Pharmaceutical Evaluation of Glycyrrhiza uralensis Roots Cultivated in Eastern Nei-Meng-Gu of China

Abstract

Recent environmentally irresponsible over-collection of wild Glycyrrhiza plants, which produce a well-known medicinal licorice (Glycyrrhizae Radix, , Gancao in Chinese and Kanzo in Japanese), is one of the factors inducing desertification. It is reported that the World Health Organization (WHO) plans to introduce Good Field Collection Practice (GFCP) to conserve the natural environment. In 2000, the Chinese government imposed restrictions on the collection of wild Glycyrrhiza plants. Gancao is most frequently used in a famous traditional Chinese medical formulary Shan-HanLun ( ) 2) and has been used for allergic-inflammatory, gastrointestinal and liver disorders in both traditional Chinese and modern medicine. 3,4) With the increasing demand for Gancao and the decline of wild Glycyrrhiza resources, cultivated Glycyrrhiza roots have attracted attention as an additional source of Gancao. This growing interest in a new cultivated source requires a clarification of the equivalency between the cultivated Glycyrrhiza roots and concurrent Gancao. We previously reported on glycyrrhizin (GL)-content in G. uralensis roots cultivated in the eastern Nei-Meng-Gu ( ) of China, which is the habitat of G. uralensis and the major source of Dongbei-Gancao ( , Tohoku-Kanzo in Japanese).5) It was the first report that the GL-content of 4-year-old G. uralensis adventitious roots 6) exceeds the Japanese Pharmacopoeia XIV (JP XIV) standard (2.5% or more). Our cultivation study has been continued and we have obtained higher GL-content and yield of roots as well as adequate ingredients-composition similar to concurrent medicinal Gancao prepared from wild G. uralensis roots.In the present study, we describe the pharmaceutical properties of the cultivated G. uralensis roots. The overall gross similarities in chemical ingredients between the cultivated roots and Dongbei-, Xibei-( , Seihoku-Kanzo in Japanese), Xinjiang-Gancao ( , Shinkyo-Kanzo in Japanese) and wild G. uralensis roots were examined by comparing the HPLC fingerprints (chromatograms) including the GL peak. The analysis of HPLC fingerprints was further examined quantitatively by hierarchical cluster analysis (HCA) and principal component analysis (PCA). In addition to the chemical study, pharmacological and pharmacokinetical studies play an important role to assure safety and effective clinical use of a new medicinal candidate. The pharmacological properties were examined using IgE-mediated triphasic skin reaction in mice.7) The plasma concentration-time profile of glycyrrhetic acid (GA), an antiallergic 8) metabolite biotransformed from GL by intestinal bacteria, was also examined. MATERIALS AND METHODSCultivated G. uralensis Roots and Comparative Samples As shown in Fig. 1, 4-and 5-year-old roots cultivated in the same field in eastern Nei-Meng-Gu as in the previous report 5) were used. The botanical origin of the cultivated plant was identified previously 5) to be G. uralensis by referring to the morphological characteristics of flowers and fruits described.9) The same Dongb...

Economic importance of licorice

“…The recent over-utilization of wild Glycyrrhiza plants has resulted in a reduction in the natural reserves and desertification of the habitats of these plants, especially in China. Thus, in 2000, the Chinese government enforced restrictions on the collection of wild licorice, leading to a shortage of licorice in the market (Yamamoto et al 2005). Glycyrrhiza cultivation has been undertaken to compensate for the reduction in the natural reserves of Glycyrrhiza plants; however, the glycyrrhizin content of the licorice obtained from these plants is often low.…”

“…Glycyrrhiza cultivation has been undertaken to compensate for the reduction in the natural reserves of Glycyrrhiza plants; however, the glycyrrhizin content of the licorice obtained from these plants is often low. Recently, researchers were successful in producing 4-year-old adventitious roots with glycyrrhizin levels that conformed to the Japanese Pharmacopeia standard (not less than 2.5%) (Yamamoto et al 2003, Yamamoto andTani 2005); moreover, licorice obtained from cultivated plants was also imported from Australia as described above (Table 1). Further studies are required to devise a method for increasing the glycyrrhizin content in the roots of cultivated Glycyrrhiza plants and to obtain a Glycyrrhiza strain that produces high amounts of glycyrrhizin (Yamamoto and Tani 2005).…”

“…Recently, researchers were successful in producing 4-year-old adventitious roots with glycyrrhizin levels that conformed to the Japanese Pharmacopeia standard (not less than 2.5%) (Yamamoto et al 2003, Yamamoto andTani 2005); moreover, licorice obtained from cultivated plants was also imported from Australia as described above (Table 1). Further studies are required to devise a method for increasing the glycyrrhizin content in the roots of cultivated Glycyrrhiza plants and to obtain a Glycyrrhiza strain that produces high amounts of glycyrrhizin (Yamamoto and Tani 2005). The cDNA sequences of the enzymes involved in glycyrrhizin biosynthesis have been reported; therefore, the possibility of using metabolic engineering to generate glycyrrhizin-producing plants or microorganisms seems promising and should be considered in future studies (Hayashi et al 2001, Seki et al 2008.…”

Isolation, cloning and bioinformatics analysis of β-amyrin 11-oxidase coding sequence from licorice

“…β-amyrin oxidation in C-11 and C-30 positions produced glycyrrhizin, which this oxidation is blocked in cell culture and instead β-amyrin is oxidized in C-22 and C-24 positions and converted to soyasapogenol B. On the other hand, the glycyrrhizin processing is related to the collection of perennial roots from the ground, and in some parts of world, non-harvesting rules have been applied due to indiscriminate harvesting of roots (Yamamoto and Tani, 2005). Therefore, it can be suggested that this gene plays a key role in engineering the competitive pathway of production of glycyrrhizin and soyasaponin and converts intermediate compound of β-amyrin to glycyrrhizin.…”

Comparative Analysis of Ten Strains of Glycyrrhiza uralensis Cultivated in Japan

“…Thus cultivation of G. uralensis was undertaken to substitute for the wild resources. [4][5][6][7] Extensive chemical studies revealed that the roots and stolons of Glycyrrhiza plants contain not only glycyrrhizin but also many flavonoids, 3,8) including species-specific flavonoids, 9,10) such as glycycoumarin in G. uralensis. In addition, chemical variations in leaves of Glycyrrhiza plants were reported, 11,12) and these variations are useful in identifying the species and strains of Glycyrrhiza plants.…”