{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:55:53Z","timestamp":1792072553290,"version":"4.4.0"},"reference-count":262,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Multidrug resistance (MDR) is regarded as one of the bottlenecks of successful clinical treatment for numerous chemotherapeutic agents. Multiple key regulators are alleged to be responsible for MDR and making the treatment regimens ineffective. In this review, we discuss MDR in relation to P-glycoprotein (P-gp) and its down-regulation by natural bioactive molecules. P-gp, a unique ATP-dependent membrane transport protein, is one of those key regulators which are present in the lining of the colon, endothelial cells of the blood brain barrier (BBB), bile duct, adrenal gland, kidney tubules, small intestine, pancreatic ducts and in many other tissues like heart, lungs, spleen, skeletal muscles, etc. Due to its diverse tissue distribution, P-gp is a novel protective barrier to stop the intake of xenobiotics into the human body. Over-expression of P-gp leads to decreased intracellular accretion of many chemotherapeutic agents thus assisting in the development of MDR. Eventually, the effectiveness of these drugs is decreased. P-gp inhibitors act by altering intracellular ATP levels which are the source of energy and\/or by affecting membrane contours to increase permeability. However, the use of synthetic inhibitors is known to cause serious toxicities. For this reason, the search for more potent and less toxic P-gp inhibitors of natural origin is underway. The present review aims to recapitulate the research findings on bioactive constituents of natural origin with P-gp inhibition characteristics. Natural bioactive constituents with P-gp modulating effects offer great potential for semi-synthetic modification to produce new scaffolds which could serve as valuable investigative tools to recognize the function of complex ABC transporters apart from evading the systemic toxicities shown by synthetic counterparts. Despite the many published scientific findings encompassing P-gp inhibitors, however, this article stand alones because it provides a vivid picture to the readers pertaining to Pgp inhibitors obtained from natural sources coupled with their mode of action and structures. It provides first-hand information to the scientists working in the field of drug discovery to further synthesise and discover new P-gp inhibitors with less toxicity and more efficacies.<\/jats:p>","DOI":"10.3390\/molecules22060871","type":"journal-article","created":{"date-parts":[[2017,5,30]],"date-time":"2017-05-30T04:35:42Z","timestamp":1496118942000},"page":"871","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":194,"title":["Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9085-4226","authenticated-orcid":false,"given":"Saikat","family":"Dewanjee","sequence":"first","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarun","family":"Dua","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloy","family":"Bhattacharjee","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anup","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, ADAMAS University, Barasat, Kolkata 700126, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moumita","family":"Gangopadhyay","sequence":"additional","affiliation":[{"name":"Department of Bioechnology, ADAMAS University, Barasat, Kolkata 700126, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ritu","family":"Khanra","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarnalata","family":"Joardar","sequence":"additional","affiliation":[{"name":"Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Raja S C Mullick Road, Kolkata 700032, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9327-1368","authenticated-orcid":false,"given":"Muhammad","family":"Riaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal 18050, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1070-3207","authenticated-orcid":false,"given":"Vincenzo","family":"Feo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Salerno University, Fisciano 84084, Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Zia-Ul-Haq","sequence":"additional","affiliation":[{"name":"Environment Science Department, Lahore College for Women University, Jail Road, Lahore 54600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/jcp.1040830114","article-title":"Reduced permeability in CHO cells as a mechanism of resistance to colchicine","volume":"83","author":"Ling","year":"1974","journal-title":"J. Cell. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00424-006-0126-x","article-title":"Structure and function of ABC transporters: The ATP switch provides flexible control","volume":"453","author":"Linton","year":"2007","journal-title":"Eur. J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0304-3835(00)00549-8","article-title":"Inhibition of P-glycoprotein by orange juice components, polymethoxyflavones in adriamycin-resistant human myelogenous leukemia (K562\/ADM) cells","volume":"160","author":"Ikegawa","year":"2000","journal-title":"Cancer Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.biopha.2015.01.007","article-title":"Effects of natural nuclear factor-kappa \u03b2 inhibitors on anticancer drug efflux transporter human P-glycoprotein","volume":"70","author":"Nabekura","year":"2015","journal-title":"Biomed. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46","DOI":"10.18433\/J3RC77","article-title":"Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy","volume":"12","author":"Bansal","year":"2009","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.fct.2006.07.003","article-title":"Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products","volume":"44","author":"Yoshida","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3390\/md12010525","article-title":"Marine natural products with P-glycoprotein inhibitor properties","volume":"12","author":"Lopez","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2174\/1389557053402756","article-title":"Efflux transporters and their clinical relevance","volume":"5","author":"Fischer","year":"2005","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0092-8674(00)81370-7","article-title":"Mdr1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine","volume":"87","author":"Smith","year":"1996","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23530","DOI":"10.1074\/jbc.M909002199","article-title":"MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping","volume":"275","author":"Smith","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_11","first-page":"1","article-title":"Multidrug resistance in the laboratory and clinic","volume":"31","author":"Bellamy","year":"1993","journal-title":"Adv. Clin. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1073\/pnas.87.1.152","article-title":"Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies","volume":"87","author":"Georges","year":"1990","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","first-page":"1549","article-title":"Multi-drug resistance (MDR) activity in acute leukemia determined by rhodamine 123 efflux assay","volume":"9","author":"Lamy","year":"1995","journal-title":"Leukemia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/bjc.1993.177","article-title":"Constitutive expression of multidrug resistance in human colorectal tumours and cell lines","volume":"67","author":"Kramer","year":"1993","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1093\/jnci\/81.18.1401","article-title":"Correlation of mdr1 gene expression with chemotherapy in neuroblastoma","volume":"81","author":"Bourhis","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1365-2141.1991.tb04378.x","article-title":"Expression of the multidrug resistance gene product (P-glycoprotein) in myelodysplasia is associated with a stem cell phenotype","volume":"78","author":"List","year":"1991","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/0145-2126(93)90159-I","article-title":"Detection of p glycoprotein activity on normal and leukemic cd34+ cells","volume":"17","author":"Drenou","year":"1993","journal-title":"Leuk. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1093\/jnci\/81.15.1144","article-title":"mdr1 gene expression in lung cancer","volume":"81","author":"Lai","year":"1989","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_19","first-page":"1422","article-title":"Expression of anionic glutathione-s-transferase and P-glycoprotein genes in human tissues and tumors","volume":"49","author":"Moscow","year":"1989","journal-title":"Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1182\/blood.V78.3.586.586","article-title":"Multidrug resistance (mdr1) gene expression in adult acute leukemias: Correlations with treatment outcome and in vitro drug sensitivity","volume":"78","author":"Marie","year":"1991","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1200\/JCO.1993.11.1.109","article-title":"Expression of P-glycoprotein and glutathione-s-transferase in recurrent lymphomas: The possible role of Epstein-Barr virus, immunophenotypes, and other predisposing factors","volume":"11","author":"Cheng","year":"1993","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1043-6618(03)00158-0","article-title":"P-glycoprotein inhibitors and their screening: A perspective from bioavailability enhancement","volume":"48","author":"Varma","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7735","DOI":"10.1073\/pnas.84.21.7735","article-title":"Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues","volume":"84","author":"Thiebaut","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1016\/0006-2952(94)90209-7","article-title":"Expression and function of multidrug resistance P-glycoprotein in a cultured natural killer cell-rich population revealed by mrk16 monoclonal antibody and AHC-52","volume":"48","author":"Kobayashi","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0092-8674(91)90141-K","article-title":"Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells","volume":"66","author":"Chaudhary","year":"1991","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1369\/jhc.5A6870.2006","article-title":"In situ localization of P-glycoprotein (ABCB1) in human and rat brain","volume":"54","author":"Bendayan","year":"2006","journal-title":"J. Histochem. Cytochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/S0014-5793(03)01085-8","article-title":"Multidrug resistance ABC transporters","volume":"555","author":"Chang","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0924-8579(03)00203-6","article-title":"ABC-transporters: Implications on drug resistance from microorganisms to human cancers","volume":"22","author":"Lage","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0923-2508(01)01193-7","article-title":"ABC transporters: Physiology, structure and mechanism\u2014An overview","volume":"152","author":"Higgins","year":"2001","journal-title":"Res. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3743","DOI":"10.1128\/AAC.48.10.3743-3748.2004","article-title":"Acquired bacitracin resistance in Enterococcus faecalis is mediated by an ABC transporter and a novel regulatory protein, bcrr","volume":"48","author":"Manson","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.bcp.2005.10.021","article-title":"Efflux systems in bacterial pathogens: An opportunity for therapeutic intervention? An industry view","volume":"71","author":"Lynch","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.molmed.2005.06.006","article-title":"Inhibitors of efflux pumps in gram-negative bacteria","volume":"11","author":"Masi","year":"2005","journal-title":"Trends Mol. Med."},{"key":"ref_33","first-page":"257","article-title":"The major facilitator superfamily","volume":"1","author":"Saier","year":"1999","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1208\/aapsj070101","article-title":"Characterization of the human mdr1 gene","volume":"7","author":"Bodor","year":"2005","journal-title":"AAPS J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.bbrc.2005.01.134","article-title":"Do drug substrates enter the common drug-binding pocket of P-glycoprotein through \u201cgates\u201d?","volume":"329","author":"Loo","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13660","DOI":"10.1021\/bi9808823","article-title":"Structural flexibility of the linker region of human P-glycoprotein permits ATP hydrolysis and drug transport","volume":"37","author":"Hrycyna","year":"1998","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/25393","article-title":"Crystal structure of the ATP-binding subunit of an ABC transporter","volume":"396","author":"Hung","year":"1998","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5518","DOI":"10.1021\/bi992931x","article-title":"Analysis of the properties of the n-terminal nucleotide-binding domain of human P-glycoprotein","volume":"39","author":"Booth","year":"2000","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5363","DOI":"10.1074\/jbc.M311964200","article-title":"Synergy between conserved abc signature ser residues in P-glycoprotein catalysis","volume":"279","author":"Tombline","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.taap.2005.04.001","article-title":"Inhibition of P-glycoprotein-mediated transport by extracts of and monoterpenoids contained in zanthoxyli fructus","volume":"209","author":"Yoshida","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1146\/annurev.pharmtox.39.1.361","article-title":"Biochemical, cellular, and pharmacological aspects of the multidrug transporter 1","volume":"39","author":"Ambudkar","year":"1999","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/scbi.1997.0066","article-title":"How does P-glycoprotein recognize its substrates?","volume":"8","author":"Ueda","year":"1997","journal-title":"Semin. Cancer Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2522","DOI":"10.1074\/jbc.M411483200","article-title":"The dileucine motif at the cooh terminus of human multidrug resistance P-glycoprotein is important for folding but not activity","volume":"280","author":"Loo","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7692","DOI":"10.1074\/jbc.M311825200","article-title":"Disulfide cross-linking analysis shows that transmembrane segments 5 and 8 of human P-glycoprotein are close together on the cytoplasmic side of the membrane","volume":"279","author":"Loo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"18232","DOI":"10.1074\/jbc.M400229200","article-title":"Val133 and cys137 in transmembrane segment 2 are close to ARG935 and GLY939 in transmembrane segment 11 of human P-glycoprotein","volume":"279","author":"Loo","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00232-005-0792-1","article-title":"Recent progress in understanding the mechanism of P-glycoprotein-mediated drug efflux","volume":"206","author":"Loo","year":"2005","journal-title":"J. Membr. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2006.10.007","article-title":"A primer on the mechanics of P-glycoprotein the multidrug transporter","volume":"55","author":"Hennessy","year":"2007","journal-title":"Pharmacol. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/0968-0004(92)90419-A","article-title":"Is the multidrug transporter a flippase?","volume":"17","author":"Higgins","year":"1992","journal-title":"Trends Biochem. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1590\/S1984-82502012000300002","article-title":"Overview of P-glycoprotein inhibitors: A rational outlook","volume":"48","author":"Srivalli","year":"2012","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.bcp.2005.12.008","article-title":"Practical applications and feasibility of efflux pump inhibitors in the clinic\u2014A vision for applied use","volume":"71","author":"Lomovskaya","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrd2200","article-title":"Waltzing transporters and \u2018the dance macabre \u2018between humans and bacteria","volume":"6","author":"Lomovskaya","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1158\/1078-0432.CCR-06-2414","article-title":"A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (gf120918) and oral topotecan in cancer patients","volume":"13","author":"Kuppens","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/cncr.21227","article-title":"Phase ii study of tariquidar, a selective P-glycoprotein inhibitor, in patients with chemotherapy-resistant, advanced breast carcinoma","volume":"104","author":"Pusztai","year":"2005","journal-title":"Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0928-0987(00)00114-7","article-title":"Multidrug resistance (MDR) in cancer: Mechanisms, reversal using modulators of mdr and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs","volume":"11","author":"Krishna","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"326","DOI":"10.2174\/15680096113139990076","article-title":"P-glycoprotein inhibition as a therapeutic approach for overcoming multidrug resistance in cancer: Current status and future perspectives","volume":"13","author":"Binkhathlan","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2133\/dmpk.DMPK-11-RV-098","article-title":"Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2)","volume":"27","author":"Ieiri","year":"2012","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/bdd.593","article-title":"Effects of oral kaempferol on the pharmacokinetics of tamoxifen and one of its metabolites, 4-hydroxytamoxifen, after oral administration of tamoxifen to rats","volume":"29","author":"Piao","year":"2008","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1016\/j.lfs.2005.12.009","article-title":"Evidence-based drug\u2013herbal interactions","volume":"78","author":"Chavez","year":"2006","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.drudis.2007.06.004","article-title":"Identification of drugs that interact with herbs in drug development","volume":"12","author":"Zhou","year":"2007","journal-title":"Drug Discov. Today"},{"key":"ref_60","first-page":"176","article-title":"An in vitro evaluation of human cytochrome p450 3a4 and P-glycoprotein inhibition by garlic","volume":"4","author":"Foster","year":"2001","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s12038-010-0065-8","article-title":"Antimycobacterial activity of two natural alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian shrub Adhatoda vasica Ness. leaves","volume":"35","author":"Ignacimuthu","year":"2010","journal-title":"J. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/ptr.2136","article-title":"Antibacterial activity of two canthin-6-one alkaloids from Allium neapolitanum","volume":"21","author":"Gibbons","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_63","first-page":"455","article-title":"Modulation of multidrug resistance by three bisbenzyl-isoquinolines in comparison with verapamil","volume":"18","author":"Tian","year":"1997","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8369","DOI":"10.1073\/pnas.95.14.8369","article-title":"Reversal of anticancer multidrug resistance by the ardeemins","volume":"95","author":"Chou","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","first-page":"47","article-title":"Fumitremorgin c reverses multidrug resistance in cells transfected with the breast cancer resistance protein","volume":"60","author":"Rabindran","year":"2000","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s002800050592","article-title":"Induction of apoptosis in multi-drug resistant (mdr) human glioblastoma cells by sn-38, a metabolite of the camptothecin derivative cpt-11","volume":"39","author":"Nakatsu","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_67","first-page":"1653","article-title":"Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells","volume":"3","author":"Gupta","year":"1997","journal-title":"Clin. Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1248\/bpb.33.255","article-title":"Effects of dietary ingredients on function and expression of P-glycoprotein in human intestinal epithelial cells","volume":"33","author":"Okura","year":"2010","journal-title":"Biol. Pharm. Bull."},{"key":"ref_69","first-page":"591","article-title":"Effects of various principles from Chinese herbal medicine on rhodamine123 accumulation in brain capillary endothelial cells","volume":"23","author":"He","year":"2002","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/tox.20568","article-title":"Hydrocinchonine, cinchonine, and quinidine potentiate paclitaxel-induced cytotoxicity and apoptosis via multidrug resistance reversal in MES-SA\/DX5 uterine sarcoma cells","volume":"26","author":"Lee","year":"2011","journal-title":"Environ. Toxicol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1038\/sj.leu.2401945","article-title":"Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the chvp regimen in relapsed and refractory lymphoproliferative syndromes","volume":"14","author":"Solary","year":"2000","journal-title":"Leukemia"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1124\/jpet.102.037549","article-title":"Interaction of cytochrome P450 A inhibitors with P-glycoprotein","volume":"303","author":"Yasuda","year":"2002","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1055\/s-2008-1074518","article-title":"Phytochemicals for bacterial resistance-strengths, weaknesses and opportunities","volume":"74","author":"Gibbons","year":"2008","journal-title":"Planta Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/BF02974076","article-title":"Protoberberine alkaloids and their reversal activity of P-gp expressed multidrug resistance (MDR) from the rhizome of Coptis japonica Makino","volume":"29","author":"Min","year":"2006","journal-title":"Arch. Pharm. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.foodchem.2012.09.059","article-title":"An isoquinoline alkaloid from the Chinese herbal plant Corydalis yanhusuo wt wang inhibits P-glycoprotein and multidrug resistance-associate protein 1","volume":"136","author":"Lei","year":"2013","journal-title":"Food Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11010-015-2339-9","article-title":"Glaucine inhibits breast cancer cell migration and invasion by inhibiting mmp-9 gene expression through the suppression of NF-\u03baB activation","volume":"403","author":"Kang","year":"2015","journal-title":"Mol. Cell. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1016\/j.fct.2011.11.008","article-title":"Anti-proliferative activity and suppression of P-glycoprotein by (\u2212)-antofine, a natural phenanthroindolizidine alkaloid, in paclitaxel-resistant human lung cancer cells","volume":"50","author":"Kim","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1021\/jo00302a006","article-title":"Antitumor tetrahydroisoquinoline alkaloids from the colonial ascidian Ecteinascidia turbinata","volume":"55","author":"Wright","year":"1990","journal-title":"J. Org. Chem."},{"key":"ref_79","first-page":"1327","article-title":"Overcoming multidrug drug resistance in P-glycoprotein\/mdr1-overexpressing cell lines by ecteinascidin 743","volume":"1","author":"Kanzaki","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_80","first-page":"4030","article-title":"Pervilleine A, a novel tropane alkaloid that reverses the multidrug-resistance phenotype","volume":"61","author":"Mi","year":"2001","journal-title":"Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0026-895X(25)08534-7","article-title":"Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance","volume":"47","author":"Smith","year":"1995","journal-title":"Mol. Pharmacol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/152165401317291183","article-title":"Transfer of cationic antibacterial agents berberine, palmatine, and benzalkonium through bimolecular planar phospholipid film and Staphylococcus aureus membrane","volume":"52","author":"Severina","year":"2001","journal-title":"IUBMB Life"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/cbdd.12103","article-title":"Antibacterial and synergy of clavine alkaloid lysergol and its derivatives against nalidixic acid-resistant Escherichia coli","volume":"81","author":"Maurya","year":"2013","journal-title":"Chem. Biol. Drug Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1055\/s-1999-13991","article-title":"Reversal of multidrug resistance by kopsiflorine isolated from Kopsia dasyrachis","volume":"65","author":"Rho","year":"1999","journal-title":"Planta Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0960-894X(98)00486-7","article-title":"Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids","volume":"8","author":"Kam","year":"1998","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/bjc.1996.421","article-title":"Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein","volume":"74","author":"Quesada","year":"1996","journal-title":"Br. J. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/0304-3835(93)90103-G","article-title":"A marine natural product, patellamide d, reverses multidrug resistance in a human leukemic cell line","volume":"71","author":"Williams","year":"1993","journal-title":"Cancer Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1021\/np9802872","article-title":"New cyclic peptides from the ascidian Lissoclinum patella","volume":"61","author":"Fu","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4621","DOI":"10.1021\/ol801895y","article-title":"A new total synthesis of patellamide A","volume":"10","author":"VanNieuwenhze","year":"2008","journal-title":"Org. Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.phymed.2007.11.028","article-title":"Lobeline, a piperidine alkaloid from Lobelia can reverse P-gp dependent multidrug resistance in tumor cells","volume":"15","author":"Ma","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2010","DOI":"10.3390\/md13042010","article-title":"Marine natural products as breast cancer resistance protein inhibitors","volume":"13","author":"Cherigo","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1158\/1535-7163.MCT-06-0811","article-title":"Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure","volume":"6","author":"Robey","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.bmcl.2006.12.059","article-title":"N-caffeoylphenalkylamide derivatives as bacterial efflux pump inhibitors","volume":"17","author":"Michalet","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00284-009-9416-9","article-title":"Inhibitory and resistance-modifying potential of plant-based alkaloids against methicillin-resistant Staphylococcus aureus (mrsa)","volume":"59","author":"Mohtar","year":"2009","journal-title":"Curr. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1002\/ptr.2860","article-title":"The beta-carboline alkaloid harmine inhibits bcrp and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells","volume":"24","author":"Ma","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.phymed.2013.07.019","article-title":"Influence of combinations of digitonin with selected phenolics, terpenoids, and alkaloids on the expression and activity of P-glycoprotein in leukaemia and colon cancer cells","volume":"21","author":"Eid","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1021\/np50113a007","article-title":"Indole alkaloids from peschiera laeta that enhance vinblastine-mediated cytotoxicity with multidrug-resistant cells","volume":"57","author":"You","year":"1994","journal-title":"J. Nat. Prod."},{"key":"ref_98","first-page":"1505","article-title":"Voacamine, a bisindolic alkaloid from peschiera fuchsiaefolia, enhances the cytotoxic effect of doxorubicin on multidrug-resistant tumor cells","volume":"23","author":"Meschini","year":"2003","journal-title":"Int. J. Oncol."},{"key":"ref_99","first-page":"1597","article-title":"Voacamine, an alkaloid extracted from peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells","volume":"27","author":"Meschini","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/BF02977779","article-title":"Isolation of limonoids and alkaloids from Phellodendron amurense and their multidrug resistance (MDR) reversal activity","volume":"30","author":"Min","year":"2007","journal-title":"Arch. Pharm. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.taap.2008.02.026","article-title":"In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression","volume":"230","author":"Han","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1093\/jac\/dkq186","article-title":"Piperine as an inhibitor of rv1258c, a putative multidrug efflux pump of mycobacterium tuberculosis","volume":"65","author":"Sharma","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1093\/jac\/dkl460","article-title":"Bacterial efflux pump inhibitors from natural sources","volume":"59","author":"Stavri","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.phymed.2015.01.002","article-title":"Cytotoxicity of the indole alkaloid reserpine from Rauwolfia serpentina against drug-resistant tumor cells","volume":"22","author":"Abdelfatah","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/0006-2952(95)00115-G","article-title":"Novel dithiane analogues of tiapamil with high activity to overcome multidrug resistance in vitro","volume":"50","author":"Eliason","year":"1995","journal-title":"Biochem. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/(SICI)1099-1573(200003)14:2<139::AID-PTR608>3.0.CO;2-8","article-title":"The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet (k) determinant","volume":"14","author":"Gibbons","year":"2000","journal-title":"Phytother. Res."},{"key":"ref_107","first-page":"2737","article-title":"Antitumour properties of acridone alkaloids on a murine lymphoma cell line","volume":"28","author":"Rethy","year":"2008","journal-title":"Anticancer Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/S0006-2952(02)00902-4","article-title":"The alkaloid sanguinarine is effective against multidrug resistance in human cervical cells via bimodal cell death","volume":"63","author":"Ding","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.etp.2006.01.008","article-title":"Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells","volume":"58","author":"Weerasinghe","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/BF02968246","article-title":"Aporphine alkaloids and their reversal activity of multidrug resistance (MDR) from the stems and rhizomes of sinomenium acutum","volume":"29","author":"Min","year":"2006","journal-title":"Arch. Pharm. Res."},{"key":"ref_111","first-page":"1189","article-title":"Inhibitory effect of steroidal alkaloids on drug transport and multidrug resistance in human cancer cells","volume":"21","author":"Lavie","year":"2001","journal-title":"Anticancer Res."},{"key":"ref_112","first-page":"256","article-title":"Reversal of adriamycin resistance by matrine in leukemia multidrug resistance cell line k562\/adm","volume":"26","author":"Ding","year":"2004","journal-title":"J. Dalian Med. Univ."},{"key":"ref_113","first-page":"1233","article-title":"Cellular biological effects of matrine on k562 and k562\/vin cells","volume":"18","author":"Li","year":"2001","journal-title":"Chin. J. Pathophysiol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.phymed.2010.07.014","article-title":"Stemona alkaloids, from traditional Thai medicine, increase chemosensitivity via P-glycoprotein-mediated multidrug resistance","volume":"18","author":"Chanmahasathien","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1349-7006.2005.00057.x","article-title":"Cepharanthine potently enhances the sensitivity of anticancer agents in k562 cells","volume":"96","author":"Ikeda","year":"2005","journal-title":"Cancer Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.phymed.2014.04.029","article-title":"Tetrandrine and fangchinoline, bisbenzylisoquinoline alkaloids from stephania tetrandra can reverse multidrug resistance by inhibiting P-glycoprotein activity in multidrug resistant human cancer cells","volume":"21","author":"Sun","year":"2014","journal-title":"Phytomedicine"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1979","DOI":"10.1248\/bpb.28.1979","article-title":"Reversal of P-glycoprotein-dependent resistance to vinblastine by newly synthesized bisbenzylisoquinoline alkaloids in mouse leukemia p388 cells","volume":"28","author":"Wang","year":"2005","journal-title":"Biol. Pharm. Bull."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00001813-199803000-00008","article-title":"The bis benzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein","volume":"9","author":"Choi","year":"1998","journal-title":"Anticancer Drugs"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1016\/j.bmcl.2004.06.074","article-title":"Cytotoxic effects and reversal of multidrug resistance by ibogan and related indole alkaloids","volume":"14","author":"Kam","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1017\/S1461145709990848","article-title":"Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2)","volume":"13","author":"Tournier","year":"2010","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/jac\/dkq079","article-title":"Natural and synthetic compounds such as trimethoprim behave as inhibitors of efflux in gram-negative bacteria","volume":"65","author":"Piddock","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.fitote.2011.01.015","article-title":"Alkaloids derived from genus Veratrum and Peganum of mongolian origin as multidrug resistance inhibitors of cancer cells","volume":"82","author":"Ivanova","year":"2011","journal-title":"Fitoterapia"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.phymed.2015.02.003","article-title":"Enhancing activity of antibiotics against staphylococcus aureus: Zanthoxylum capense constituents and derivatives","volume":"22","author":"Cabral","year":"2015","journal-title":"Phytomedicine"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ptr.1112","article-title":"Activity of Zanthoxylum clava-herculis extracts against multi-drug resistant methicillin-resistant Staphylococcus aureus (MDR-MRSA)","volume":"17","author":"Gibbons","year":"2003","journal-title":"Phytother. Res."},{"key":"ref_125","first-page":"367","article-title":"In vitro search for synergy between flavonoids and epirubicin on multidrug-resistant cancer cells","volume":"19","author":"Gyemant","year":"2005","journal-title":"In Vivo"},{"key":"ref_126","first-page":"761","article-title":"Reversal effect and its mechanism of ampelopsin on multidrug resistance in K562\/ADR cells","volume":"34","author":"Ye","year":"2009","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Fiamegos, Y.C., Kastritis, P.L., Exarchou, V., Han, H., Bonvin, A.M., Vervoort, J., Lewis, K., Hamblin, M.R., and Tegos, G.P. (2011). Antimicrobial and efflux pump inhibitory activity of caffeoylquinic acids from Artemisia absinthium against gram-positive pathogenic bacteria. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0018127"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1055\/s-2002-36347","article-title":"Two flavonols from Artemisa annua which potentiate the activity of berberine and norfloxacin against a resistant strain of Staphylococcus aureus","volume":"68","author":"Stermitz","year":"2002","journal-title":"Planta Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1007\/BF00236389","article-title":"Antimalarial activity of Artemisia annua flavonoids from whole plants and cell cultures","volume":"11","author":"Liu","year":"1992","journal-title":"Plant Cell Rep."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0167-4889(01)00175-6","article-title":"Inhibition of the multidrug resistance P-glycoprotein activity by green tea polyphenols","volume":"1542","author":"Jodoin","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Knop, J., Misaka, S., Singer, K., Hoier, E., M\u00fcller, F., Glaeser, H., K\u00f6nig, J., and Fromm, M.F. (2015). Inhibitory effects of green tea and (\u2013)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139370"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1002\/ptr.1420","article-title":"Antimycobacterial constituents from Juniperus procera, Ferula communis and Plumbago zeylanica and their in vitro synergistic activity with isonicotinic acid hydrazide","volume":"18","author":"Mossa","year":"2004","journal-title":"Phytother. Res."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0009-2797(98)00092-1","article-title":"The effect of the flavonoids, quercetin, myricetin and epicatechin on the growth and enzyme activities of MCF7 human breast cancer cells","volume":"116","author":"Rodgers","year":"1998","journal-title":"Chem. Biol. Interact."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ejps.2005.03.001","article-title":"Modulation of drug transport by selected flavonoids: Involvement of P-gp and OCT?","volume":"25","author":"Ofer","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.bbrc.2004.03.040","article-title":"Interaction of the breast cancer resistance protein with plant polyphenols","volume":"317","author":"Cooray","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.bcp.2004.11.002","article-title":"Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2","volume":"69","author":"Wortelboer","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1124\/jpet.102.044412","article-title":"Effects of the flavonoids biochanin a, morin, phloretin, and silymarin on P-glycoprotein-mediated transport","volume":"304","author":"Zhang","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1124\/mol.65.5.1208","article-title":"Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport","volume":"65","author":"Zhang","year":"2004","journal-title":"Mol. Pharmacol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1093\/jac\/dkn178","article-title":"Plant phenolic compounds as ethidium bromide efflux inhibitors in Mycobacterium smegmatis","volume":"62","author":"Lechner","year":"2008","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1021\/jf063138v","article-title":"Polymethoxylated flavones and other phenolic derivates from citrus in their inhibitory effects on P-glycoprotein-mediated transport of talinolol in Caco-2 cells","volume":"55","author":"Manthey","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0006-291X(02)00755-6","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance by 5,6,7,3\u2032,4\u2032-pentamethoxyflavone (sinensetin)","volume":"295","author":"Choi","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.lfs.2004.06.015","article-title":"Effects of grapefruit juice on the multidrug transporter P-glycoprotein in the human proximal tubular cell line hk-2","volume":"76","author":"Romiti","year":"2004","journal-title":"Life Sci."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3109\/03639045.2013.819885","article-title":"Enhanced oral bioavailability of felodipine by naringenin in wistar rats and inhibition of P-glycoprotein in everted rat gut sacs in vitro","volume":"40","author":"Sridhar","year":"2014","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_144","first-page":"45","article-title":"Screening of flavonoids for their potential inhibitory effect on P-glycoprotein activity in human cervical carcinoma kb cells","volume":"43","author":"Khantamat","year":"2004","journal-title":"Chiang Mai Med. Bull."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1002\/jps.20975","article-title":"Grapefruit juice\u2013Drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells","volume":"96","author":"Derendorf","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1021\/jf0728451","article-title":"Effect of grapefruit juice, naringin, naringenin, and bergamottin on the intestinal carrier-mediated transport of talinolol in rats","volume":"56","author":"Derendorf","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0014-2999(00)00180-1","article-title":"Effect of bioflavonoids on vincristine transport across blood\u2013brain barrier","volume":"395","author":"Mitsunaga","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ejphar.2009.09.040","article-title":"Inhibition of P-glycoprotein activity by limonin and other secondary metabolites from citrus species in human colon and leukaemia cell lines","volume":"626","author":"Hamdan","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/ptr.2951","article-title":"Modulation of P-glycoprotein atpase activity by some phytoconstituents","volume":"24","author":"Najar","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1080\/14786419.2014.994210","article-title":"Curcuma ecalcarata\u2013New natural source of pinocembrin and piperitenone","volume":"29","author":"Rameshkumar","year":"2015","journal-title":"Nat. Prod. Res."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1080\/10286020.2011.620393","article-title":"Uptake characteristics of pinocembrin and its effect on P-glycoprotein at the blood\u2013brain barrier in in vitro cell experiments","volume":"14","author":"Yang","year":"2012","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Limtrakul, P., Anuchapreeda, S., and Buddhasukh, D. (2004). Modulation of human multidrug-resistance MDR-1 gene by natural curcuminoids. BMC Cancer, 4.","DOI":"10.1186\/1471-2407-4-13"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s11010-011-1064-2","article-title":"The short-time treatment with curcumin sufficiently decreases cell viability, induces apoptosis and copper enhances these effects in multidrug-resistant k562\/a02 cells","volume":"360","author":"Lu","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1021\/np058057s","article-title":"Metabolites of the \u201csmoke tree\u201d, Dalea spinosa, potentiate antibiotic activity against multidrug-resistant Staphylococcus aureus","volume":"69","author":"Belofsky","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1128\/AAC.01533-09","article-title":"Efflux pumps are involved in the defense of gram-negative bacteria against the natural products isobavachalcone and diospyrone","volume":"54","author":"Kuete","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_156","unstructured":"Lechner, D., Gibbons, S., Jachak, S., Srivastava, A., and Bucar, F. (2008, January 3\u20138). In Curcuminoids as Efflux Pump Inhibitors (EPIS) in Mycobacterium Smegmatis mc2155. Proceedings of the 7th Joint Meeting of GA, AFERP, ASP, PSI & SIF, Athens, Greece."},{"key":"ref_157","first-page":"93","article-title":"Cytosolic superoxide dismutase activity after photodynamic therapy, intracellular distribution of photofrin ii and hypericin, and P-glycoprotein localization in human colon adenocarcinoma","volume":"45","author":"Saczko","year":"2007","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1046\/j.1365-2125.1999.00052.x","article-title":"Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the hiv-1 protease inhibitor saquinavir by grapefruit juice components","volume":"48","author":"Eagling","year":"1999","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.3892\/mmr.2013.1742","article-title":"Icaritin reverses multidrug resistance of HepG2\/ADR human hepatoma cells via downregulation of mdr1 and p\u2011glycoprotein expression","volume":"8","author":"Sun","year":"2013","journal-title":"Mol. Med. Rep."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1002\/ptr.2695","article-title":"Modulation of drug resistance in staphylococcus aureus by a kaempferol glycoside from Herissantia tiubae (Malvaceae)","volume":"23","author":"Silva","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_161","first-page":"1","article-title":"Bioactive flavonoids as ABC transporters inhibitors for reversion of multidrug resistance in cancer","volume":"4","author":"Yarla","year":"2013","journal-title":"J. Mar. Sci. Res. Dev."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ejphar.2010.06.069","article-title":"8-prenylnaringenin is an inhibitor of multidrug resistance-associated transporters, P-glycoprotein and MRP1","volume":"644","author":"Krawczenko","year":"2010","journal-title":"Eur. J. Pharmacol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1007\/s11095-011-0368-y","article-title":"5,7-dimethoxyflavone and multiple flavonoids in combination alter the ABCG2-mediated tissue distribution of mitoxantrone in mice","volume":"28","author":"An","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.bbagen.2016.04.007","article-title":"Rhamnetin induces sensitization of hepatocellular carcinoma cells to a small molecular kinase inhibitor or chemotherapeutic agents","volume":"1860","author":"Jia","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Gen. Subj."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1111\/j.1365-2672.2007.03617.x","article-title":"Plagiochin E, a botanic-derived phenolic compound, reverses fungal resistance to fluconazole relating to the efflux pump","volume":"104","author":"Guo","year":"2008","journal-title":"J. Appl. Microbiol."},{"key":"ref_166","first-page":"28","article-title":"Isolation, characterization and quantification of isoflavone in Momordica dioica roxb. Ex wild (cucurbitaceae) fruits","volume":"5","author":"Kale","year":"2012","journal-title":"Int. J. Appl. Res. Nat. Prod."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s12272-011-0217-x","article-title":"Effects of myricetin on the bioavailability of doxorubicin for oral drug delivery in rats: Possible role of CYP3A4 and P-glycoprotein inhibition by myricetin","volume":"34","author":"Choi","year":"2011","journal-title":"Arch. Pharm. Res."},{"key":"ref_168","first-page":"199","article-title":"Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids","volume":"14","author":"Hendrich","year":"2009","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_169","first-page":"1927","article-title":"Seaweed as a new source of flavone, scutellarein 4\u2032-methyl-ether","volume":"41","author":"Sabina","year":"2009","journal-title":"Pak. J. Bot."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"5748","DOI":"10.3390\/molecules19055748","article-title":"In vitro inhibitory effects of scutellarin on six human\/rat cytochrome p450 enzymes and P-glycoprotein","volume":"19","author":"Han","year":"2014","journal-title":"Molecules"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1002\/ptr.2781","article-title":"Inhibition of P-glycoprotein function by procyanidine on blood\u2013brain barrier","volume":"23","author":"He","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Zhao, B.-X., Sun, Y.-B., Wang, S.-Q., Duan, L., Huo, Q.-L., Ren, F., and Li, G.-F. (2013). Grape seed procyanidin reversal of P-glycoprotein associated multi-drug resistance via down-regulation of NF-\u03baB and MAPK\/ERK mediated YB-1 activity in a2780\/t cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071071"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4346","DOI":"10.1158\/0008-5472.CAN-04-0078","article-title":"Phytoestrogens\/flavonoids reverse breast cancer resistance protein\/ABCG2-mediated multidrug resistance","volume":"64","author":"Imai","year":"2004","journal-title":"Cancer Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1111\/j.1745-7254.2008.00884.x","article-title":"Intra-herb pharmacokinetics interaction between quercetin and isorhamentin1","volume":"29","author":"Lan","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/cbdv.200790001","article-title":"P-glycoprotein inhibitory activity of two phenolic compounds, (\u2212)-syringaresinol and tricin from Sasa borealis","volume":"4","author":"Jeong","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s00280-010-1396-8","article-title":"Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects","volume":"67","author":"Enomoto","year":"2011","journal-title":"J. Cancer Chemother. Pharmacol."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s12272-011-1117-9","article-title":"Effects of baicalein on the pharmacokinetics of tamoxifen and its main metabolite, 4-hydroxytamoxifen, in rats: Possible role of cytochrome P450 3A4 and P-glycoprotein inhibition by baicalein","volume":"34","author":"Li","year":"2011","journal-title":"Arch. Pharm. Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1002\/jps.10283","article-title":"Effect of flavonoids on MRP1-mediated transport in panc-1 cells","volume":"92","author":"Nguyen","year":"2003","journal-title":"J. Pharm. Sci."},{"key":"ref_179","first-page":"3512","article-title":"Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis","volume":"8","author":"Tyagi","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_180","first-page":"191","article-title":"Inhibition of P-glycoprotein at the blood\u2013brain barrier by phytochemicals derived from traditional chinese medicine","volume":"7","author":"Mahringer","year":"2010","journal-title":"Cancer Genom. Proteom."},{"key":"ref_181","first-page":"49","article-title":"Effect of resveratrol on the pharmacokinetics of oral and intravenous nicardipine in rats: Possible role of P-glycoprotein inhibition by resveratrol","volume":"64","author":"Choi","year":"2009","journal-title":"Die Pharm. Int. J. Pharm. Sci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.bbrc.2004.12.081","article-title":"Effects of dietary chemopreventive phytochemicals on P-glycoprotein function","volume":"327","author":"Nabekura","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.biopha.2008.07.089","article-title":"Reversal effect of resveratrol on multidrug resistance in kbv200 cell line","volume":"62","author":"Quan","year":"2008","journal-title":"Biomed. Pharmacother."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.pharep.2015.08.018","article-title":"Effect of resveratrol on the pharmacokinetics of fexofenadine in rats: Involvement of P-glycoprotein inhibition","volume":"68","author":"Bedada","year":"2016","journal-title":"Pharmacol. Rep."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"7355","DOI":"10.1016\/j.bmc.2007.07.020","article-title":"Natural triterpenoids from Cecropia lyratiloba are cytotoxic to both sensitive and multidrug resistant leukemia cell lines","volume":"15","author":"Simoes","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1021\/np050554l","article-title":"Aegicerin, the first oleanane triterpene with wide-ranging antimycobacterial activity, isolated from Clavija procera","volume":"69","author":"Rojas","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/j.bcp.2005.04.001","article-title":"Inhibition of multidrug resistance proteins MRP1 and MRP2 by a series of \u03b1,\u03b2-unsaturated carbonyl compounds","volume":"69","author":"Wortelboer","year":"2005","journal-title":"Biochem. Pharmacol."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s11101-009-9126-8","article-title":"Jatrophane diterpenes from euphorbia spp. As modulators of multidrug resistance in cancer therapy","volume":"8","author":"Corea","year":"2009","journal-title":"Phytochem. Rev."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1021\/jm301441w","article-title":"Enhancing macrocyclic diterpenes as multidrug-resistance reversers: Structure\u2013Activity studies on jolkinol D derivatives","volume":"56","author":"Reis","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.bmc.2006.09.028","article-title":"Apoptosis induction and modulation of P-glycoprotein mediated multidrug resistance by new macrocyclic lathyrane-type diterpenoids","volume":"15","author":"Duarte","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1021\/np3004003","article-title":"Jatrophane diterpenes from Euphorbia mellifera and their activity as P-glycoprotein modulators on multidrug-resistant mouse lymphoma and human colon adenocarcinoma cells","volume":"75","author":"Valente","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2174\/138161206775201893","article-title":"Inhibition of multidrug resistance of cancer cells by natural diterpenes, triterpenes and carotenoids","volume":"12","author":"Tanaka","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1021\/np060046r","article-title":"Euphoportlandols a and b, tetracylic diterpene polyesters from euphorbia portlandica and their anti-mdr effects in cancer cells","volume":"69","author":"Madureira","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_194","first-page":"3259","article-title":"Inhibition of P-glycoprotein transport activity in a resistant mouse lymphoma cell line by diterpenic lactones","volume":"25","author":"Ferreira","year":"2005","journal-title":"Anticancer Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"9323","DOI":"10.1016\/j.bmc.2008.08.071","article-title":"Synergistic interaction between P-glycoprotein modulators and epirubicine on resistant cancer cells","volume":"16","author":"Duarte","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.taap.2013.12.015","article-title":"Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb\u2013drug interactions mediated via P-gp","volume":"275","author":"Li","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0304-3835(02)00593-1","article-title":"Pentacyclic triterpenes from Chrysobalanaceae sp.: Cytotoxicity on multidrug resistant and sensitive leukemia cell lines","volume":"190","author":"Fernandes","year":"2003","journal-title":"Cancer Lett."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/ajoc.201600462","article-title":"Dihydro-\u03b2-agarofurans from the australian endemic rainforest plant Denhamia pittosporoides inhibit leucine transport in prostate cancer cells","volume":"5","author":"Wibowo","year":"2016","journal-title":"Asian J. Org. Chem."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1039\/b915678j","article-title":"Novel dihydro-\u03b2-agarofuran sesquiterpenes as potent modulators of human P-glycoprotein dependent multidrug resistance","volume":"7","author":"Castanys","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1021\/jm0309699","article-title":"Sar studies of dihydro-\u03b2-agarofuran sesquiterpenes as inhibitors of the multidrug-resistance phenotype in a Leishmania tropica line overexpressing a P-glycoprotein-like transporter","volume":"47","author":"Campillo","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1016\/j.tiv.2011.09.023","article-title":"Inhibitory effects of limonin on six human cytochrome P450 enzymes and P-glycoprotein in vitro","volume":"25","author":"Han","year":"2011","journal-title":"Toxicol. In Vitro"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1002\/ptr.1711","article-title":"Isopimaric acid from pinus nigra shows activity against multidrug-resistant and emrsa strains of Staphylococcus aureus","volume":"19","author":"Smith","year":"2005","journal-title":"Phytother. Res."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1128\/AAC.00216-07","article-title":"The phenolic diterpene totarol inhibits multidrug efflux pump activity in Staphylococcus aureus","volume":"51","author":"Smith","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1016\/j.bmc.2011.03.055","article-title":"New 29-nor-cycloartanes with a 3,4-seco-and a novel 2,3-seco-structure from the leaves of Sinocalycanthus chinensis","volume":"19","author":"Kashiwada","year":"2011","journal-title":"Bioorg. Med. Chem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1021\/np900091y","article-title":"Sipholane triterpenoids: Chemistry, reversal of ABCB1\/P-glycoprotein-mediated multidrug resistance, and pharmacophore modeling","volume":"72","author":"Jain","year":"2009","journal-title":"J. Nat. Prod."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1021\/np0605889","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance by sipholane triterpenoids","volume":"70","author":"Jain","year":"2007","journal-title":"J. Nat. Prod."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1111\/j.2042-7158.2012.01549.x","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance of human hepatic cancer cells by astragaloside II","volume":"64","author":"Huang","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.fitote.2008.09.010","article-title":"Selective modulation of P-glycoprotein activity by steroidal saponines from Paris polyphylla","volume":"80","author":"Nguyen","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"178","DOI":"10.3389\/fphar.2014.00178","article-title":"Evaluation of drug interaction potential of Labisia pumila (kacip fatimah) and its constituents","volume":"5","author":"Manda","year":"2014","journal-title":"Front. Pharmacol."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1021\/np070458f","article-title":"Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance in HepG2\/dox cells","volume":"71","author":"Hu","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ijantimicag.2010.09.011","article-title":"Inhibition of efflux pumps in Methicillin-resistant Staphylococcus aureus and Enterococcus faecalis resistant strains by triterpenoids from Momordica balsamina","volume":"37","author":"Ramalhete","year":"2011","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"6942","DOI":"10.1016\/j.bmc.2009.08.020","article-title":"New potent P-glycoprotein modulators with the cucurbitane scaffold and their synergistic interaction with doxorubicin on resistant cancer cells","volume":"17","author":"Ramalhete","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1055\/s-2003-38483","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng","volume":"69","author":"Choi","year":"2003","journal-title":"Planta Med."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"8881","DOI":"10.1158\/0008-5472.CAN-08-2037","article-title":"The taccalonolides: Microtubule stabilizers that circumvent clinically relevant taxane resistance mechanisms","volume":"68","author":"Risinger","year":"2008","journal-title":"Cancer Res."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"6303","DOI":"10.1016\/S0040-4039(98)01336-7","article-title":"Agosterol A, a novel polyhydroxylated sterol acetate reversing multidrug resistance from a marine sponge of Spongia sp.","volume":"39","author":"Aoki","year":"1998","journal-title":"Tetrahedron Lett."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"184","DOI":"10.2174\/1573406411006040184","article-title":"Phytosterols in physiological concentrations target multidrug resistant cancer cells","volume":"6","author":"Rubis","year":"2010","journal-title":"Med. Chem."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3109\/00498254.2011.587551","article-title":"Pharmacokinetic characterization of decursinol derived from Angelica gigas Nakai in rats","volume":"41","author":"Song","year":"2011","journal-title":"Xenobiotica"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/ijc.20505","article-title":"Inhibition of leukemic cell growth by a novel anti-cancer drug (GUT-70) from Calophyllum brasiliense that acts by induction of apoptosis","volume":"113","author":"Kimura","year":"2005","journal-title":"Int. J. Cancer"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/sj.bjp.0703433","article-title":"Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by caco-2 cells and on the activity of cytochrome p450 3a4","volume":"130","author":"Ohnishi","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1211\/002235702603","article-title":"The effect of food components on the absorption of P-gp substrates: A review","volume":"55","author":"Deferme","year":"2003","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.fitote.2015.03.025","article-title":"Reversal of P-glycoprotein-mediated multidrug resistance in MCF-7\/ADR cancer cells by sesquiterpene coumarins","volume":"103","author":"Kasaian","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1055\/s-0030-1270987","article-title":"Farnesiferol A from Ferula persica and galbanic acid from Ferula szowitsiana inhibit P-glycoprotein-mediated rhodamine efflux in breast cancer cell lines","volume":"77","author":"Iranshahi","year":"2011","journal-title":"Planta Med."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1055\/s-2006-931574","article-title":"Conferone from Ferula schtschurowskiana enhances vinblastine cytotoxicity in MDCK-MDR1 cells by competitively inhibiting P-glycoprotein transport","volume":"72","author":"Barthomeuf","year":"2006","journal-title":"Planta Med."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1590\/S1517-83822010000300006","article-title":"Effect of galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana, as an inhibitor of efflux mechanism in resistant clinical isolates of staphylococcus aureus","volume":"41","author":"Bazzaz","year":"2010","journal-title":"Braz. J. Microbiol."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"343808","DOI":"10.1155\/2013\/343808","article-title":"Biological activities and pharmacokinetics of praeruptorins from Peucedanum species: A systematic review","volume":"2013","author":"Sarkhail","year":"2013","journal-title":"BioMed. Res. Int."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/s00280-004-0914-y","article-title":"Inhibition of P-glycoprotein transport function and reversion of MDR1 multidrug resistance by cnidiadin","volume":"56","author":"Barthomeuf","year":"2005","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1124\/mol.52.4.613","article-title":"The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells","volume":"52","author":"Kowalski","year":"1997","journal-title":"Mol. Pharmacol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"7053","DOI":"10.1016\/j.tet.2003.07.020","article-title":"Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp.","volume":"60","author":"Aoki","year":"2004","journal-title":"Tetrahedron"},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"7219","DOI":"10.1021\/jo00103a011","article-title":"Hapalosin, a cyanobacterial cyclic depsipeptide with multidrug-resistance reversing activity","volume":"59","author":"Stratmann","year":"1994","journal-title":"J. Org. Chem."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"2770","DOI":"10.1021\/ol200904v","article-title":"Nocardioazines: A novel bridged diketopiperazine scaffold from a marine-derived bacterium inhibits P-glycoprotein","volume":"13","author":"Raju","year":"2011","journal-title":"Org. Lett."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1742-7843.2012.00921.x","article-title":"Gambogic acid as a non-competitive inhibitor of ATP-binding cassette transporter B1 reverses the multidrug resistance of human epithelial cancers by promoting ATP-binding cassette transporter B1 protein degradation","volume":"112","author":"Wang","year":"2013","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/np050227d","article-title":"Polyacylated oligosaccharides from medicinal Mexican morning glory species as antibacterials and inhibitors of multidrug resistance in Staphylococcus aureus","volume":"69","author":"Kaatz","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"34","DOI":"10.2174\/1874285801307010034","article-title":"Microbial efflux systems and inhibitors: Approaches to drug discovery and the challenge of clinical implementation","volume":"7","author":"Kourtesi","year":"2013","journal-title":"Open Microbiol. J."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Su, J., Lai, H., Chen, J., Li, L., Wong, Y.-S., Chen, T., and Li, X. (2013). Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063502"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/S0960-894X(03)00294-4","article-title":"Multidrug resistance reversal activity of key ningalin analogues","volume":"13","author":"Soenen","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S0924-8579(03)00085-2","article-title":"Berberis aetnensis C. Presl. extracts: Antimicrobial properties and interaction with ciprofloxacin","volume":"22","author":"Musumeci","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S0006-2952(98)00107-5","article-title":"Pkc-independent modulation of multidrug resistance in cells with mutant (v185) but not wild-type (g185) P-glycoprotein by bryostatin 1","volume":"56","author":"Spitaler","year":"1998","journal-title":"Biochem. Pharmacol."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1124\/jpet.105.098541","article-title":"Characterization of P-glycoprotein inhibition by major cannabinoids from marijuana","volume":"317","author":"Zhu","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"e153","DOI":"10.7717\/peerj.153","article-title":"Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines","volume":"1","author":"Feinshtein","year":"2013","journal-title":"Peer J."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"27576","DOI":"10.3390\/ijms161126051","article-title":"Borneol Depresses P-Glycoprotein Function by a NF-\u03baB Signaling Mediated Mechanism in a Blood Brain Barrier In Vitro Model","volume":"16","author":"Fan","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1055\/s-0032-1327896","article-title":"Phytochemical analysis and cytotoxicity towards multidrug-resistant leukemia cells of essential oils derived from lebanese medicinal plants","volume":"78","author":"Saab","year":"2012","journal-title":"Planta Med."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0960-894X(03)00316-0","article-title":"Polyacylated neohesperidosides from Geranium caespitosum: Bacterial multidrug resistance pump inhibitors","volume":"13","author":"Stermitz","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/S0966-842X(01)02175-8","article-title":"The emergence and evolution of methicillin-resistant Staphylococcus aureus","volume":"9","author":"Hiramatsu","year":"2001","journal-title":"Trends Microbiol."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.antiviral.2016.01.001","article-title":"Characterization of the inhibitory effect of an extract of Prunella vulgaris on ebola virus glycoprotein (gp)-mediated virus entry and infection","volume":"127","author":"Zhang","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1016\/j.bcp.2006.06.036","article-title":"Gomisin A alters substrate interaction and reverses P-glycoprotein-mediated multidrug resistance in HepG2-DR cells","volume":"72","author":"Wan","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1002\/ptr.2650","article-title":"Potent modulation of P-glycoprotein activity by naturally occurring phenylbutenoids from Zingiber cassumunar","volume":"23","author":"Chung","year":"2009","journal-title":"Phytother. Res."},{"key":"ref_247","doi-asserted-by":"crossref","unstructured":"Dewick, P.M. (2002). Medicinal Natural Products: A Biosynthetic Approach, John Wiley & Sons.","DOI":"10.1002\/0470846275"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1073\/pnas.86.2.695","article-title":"Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites","volume":"86","author":"Casals","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0166-6851(93)90252-S","article-title":"Amplification of pfmdr1 associated with mefloquine and halofantrine resistance in Plasmodium falciparum from thailand","volume":"57","author":"Wilson","year":"1993","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0378-1119(95)00533-C","article-title":"Increase in mRNA of multiple EH P-gp genes encoding P-glycoprotein homologues in emetine-resistant Entamoeba histolytica parasites","volume":"164","author":"Descoteaux","year":"1995","journal-title":"Gene"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1016\/0006-2952(94)90067-1","article-title":"P-glycoprotein overexpression in methotrexate-resistant Leishmania tropica","volume":"47","author":"Gamarro","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.bmc.2013.12.022","article-title":"Synthesis and evaluation of strychnos alkaloids as MDR reversal agents for cancer cell eradication","volume":"22","author":"Munagala","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_253","first-page":"52","article-title":"Irinotecan treatment in cancer patients with ugt1a1 polymorphisms","volume":"17","author":"Innocenti","year":"2003","journal-title":"Oncology"},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"Okyar, A., Piccolo, E., Ahowesso, C., Filipski, E., Hossard, V., Guettier, C., La Sorda, R., Tinari, N., Iacobelli, S., and L\u00e9vi, F. (2011). Strain-and sex-dependent circadian changes in ABCC2 transporter expression: Implications for irinotecan chronotolerance in mouse ileum. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020393"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1124\/dmd.31.9.1151","article-title":"Application of compartmental modeling to an examination of in vitro intestinal permeability data: Assessing the impact of tissue uptake, P-glycoprotein, and CYP3A","volume":"31","author":"Johnson","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"ref_256","first-page":"2849","article-title":"Increased penetration of paclitaxel into the brain by inhibition of P-glycoprotein","volume":"9","author":"Kemper","year":"2003","journal-title":"Clin. Cancer Res."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.taap.2013.12.018","article-title":"Optimization of irinotecan chronotherapy with P-glycoprotein inhibition","volume":"274","author":"Filipski","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1128\/AAC.47.3.1047-1051.2003","article-title":"Influence of P-glycoprotein inhibitors on accumulation of macrolides in J774 murine macrophages","volume":"47","author":"Seral","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"867","DOI":"10.3109\/14756366.2016.1149476","article-title":"Advances in plant-based inhibitors of Pglycoprotein","volume":"31","author":"Yu","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_260","first-page":"5977","article-title":"Flavonol stimulated efflux of 7,12-dimethylbenz(a)-anthracene in multidrug-resistant breast cancer cells","volume":"53","author":"Phang","year":"1993","journal-title":"Cancer Res."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/0006-2952(94)90568-1","article-title":"Modulation of Adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells: Activation of Pglycoprotein as a putative mechanism","volume":"48","author":"Critchfield","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_262","first-page":"3","article-title":"Secondary metabolites from plants inhibiting ABC transporters and reversing resistance of cancer cells and microbes to cytotoxic and antimicrobial agents","volume":"23","author":"Wink","year":"2012","journal-title":"Front. Microbiol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/6\/871\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:36:58Z","timestamp":1760207818000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/6\/871"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,25]]},"references-count":262,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["molecules22060871"],"URL":"https:\/\/doi.org\/10.3390\/molecules22060871","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,25]]}}}