Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand.
Department of Biopharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand.
Drug Metab Pharmacokinet. 2023 Jun;50:100500. doi: 10.1016/j.dmpk.2023.100500. Epub 2023 Feb 28.
Black ginger is used as an herbal medicine for self-care and health promotion. Black ginger extract has been shown to alter the function of transporters in several cell types. This study demonstrates the interaction between the extract and 5,7-dimethoxyflavone (DMF) on drug efflux mediated by breast cancer resistance proteins (BCRP) and P-glycoprotein (P-gp) in Caco-2 cells and heterologous cell systems [Madin-Darby canine kidney type II (MDCKII) stably transfected with human BCRP (MDCKII/BCRP) or human P-gp (MDCKII/P-gp)]. The transepithelial flux of H-Digoxin and H-Estrone sulfate, prototypic substrates of P-gp, and BCRP, respectively, across Caco-2 cell monolayers, MDCKII/BCRP, and MDCKII/P-gp cells were determined. The results demonstrate that black ginger extract (10 μg/ml) significantly increases H-Digoxin and H-Estrone sulfate transport from the apical to basolateral side while decreasing transport from the basolateral to apical side of Caco-2 cells and MDCKII cell overexpression of BCRP or P-gp. The effect of the extract on H-Digoxin and H-Estrone sulfate transport was related to a decrease in efflux ratio. Likewise, DMF (5 μM) significantly increased H-Digoxin and H-Estrone sulfate absorption with a decreased efflux ratio compared to the control. Interestingly, the extract also significantly increased absorption of paclitaxel, an anti-cancer drug, which has poor oral absorption. Taken together, co-administration of drugs as substrates of BCRP and P-gp, with the black ginger extract containing DMF, might alter the pharmacokinetic profiles of the medicine.
黑姜被用作自我保健和促进健康的草药。黑姜提取物已被证明可改变几种细胞类型中转运蛋白的功能。本研究表明，在 Caco-2 细胞和异源细胞系统[用人乳腺癌耐药蛋白（BCRP）和 P-糖蛋白（P-gp）稳定转染的 Madin-Darby 犬肾细胞 II 型（MDCKII/BCRP）或人 P-糖蛋白（MDCKII/P-gp）]中，提取物与 5,7-二甲氧基黄酮（DMF）之间存在相互作用，可改变乳腺癌耐药蛋白（BCRP）和 P-糖蛋白（P-gp）介导的药物外排。测定了 H-地高辛和 H-雌酮硫酸盐（分别为 P-gp 和 BCRP 的典型底物）穿过 Caco-2 细胞单层、MDCKII/BCRP 和 MDCKII/P-gp 细胞的跨上皮通量。结果表明，黑姜提取物（10μg/ml）显著增加了 H-地高辛和 H-雌酮硫酸盐从 Caco-2 细胞的顶侧向基底外侧的转运，同时降低了从基底侧向顶侧的转运，以及 MDCKII 细胞过表达 BCRP 或 P-gp。提取物对 H-地高辛和 H-雌酮硫酸盐转运的影响与外排比的降低有关。同样，与对照相比，DMF（5μM）显著增加了 H-地高辛和 H-雌酮硫酸盐的吸收，同时降低了外排比。有趣的是，提取物还显著增加了紫杉醇（一种抗癌药物）的吸收，紫杉醇的口服吸收较差。总之，与含有 DMF 的黑姜提取物共同给药的药物，作为 BCRP 和 P-gp 的底物，可能会改变药物的药代动力学特征。
