Huang Bei-Bei, Li Guo-Feng, Ren Fei, Tang Zhong-Kun, Ma Hua-Fei, Sun Ya-Bin, Chen Li-Jing, Yang Ling
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Zhongguo Zhong Yao Za Zhi. 2008 Nov;33(21):2521-6.
To investigate the modulation of Glycyrrhiza inflata and Daphne genkwa on the permeability characteristics of rhodamine 123 (R123), one P-glycoprotein (P-gp) substrate, across the jejunum membranes. And then approach the possible permeability mechanism of the drugs after co-administration of G. inflata and D. genkwa in gastrointestinal tract.
The permeability of R123 or fluorescein sodium (CF) via Wistar rat jejunum membranes was evaluated by in vitro diffusion chamber system after oral administration of four different decoctions and 0.9% sodium chloride (20 mL x kg(-1)) for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry. The apparent permeability coefficient (P(app)) was calculated by the equation P(app) = dQ/d(t) x (1/A x C0), where P(app) was expressed in cm/s, dQ/dT was the slope of the linear portion of the permeation curves, A was the diffusion area, and C0 was the initial concentration of rebamipide in the donor side, and then compare their differences were compared with control group.
After oral administration of G. inflata decoction, D. genkwa decoction and decoction of the combination of the previous decoctions, the absorptive directed transport of R123 was significantly increased (P < 0.05, compared with control group). On the other hand, D. genkwa could also decrease the permeability of secretory directed transport (P(app) = 2.98 +/- 0.59), while no action of G. inflata was found on the secretory transport of R123 ( P(app) = 5.24 +/- 3.98) across the jejunum tissues, while P(app) of control group was 4.38 +/- 1.18. Meanwhile, G. inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group.
G. inflata may slightly inhibit P-glycoprotein function in the intestinal membrane, while D. genkwa may be a relatively strong inhibitor of P-gp. For another, some compositions in D. genkwa inhibit P-gp function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-gp was enhanced by combination of G. inflata and D. genkwa, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of G. inflata and D. genkwa.
研究胀果甘草和芫花对P-糖蛋白（P-gp）底物罗丹明123（R123）跨空肠黏膜通透性特征的影响。进而探讨胀果甘草与芫花合用时药物在胃肠道可能的通透机制。
通过体外扩散池系统，在给予4种不同水煎剂及0.9%氯化钠（20 mL·kg⁻¹）灌胃1周后，评估Wistar大鼠空肠黏膜对R123或荧光素钠（CF）的通透性。采用荧光分光光度法测定R123或CF的浓度。表观渗透系数（P(app)）由公式P(app)=dQ/d(t)×(1/A×C0)计算得出，其中P(app)以cm/s表示，dQ/dT为渗透曲线线性部分的斜率，A为扩散面积，C0为供体侧瑞巴派特的初始浓度，然后将其与对照组进行差异比较。
灌胃胀果甘草水煎剂、芫花水煎剂及二者合用水煎剂后，R123的吸收性定向转运显著增加（与对照组相比，P<0.05）。另一方面，芫花也可降低分泌性定向转运的通透性（P(app)=2.98±0.59），而胀果甘草对R123跨空肠组织的分泌性转运无作用（P(app)=5.24±3.98），对照组的P(app)为4.38±1.18。同时，胀果甘草对CF跨空肠组织的转运无影响，而其他三组与对照组相比可降低CF的通透性。
胀果甘草可能对肠黏膜中的P-糖蛋白功能有轻微抑制作用，而芫花可能是一种较强的P-gp抑制剂。另外，芫花中的某些成分抑制P-gp功能，另一些成分则增强肠黏膜细胞间紧密连接以降低CF的通透性。基于结果，胀果甘草与芫花合用时对P-gp的抑制作用增强，这可能是二者合用时产生毒性的机制之一。
