Abstract Objective: Lung cancer (LC) is well known for its high morbidity and mortality rates. The primary objective of this study was to investigate the synergistic effects of hesperetin (HES), a bioactive compound found in sweet oranges, in combination with cisplatin (CDDP), on LC treatment. Methods: Human A549 and mouse Lewis lung cancer (LLC) cell lines were treated with HES, CDDP, or their combination. Cell viability was assessed using CCK-8 assays. Western blotting evaluated Nrf2 pathway modulation. In vivo, LLC xenografts in C57BL/6 mice assessed tumor growth and kidney function. Results: The combination of HES with CDDP synergistically inhibited lung cancer cell viability in A549 and LLC cells compared to individual treatments (P < 0.05). This synergistic effect was associated with reduced Nrf2 pathway activation, enhancing oxidative stress sensitivity induced by CDDP. In vivo, HES + CDDP treatment significantly suppressed tumor growth in LLC xenograft mice, accompanied by alleviated CDDP-induced kidney injury, indicated by improved histopathology, reduced apoptosis, and restored antioxidant enzyme levels in kidney tissues. Conclusions: Combining HES with CDDP enhances LC treatment efficacy by synergistically inhibiting tumor growth and modulating the Nrf2 pathway. Additionally, HES protects against CDDP-induced kidney injury, suggesting potential benefits in LC treatment strategies.

Aims To provide evidence for the clinically rational administration of bupropion (BUP), the effects of high-fat diet and CYP2B6 mutants on BUP and hydroxybupropion (HBUP) among 44 healthy Chinese subjects. Methods The concentrations of BUP and HBUP in plasma were determined with a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. Genotypes were ascertained after amplified by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results The maximum plasma concentration (Cmax) and time to Cmax (tmax) of BUP as well as the concentration–time curve (AUC(0→96)) and Cmax of HBUP all increased by 1.18-, 1.41-, 1.38-, and 1.33-fold in the feeding group relative to the fasting group, respectively. Interestingly, the Cmax and terminal half-life (t1/2) of BUP increased by 1.33- and 1.39-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Similarly, the apparent volume of distribution (Vd) and clearance (CL) of HBUP increased by 1.38- and 1.59-fold, respectively, while the Cmax and AUC(0→96) of HBUP decreased by 1.44- and 1.49-fold among those subjects carrying the CYP2B6*1/*1 genotype in the feeding group relative to those in the fasting group. Concliusion These data suggest that high-fat diet and CYP2B6 mutants can influence the pharmacokinetic parameters of BUP and HBUP, thereby offering clear evidence for the rational administration of BUP among Chinese subjects in clinical settings.