":["81673626, 81603354, 81703711"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Eastern Scholar Program","award":["2013-59"],"award-info":[{"award-number":["2013-59"]}]},{"name":"Shanghai E-research Institute of Bioactive Constituent in TCM plan","award":["Shanghai E-research Institute of Bioactive Constituent in TCM plan"],"award-info":[{"award-number":["Shanghai E-research Institute of Bioactive Constituent in TCM plan"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), often reduce drug efficacy and are the major cause of drug resistance. Astragaloside IV (ASIV), one of the bioactive saponins isolated from Astragalus membranaceus, has been demonstrated to alleviate the progression of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model for multiple sclerosis (MS). In the present study, we found for the first time that ASIV induced the upregulation of P-gp and BCRP in the central nervous system (CNS) microvascular endothelial cells of EAE mice. Further study disclosed that tariquidar, a P-gp inhibitor, could facilitate the penetration of ASIV into CNS. On bEnd.3 cells, a mouse brain microvascular endothelial cell line, tariquidar benefited the net uptake and transport of ASIV. Additional molecular docking experiment suggested that ASIV might be a potential substrate of P-gp. In EAE mice, tariquidar was demonstrated to enhance the efficacy of ASIV, as shown by attenuated clinical symptom and reduced incidence rate as well as mitigated inflammatory infiltration and decreased demyelination in the CNS. Collectively, our findings implicate that P-gp inhibitor can promote the therapeutic efficacy of ASIV on EAE mice, which may boost its clinical usage together with ASIV in the therapy of MS.<\/jats:p>","DOI":"10.3390\/molecules24030561","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T11:31:07Z","timestamp":1549366267000},"page":"561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["P-glycoprotein Inhibitor Tariquidar Potentiates Efficacy of Astragaloside IV in Experimental Autoimmune Encephalomyelitis Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines, the Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines, the Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Compound Chinese Medicines, the Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality 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