M. KawamiY. YamadaO. IssarachotV. B. JunyaprasertR. YumotoM. TakanoHiroshima UniversityMahidol University2019-08-282019-08-282018-01-01Pharmazie. Vol.73, No.2 (2018), 104-109003171442-s2.0-85041486353https://repository.li.mahidol.ac.th/handle/123456789/47332The extract of Azadirachta indica, commonly known as neem, has found extensive use in traditional medicine for treating various human diseases. In this study, the effect of the 50% ethanol extract of A. indica (AI01) on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) was examined using MDR cell lines, specifically paclitaxel-resistant HepG2 (PR-HepG2) and doxorubicin (DOX)-resistant (DR) colon-26 cells. 96-h treatment of the two cell lines with AI01 (30 μg/mL) showed no effect on the expression of P-gp mRNA (human MDR1 and mouse mdr1b) and protein, while AI01 increased the accumulation of rhodamine 123, a P-gp substrate, in both PR-HepG2 and DR-colon-26 cells. The cytotoxic effects of 48-h treatment with AI01 on the viability of PR-HepG2 and DR-colon-26 cells were not observed. Therefore, 30 μg/mL AI01 may have no cytotoxic and P-gp-inducing effects. Finally, AI01 potentiated the sensitivity of PR-HepG2 and DR-colon-26 cell lines to DOX by 8.6- and 15.3-fold, respectively. These findings suggest that A. indica may be a promising source for a new class of P-gp modulators without cytotoxic/P-gp induction effects.Mahidol UniversityPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1691/ph.2018.7116