1. Rhein (RH), a primary active component isolated from rhubarb, is effective in protecting against the progression of diabetic nephropathy (DN) progression. Glycyrrhizic acid (GA), an active constituent of liquorice, is also considered to be a protective agent against DN. Here, we evaluated the effect of GA on the renal penetration of RH in rats. 2. Plasma and renal pharmacokinetics were profiled to estimate kidney penetration. After rats were anesthetized, the carotid artery was used for blood collection and a microdialysis probe was inserted into the kidney cortex to collect dialysate samples. 3. When co-administered with GA, the Vss and CL values of RH in plasma increased by 25% and 34%, respectively. The Cmax in kidney dialysates significantly increased 1.3-fold (p<0.05). There was no change in AUC0-∞ in kidney dialysates, but a significant decrease (2×fold) in the plasma was observed. The AUC0-∞kidney/AUC0-∞plasma ratio of RH, representing kidney penetration, increased by 1.4-fold in the group pre-treated with GA compared to the RH alone group. 4. These results demonstrate that GA increases the renal penetration of RH efficiently and may exert a synergistic effect, although the molecular mechanism of interaction requires further investigation.
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