[Effect of Glycyrrhiza inflata and Daphne genkwa on permeabilities of rhodamine 123, a P-glycoprotein substrate across rat jejunum membranes in vitro].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Huang
Bei-Bei
BB
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Li
Guo-Feng
GF
Ren
Fei
F
Tang
Zhong-Kun
ZK
Ma
Hua-Fei
HF
Sun
Ya-Bin
YB
Chen
Li-Jing
LJ
Yang
Ling
L
D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D032364:Daphne / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000493:pharmacokinetics*
D004365:Drugs, Chinese Herbal; D020112:Rhodamine 123