**9. Future direction**

**8. Conclusion**

32 Biological Activities and Action Mechanisms of Licorice Ingredients

demonstrated increased survival rate.

Licorice has been used for pharmaceuticals, cosmetics, and food products as water‐soluble licorice extract that contains glycyrrhizin, the primary constituent having sweet‐taste and various biological activities. Recently, many studies have focused on the licorice ingredients except glycyrrhizin, about 300 phenolic compounds were found from licorice. We investigated licochalcone A extracted from *G. inflata* and glabridin from *G. glabra* in particular. The primary active ingredient isolated and extracted from *G. inflata* is licochalcone A, an oxygenated retrochalcone, which has been associated with various biological properties such as an antioxidant, antimicrobial, as well as anti‐inflammatory. As a result, licochalcone A showed several activities such as inhibitory effects of testosterone 5α‐reductase, lipase, and phospho‐ lipase A2, as well as androgen receptor antagonist, antimicrobial and SOD‐like activities, which relate to skin care, especially the suppression of acne formation and development. On the basis of this evidence, a trial of licochalcone A with acne patients was carried out and the efficacy was demonstrated clinically. The primary active ingredient of *G. glabra* is glabridin, a preny‐ lated isoflavonoid, which is one of the most studies licorice flavonoids, a comprehensive literature survey linked to its bioactivities. Glabridin has inhibitory effects on tyrosinase activity, a key enzyme in the production of melanins and melanization using cultured B16 melanoma cells. An open study of glabridin with melasma patients was conducted. The efficacy was evaluated by measuring skin lightness before and after therapy. Glabridin significantly improved after the therapy not only in melasma but also in lesions. The aerial parts of licorice have received scant interest. The few phytochemical investigations on the *G. glabra* leaves have shown the presence some flavonoids that are not in the roots. We found licorice leaf extract and its component, 6‐prenyl‐naringenin upregulated both SPTLC1 and SMPD1 mRNA expression related to ceramide synthesis as well as HMGCR mRNA expression related to the cholesterol synthesis. In addition, licorice leaf extract stimulated ceramide production in skin‐equivalent models and human skin and promoted HA synthesis by a mechanism that involves upregulation of HAS3 mRNA expression. These results suggested that the licorice leaf extract may be a useful ingredient for skin hydration and barrier repair. There are few reports on licorice extract and glycyrrhizin used in agriculture and fishery. We examined flavonoid‐rich water soluble licorice extract (WSLE) in agriculture and fishery uses. In agriculture, WSLE suppressed hyphal elongation of 12 kinds of plant pathogenic fungi and zoospore release from the conidia. In the pot test, WSLE suppressed the number of lesions in six kinds of plant diseases. As a result, we suggested WSLE has the control effects on some fungal diseases of vegetables such as cucumber, tomato, and sweet pepper. In fishery, WSLE and isoliquiritigenin inhibited the fish disease caused by bacteria, especially Gram‐positive bacteria. Effects of WSLE on nonspecific immune response of Japanese flounder were investi‐ gated. Oral administration of 5 or 50 mg/kgBW/day of WSLE for 2 weeks showed some significant enhance in humoral (hemolytic and lysozyme activities) and cellular (super oxide anion release and phagocytic activities) activities. After 10 days dietary treatment with WSLE, the fishes were challenged by intraperitoneal injection with *E. tarda*, WSLE‐treated fish

As for licorice resources, licorice plants are widely found growing wild in regions along the Silk Road. However, according to the recent overharvesting of wild licorice, its habitants are severely disturbed and many of them are degraded or undergoing desertification, especially in China. Therefore, licorice cultivation has been undertaken in China. However, in the present glycyrrhizin and flavonoid content of the cultivated licorice is lower than wild one. In the aim of securing a stable source of licorice, we have to study to obtain the cultivated licorice with same quality of wild licorice.

Over the past half‐century, we have been engaged in the development of licorice extracts and its components, and have been offering a number of useful and unique materials to our customers in medicinal, cosmetic, functionary food, and food industries. Elucidation of the constituents and biological activities of both underground and aerial parts in licorice plants have led to the development of many valuable licorice products for various industries. We are further expanding the potential of licorice.
