Tadato Tani

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.

Preventive effects of a traditional Chinese formulation, Chaihu-jia-Longgu-Muli-tang, on intimal thickening of carotid artery injured by balloon endothelial denudation in rats.

We report here that the traditional Chinese formulation, Chaihu‐jia‐Longgu‐Muli‐tang (CLM), significantly inhibited the increase in intimal thickening in rat carotid artery injured by balloon endothelial denudation, which mimics many aspects of restenosis after percutaneous coronary intervention (PCI) in humans. CLM, Saiko‐ka‐Ryukotsu‐Borei‐to in Japanese, is commonly prescribed for symptoms accompanying hypertension and atherosclerosis in Japanese kampo medical care. CLM administered orally 1 week before and 1, 4 and 8 weeks after balloon injury inhibited the increase in intimal area, intimal/medial ratio and stenosis ratio. To our knowledge, this is the first report demonstrating inhibitory effects of a traditional Chinese formulation on intimal thickening of carotid artery after balloon injury. It is worth noting that CLM maintained its inhibitory effect up to 8 weeks after balloon injury. The reduction in intimal thickening by CLM could have resulted from inhibition of intimal smooth muscle cell proliferation, which was assessed by immuno‐histochemical analysis using monoclonal antibody against proliferating cell nuclear antigen. Therefore, CLM may be a favourable candidate for prevention of restenosis after PCI. Moreover CLM may have a therapeutic value in the prevention of atherosclerosis, because restenosis after PCI is considered to be an accelerated atherosclerosis.

Pharmaceutical evaluation of liquorice before and after roasting in mice

Liquorice has been used for allergic‐inflammatory and liver disorders in both traditional Chinese and modern medicine. In traditional Chinese formulations, it is mainly roasted liquorice that has been used rather than un‐roasted liquorice. We have compared the pharmaceutical characteristics of liquorice before and after roasting to clarify the pharmaceutical significance of the roasting. Although roasted liquorice contained less glycyrrhizin (an anti‐allergic component) than un‐roasted liquorice, the inhibitory potency of roasted liquorice extract (200 mg kg−1) on immunoglobulin E (IgE)‐mediated triphasic ear swelling in mice was much greater compared with un‐roasted liquorice. To search for additional active ingredients, roasted liquorice extract was subjected to gel‐chromatography to give an anti‐allergic fraction (Fa) of molecular weight ranging from 15000 to 200000 or more, in which glycyrrhizin was not detected. By testing the activity of the various fractions, it was proved that the anti‐allergic effect of roasted liquorice was due to glycyrrhizin, its metabolite glycyrrhetic acid, and the Fa fraction. The inhibitory potency of the Fa fraction (15 and 75 mg kg−1) prepared from roasted liquorice was stronger than that prepared from un‐roasted liquorice. Therefore, a pharmaceutical implication of roasting the liquorice seems to be associated with an increase in the anti‐allergic property of the Fa fraction. It is notable that oral administration of the high molecular mass fraction (Fa) significantly inhibited IgE‐mediated ear swelling six days after challenge at doses as low as 3, 15 or 75 mg kg−1.

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.

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.