Ju-Xiu He

Antispasmodic activity of licochalcone A, a species‐specific ingredient of Glycyrrhiza inflata roots

Licochalcone A, a species‐specific and characteristic retrochalcone ingredient of Glycyrrhiza inflata root, has been shown to possess multiple bioactive properties. However, its muscle relaxant activity has not been reported previously. Licochalcone A showed a concentration‐dependent relaxant effect on the contraction induced by carbachol (50% effective concentration (EC50) = 5.64 ± 1.61 μm). KCl (EC50 5.12 ± 1.68 μm), BaCl2 (EC50 1.97 ± 0.48 μm) and A23187 (EC50 2.63 ± 2.05 μm). Pretreatment with licochalcone A enhanced the relaxant effect of forskolin, an adenylyl cyclase activator, on the contraction in a similar manner to 3‐isobutyl‐1‐methylxanthine (IBMX), a phosphodiesterase (PDE) inhibitor. Furthermore, the IC50 (22.1 ± 10.9 μm) of licochalcone A against cAMP PDE was similar to that of IBMX (26.2 ± 7.4 μm). These results indicated that licochalcone A may have been responsible for the relaxant activity of G. inflata root and acted through the inhibition of cAMP PDE.

Influence of co-administered antibiotics on the pharmacokinetic fate in rats of paeoniflorin and its active metabolite paeonimetabolin-i from Shaoyao-Gancao-tang

The effects of orally co‐administered antibiotics on the pharmacokinetics of paeoniflorin (PF) and paeonimetabolin‐I (PM‐I), a bioactive metabolite derived from PF by intestinal bacteria, from the traditional Chinese formulation, Shaoyao‐Gancao‐tang (SGT), were investigated in rats to clarify the effect of administering SGT together with some synthetic drugs. Co‐administration of the antibiotics amoxicillin and metronidazole (AMPC‐MET) significantly increased the area under the plasma concentration versus time curve (AUC) of PF, whereas it markedly decreased that of PM‐I, to 2.6% of the normal AUC by administration of a single dose, and less than 1% by a 3‐day pretreatment. Similar effects were observed using the combination of ofloxacin with SGT. The PF‐metabolizing activity of intestinal bacteria was reduced to 16% and 33% of normal levels by treatment with AMPC‐MET and ofloxacin, respectively, which caused alterations of that degree in the extent of absorption of PF and PM‐I, but did not affect their rate of absorption or elimination. The present study suggests that it may not be appropriate to use SGT simultaneously with antibiotics such as AMPC‐MET or ofloxacin, and also reveals the important role of intestinal bacteria in the pharmacokinetics of the active components of this traditional Chinese formulation.

Bioavailability of glycyrrhizin from Shaoyao-Gancao-Tang in laxative-treated rats

Shaoyao‐Gancao‐Tang (SGT), a traditional Chinese formulation composed of Shaoyao (Paeoniae Radix) and Gancao (Glycyrrhizae Radix), is frequently used in conjunction with laxatives such as sodium picosulfate in colonoscopy to relieve abdominal pains. We have investigated the alterations of the bioavailability of glycyrrhizin when SGT was co‐administered with sodium picosulfate and we tried to identify a regimen that might minimize the alterations. Glycyrrhizin is one of the active glycosides in Gancao and SGT and is hydrolysed into the bioactive metabolite, 18β‐glycyrrhetic acid (GA) by intestinal bacteria following oral administration. We found that the maximum plasma concentration (Cmax) and the area under the mean concentration vs time curve from zero to 24 h (AUC0–24 h) of GA from a single dose of SGT administered 5 h after a single pretreatment with sodium picosulfate were significantly reduced to 15% and 20% of the control level in rats, respectively. These reductions were still significant four days after sodium picosulfate pretreatment, but were restored by repetitive administration of SGT following sodium picosulfate pretreatment. Similar reductions and recovery were observed for the glycyrrhizin‐metabolizing activity of intestinal bacteria in rat faeces. The results warrant clinical studies for co‐administration of laxatives such as sodium picosulfate and SGT.

Repetitive administration of Shaoyao-Gancao-tang to rats restores the bioavailability of glycyrrhizin reduced by antibiotic treatment.

Shaoyao‐Gancao‐tang (SGT), a traditional Chinese formulation, is often used together with antibiotics such as amoxicillin and metronidazole (AMPC‐MET) for the treatment of peptic ulcers in Japan. However, the bioavailability of glycyrrhizin (GL) in SGT is severely reduced by a single administration of AMPC‐MET, and the reducing effect continues for 12 days. GL is one of the major pharmacologically important glycosides in SGT and is transformed into the active metabolite 18β‐glycyrrhetic acid (GA) by intestinal bacteria in the gut, followed by absorption of the latter into the blood. In order to reduce the negative effect of AMPC‐MET on the bioavailability of GL, the optimum scheduling of the medications was examined. We found that the reduction in the plasma GA concentration and the GL‐metabolizing activity in faeces caused by a single dose of AMPC‐MET could be sharply attenuated by the repetitive administration of SGT for 4 days. The GA concentration and the GL‐metabolizing activity were strongly enhanced by further continuous administration of SGT. These findings suggest that repetitive administration of SGT starting 1 or 2 days after the administration of AMPC‐MET speeds the recovery of the bioavailability of GL in SGT. Similar strategies for administering medications may also be useful for combination therapy of antibiotics with other traditional Chinese formulations containing bioactive glycosides.

Da‐Chaihu‐Tang alters the pharmacokinetics of nifedipine in rats and a treatment regimen to avoid this

To investigate the influence of co‐administrated Da‐Chaihu‐Tang (DCT; a traditional Chinese formulation) on the pharmacokinetics of nifedipine, as well as the safe optimal dosing interval to avoid the adverse interactions.