Pharmacokinetic incompatibility of the Huanglian-Gancao herb pair

Abstract

Background: Pharmacokinetic interaction is one of the most important indices for the evaluation of the compatibility of herbal medicines. Both Gancao (Glycyrrhizae Radix et Rhizoma) and Huanglian (Coptidis Rhizoma) are commonly used traditional Chinese medicines (TCMs). In this study, the influence of Gancao on the pharmacokinetics of Huanglian was systematically studied by using berberine as a pharmacokinetic marker. Methods: Extracts of the herbal pieces of Huanglian and the herb pair (Huanglian plus Gancao) were prepared with boiling water. The concentration of berberine in the samples was analyzed using liquid chromatography-mass spectrometry. The total amounts of berberine in all extract samples were compared. Comparative pharmacokinetic studies of Huanglian and the herb pair were conducted in ICR mice. In vitro berberine absorption and efflux were studied using mice gut sacs. The equilibrium solubility of berberine in the extracts was determined. The in vitro dissolution of berberine was comparatively studied using a rotating basket method. Results: Gancao significantly reduced berberine exposure in the portal circulation (425.8 ng•h/mL vs. 270.4 ng•h/mL) and the liver (29,500.8 ng•h/mL vs. 15,422.4 ng•h/mL) of the mice. In addition, Gancao decreased the peak concentration (C max) of berberine in the portal circulation (104.3 ng•h/mL vs. 76.5 ng•h/mL) and liver (4926.1 ng•h/mL vs. 2642.8 ng•h/mL) of mice. Significant influences of Gancao on the amount of berberine extracted (32% reduction), the solubility of berberine (34.7% compared with the control group), and dissolution (88.7% vs. 66.1% at 15 min in acid buffer and 68% vs. 51.8% at 15 min in phosphate buffer) were also revealed. Comparative pharmacokinetic studies in ICR mice indicated that the formation of sediment was unfavorable in terms of berberine absorption (345.3 ng•h/mL vs. 119.8 ng•h/mL). Conclusions: Gancao was able to reduce intestinal absorption and in vivo exposure of berberine in Huanglian via the formation of sediment, which caused reductions in the extracted amount, solubility, and dissolution of berberine.

Pharmacokinetic study on the effect of ligustrazine–tangeretin co‐administration on the pharmacokinetics of ligustrazine and its potential mechanism in rats

“…Zhang et al employed berberine as the pharmacokinetic marker to investigate the potential interaction between Gancao and Huanglian. It was found that the intestinal absorption and exposure of Huanglian were suppressed by Gancao caused by the formation of sediment, which reduced the solubility and extracted amount of berberine 28 . The co‐consumption of Gancao with glycyrrhetinic acid induced the sodium‐water retention side effects, while the combination of Kushen with Gancao could slow down the absorption and enhance the metabolism of glycyrrhetinic acid 29 …”

Pharmacokinetics and Pharmacodynamics of Huanglian-Houpo Decoction Based on Berberine Hydrochloride and Magnolol Against H1N1 Influenza Virus

“…The results revealed that due to the different intestinal absorption, the bioavailability of CRE and CR-GRE is much lower than that of pure berberine [ 27 ]. Zhang et al’s research indicated that Gancao was able to reduce the intestinal absorption of berberine in Huanglian through reductions in the extracted amount, solubility and release from the herb extract [ 28 ]. Modern natural medicine research shows that the main ingredients in Huanglian-Houpu decoction are berberine and magnolol.…”

Several major herb pairs containing Coptidis rhizoma: a review of key traditional uses, constituents and compatibility effects

“…When CR and GRR are combined, the glycyrrhizin reacts to form berberine glycyrrhizate salt, which will make the bitter taste of berberine disappear and play a role in correcting the taste. The precipitation slowly decomposes in the body and exerts its effects, which plays a role in moderating and prolonging the efficacy of herbs ( Zhang et al, 2020 ). On the one hand, when comparing the retention times of chemical components in the chromatograms of single herbs and herb pairs through qualitative analysis, the results indicated that the changes in chemical constituents in the compound were not simply additive.…”