The clinical applications of some well-known chemotherapeutic drugs for cancer treatment have been restricted nowadays owing to their adverse effects on many physiological systems. In this experimental study, maslinic acid (MA) isolated from Olea europaea (Olive) fruit extract was used to mitigate the cytotoxicity induced by Doxorubicin (DOX) in human healthy peripheral blood mononuclear cells (hPBMCs). Self-assembled maslinic acid (SA-MA) was obtained in ethanol-water mixture (35.5 mM: 4:1 v/v). The morphology of SA-MA was analyzed by various physicochemical characterization techniques, which revealed its micro-metric vesicular architecture as well as nano-vesicular appearances. In this study, treatment of hPBMCs with DOX has been found to generate severe intracellular oxidative stress, which was significantly mitigated after pre-treatment with SA-MA. Alteration of hPBMC morphologies after DOX treatment was also restored notably by pre-treatment with SA-MA. Furthermore, pentoxifylline (TNF-α inhibitor) and indomethacin (COX-2 inhibitor) were used to investigate the responsible pathway by which SA-MA protected hPBMCs from DOX-induced cellular stress. Restoration of hPBMC viability above 92% in both cases confirmed that SA-MA protected the cells by inhibiting inflammatory pathways generated by DOX treatment. Subsequently, in molecular docking study, it was also evaluated that MA could successfully bind with the pocket region of Keap1, while Nrf2 was capable of upregulating cytoprotecting genes.

目前一些著名的癌症化疗药物由于对许多生理系统的不良影响而限制了其临床应用。在这项实验研究中，使用从油橄榄（ Olea europaea）果实提取物中分离出的山楂酸（MA）来减轻阿霉素（DOX）对人类健康外周血单核细胞（hPBMC）引起的细胞毒性。自组装山楂酸 (SA-MA) 在乙醇-水混合物 (35.5 mM: 4:1 v/v) 中获得。通过各种物理化学表征技术对 SA-MA 的形态进行了分析，揭示了其微米级囊泡结构以及纳米囊泡外观。在这项研究中，发现用 DOX 处理 hPBMC 会产生严重的细胞内氧化应激，而在用 SA-MA 预处理后，这种氧化应激得到显着减轻。DOX 处理后 hPBMC 形态的改变也通过 SA-MA 预处理得到显着恢复。此外，使用己酮可可碱（TNF-α 抑制剂）和吲哚美辛（COX-2 抑制剂）来研究 SA-MA 保护 hPBMC 免受 DOX 诱导的细胞应激的作用途径。两种情况下 hPBMC 活力恢复超过 92%，证实 SA-MA 通过抑制 DOX 治疗产生的炎症途径来保护细胞。随后，在分子对接研究中，还评估MA能够成功与Keap1的口袋区域结合，而Nrf2能够上调细胞保护基因。