Ezuruike Udoamaka F, Chieli Elisabetta, Prieto Jose M
Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, United Kingdom.
Department of Translational Research on New Technologies in Medicine and Surgery, School of Medicine, University of Pisa, Pisa, Italy.
Planta Med. 2019 Aug;85(11-12):987-996. doi: 10.1055/a-0948-9072. Epub 2019 Jul 26.
The rise of diabetes incidence in Nigeria enhances the use of popular remedies that may interact with conventional therapies. The aqueous extracts of 27 popular Nigerian "antidiabetic" plants were tested for their effects on glutathione levels within HepG2 cells, P-glycoprotein (P-gp)-mediated Rh-123 efflux activity in Caco-2 vincristine-resistant cells, and modulation of glibenclamide transport in Caco-2 monolayers. The extract from significantly depleted intracellular glutathione at 100 µg/mL similarly to the reference buthionine sulphoximine (p < 0.05). Other 10 extracts raised glutathione levels. Eight extracts inhibiting P-gp efflux in a concentration-dependent manner (p < 0.01) were selected for further evaluation in a bi-directional transport model across Caco-2 monolayers: , and When interferences in paracellular transport were discarded, only 3 of them may be modulating the efflux ratio of glibenclamide (efflux ratio: 2.65 ± 0.13) in the same manner the reference drug verapamil (efflux ratio: 1.14 ± 0.25, p < 0.01) does: (efflux ratio: 1.70 ± 0.23, p < 0.01) (efflux ratio: 1.80 ± 0.25, p < 0.05), and (efflux ratio: 1.66 ± 0.10, p < 0.01). HPLC-UV analyses for P-gp inhibitors in these extracts revealed several phenolic compounds such as rutin, gallic acid, and ellagic acid reported to decrease P-gp expression and/or directly modify its function. In conclusion, some popular herbal medicines used by Nigerian diabetic patients are here shown to potentially affect glibenclamide absorption at concentrations that could be reached in the intestinal tract.
尼日利亚糖尿病发病率的上升促使人们更多地使用可能与传统疗法相互作用的常用药物。对27种常见的尼日利亚“抗糖尿病”植物的水提取物进行了测试，以研究它们对HepG2细胞内谷胱甘肽水平、Caco-2长春新碱耐药细胞中P-糖蛋白（P-gp）介导的Rh-123外排活性以及Caco-2单层细胞中格列本脲转运的影响。提取物在100μg/mL时能显著降低细胞内谷胱甘肽水平，与参考药物丁硫氨酸亚砜胺类似（p<0.05）。其他10种提取物能提高谷胱甘肽水平。选择8种以浓度依赖性方式抑制P-gp外排的提取物（p<0.01），在跨Caco-2单层细胞的双向转运模型中进行进一步评估： 、 和 。当排除细胞旁转运的干扰后，只有其中3种可能以与参考药物维拉帕米相同的方式调节格列本脲的外排率（外排率：2.65±0.13）（维拉帕米外排率：1.14±0.25，p<0.01）： （外排率：1.70±0.23，p<0.01）、 （外排率：1.80±0.25，p<0.05）和 （外排率：1.66±0.10，p<0.01）。对这些提取物中P-gp抑制剂的HPLC-UV分析显示，其中含有几种酚类化合物，如芦丁、没食子酸和鞣花酸，据报道这些化合物可降低P-gp表达和/或直接改变其功能。总之，尼日利亚糖尿病患者使用的一些常用草药在肠道中可能达到的浓度下，显示出可能影响格列本脲的吸收。
