Isolation of Bioactive Compounds from Pistacia integerrima with Promising Effects on Reverse Cancer Multidrug Resistance

Abstract: Pistacia integerrima grows in some areas of Pakistan and some other south Asian countries such as Afghanistan, India, Nepal, and Myanmar. It is an important medicinal plant which has been traditionally used for the treatment of asthma, cough, and dysentery. In the present study, we intend to re-isolate bioactive compounds (I–III) from P. integerrima galls extracts. The chloroform extract was subjected to column chromatography that afforded three reported chemical constituents, 7-methoxynaringenin (I), 7-methoxy-3,5,7,4′-tetrahydroxyflavanone (II), and β-sitosterol (III). Compounds (I–III) were evaluated for multi-drug resistance (MDR) reversing effect by assessing their activity on various genes including transfected mouse gene, human mdrl gene, and transfected mouse T-lymphoma cell lines (L5178 and L5178Y). Compounds (I–III) exhibit significant dose-dependent MDR reversing effect against the T-lymphoma (mouse cell line). in-silico molecular docking investigations performed on compounds (I–III) showed a common binding site for these compounds and Rhodamine 123. Our findings indicated that the relative docking scores correlate satisfactorily with in vitro activities. It could be concluded that the inhibitory activity of compounds (I–III) is largely due to their interactions with the P-glycoprotein (P-gp). The present work could also contribute to the isolation of novel natural compounds that act as potent inhibitors for cancer treatment.