title: Effect of glycyrrhizic acid on rhein renal penetration: a microdialysis study in rats.
abstract: 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.
authors.affiliation: a College of Pharmaceutical Science, Zhejiang Chinese Medical University , Hangzhou , P.R. China and.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Wei
authors.affiliation: a College of Pharmaceutical Science, Zhejiang Chinese Medical University , Hangzhou , P.R. China and.
authors.forename: Jiani
authors.initials: J
authors.lastname: Guan
authors.affiliation: b National Clinical Research Base of Traditional Chinese Medicine, The First Affiliated Hospital, Zhejiang Chinese Medical University , Hangzhou , P.R. China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Ma
authors.affiliation: a College of Pharmaceutical Science, Zhejiang Chinese Medical University , Hangzhou , P.R. China and.
authors.forename: Yicong
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: a College of Pharmaceutical Science, Zhejiang Chinese Medical University , Hangzhou , P.R. China and.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ma
authors.affiliation: a College of Pharmaceutical Science, Zhejiang Chinese Medical University , Hangzhou , P.R. China and.
authors.forename: Fanzhu
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004357:Drug Synergism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000880:Anthraquinones; D019695:Glycyrrhizic Acid; C020491:rhein
keywords: Glycyrrhizic acid; in vivo microdialysis; renal penetration; rhein