**5. Future direction**

We sometimes experience that purification of active ingredients leads to significant loss of the biological activity. Furthermore, the amount of ingredients is different from one batch to another depending on where they are harvested. Therefore, it is essential to reconstruct the best sets of active ingredients for the standardization of the contents. First step to accomplish this is to investigate the relationship between the biological activity of structurally related com‐ pounds and chemical descriptors, using quantitative structure‐activity relationship (QSAR) analysis. Once the best 3D structure is predicted, such compounds should be quickly synthe‐ sized to confirm its biological activity. This process is repeated until the satisfactory results are obtained. The next step is to determine the best combination of ingredients (**Figure 3**).

The relative potency of ingredients may depend on the type of target cells. For example, licorice flavonoids showed potent anti‐HSV activity, while they were inactive against HIV infection [29]. During isolation of active ingredients, some aggregations between ingredients may happen [30]. Accumulation and analysis of such data are crucial to manufacture the best Kampo medicine.

Using QASR analysis, we recently found that anti‐HSV activity of 19 flavonoids including 10 licorice flavonoids correlated well with six chemical descriptors that represent polarizability

**Figure 3.** Chart flow to select the best combination of licorice ingredients. Each symbol is any compound. The same shapes indicated the compounds with similar structure.

(MATS5p, GATS5p), ionization potential (GATS5i), number of ring systems (NRS), atomic number (J\_Dz(Z)) and mass (J\_Dz(m) (p < 0.0001). This result suggests that the physico‐ chemical properties, rather than the category of compound, are important factors in deter‐ mining the anti‐HSV activity [29]. The possibility that their target site may be common is under investigation.

It is expected that in the future, alternative therapy with Kampo medicines will be versioned up, in synchronization with the improvement in the personalized medicine based on the gene information.
