**Herbal Drugs in Traditional Japanese Medicine**

## Tsutomu Hatano

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/53126

## **1. Introduction**

Medicinal herbs are used in the context of ethnic traditions in various regions of the world. Although modern medicine, based on Western medicine, is practiced in developed coun‐ tries, traditional medicine is also an important part of treatment in Asian countries.

Traditional Chinese medicine (TCM) influences traditional medicine in Asian countries as a function of the cultural and historical relationships between each country and China. That is, traditional medicine has developed in each country under the influence of TCM in the context of its own cultural background.

This chapter examines traditional Japanese medicine (TJM), an alternative form of medicine used in Japan. Although acupuncture, moxibustion, and several related medical practices al‐ so play important roles in TJM, herbal medicine, as the most characteristic treatment within TJM, is the focus of this chapter.

## **2. Relationship between TJM and TCM**

Western medicine often regards patients as sets of individual organs, and illnesses are often at‐ tributed to pathogens or morbid organs that should be removed. However, Asian traditional medicine, including TJM and TCM, understand patients from a holistic perspective that em‐ phasizes the importance of balancing and harmonizing the entire patient, including her or his mind and body. Asian forms of medicine explain changes in symptoms in terms of causes, and treatments are prescribed based on a view of diseases as dynamic processes [1,2].

Basic medical concepts are common to both TJM and TCM, and practitioners of these disci‐ plines arrive at diagnoses via four basic approaches.

© 2012 Hatano; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**1.** Visual examination: Observation of the status of the face, tongue, skin, and behavior of the patient.

Historical books, such as Koji-ki (Records of Ancient Matters) (712), include descriptions of the use of reed mace (*Typha* spp., Fig. 2) for injury. Koji-ki records historical matters or folk‐

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Cultural exchanges, including those involving envoys to the Tang Dynasty (7th–9th centu‐ ries), and trade with China brought various crude drugs to Japan. Some of these drugs are the "Shosoin drugs" of today.TJM was practiced by Buddhism priests during those eras.

**Figure 1.** Examples of plants used as Japanese folk medicines. (a) *Geranium thunbergii* Sieb. et Zucc. (family Gerania‐

Chinese medicine changed based on historical changes in the dynasties, and the Chinese medicine of each era, until the present one, has influenced Japanese medicine. Chinese med‐ icine was introduced during the Yuan dynasty in Japan and was practiced by Sanki Tashiro (1465–1537) and his successors, including Dosan Manase (1507–1594), who developed the medicines. They were known as the Gosei-ho-ha (the Latter-day Medicine School). The med‐ icine taught by this school was based on two principles [Yin (active/positive) and Yang (in‐ active/negative)] combined with five elements (wood, fire, earth, metal, and water). The pharmacological characteristics of the herbal/crude drugs were separated into five tastes (pungent, sweet, sour, bitter, and salty) based on the five-element theory. Other characteris‐ tics, such as emotions, which may affect illnesses, are also attributed to the five elements

A trend toward a return to the fundamentalism of Confucianism appeared in China during the Ming Dynasty (14th–17th centuries), and an analogous fundamentalism was also seen in Chinese medicine. Some leaders in this field advocated reliance on the ideas or spiritual con‐ tent related to medicine in the Shokan-zatsubyo-ron (*Shang-Han-Za-Bing-Lun* in Chinese, "Treatise on Cold Damage Disorders and Accompanied Various Diseases") edited by

ceae), and (b) *Mallotus japonicas* Muell.-Arg. (family Euphorbiaceae)

Zhong-Jing Zhang during the Han Dynasty (BC200–AD200).

(Table 1) [2, 3].

lores of the prehistoric ages in Japan.


However, differences between TCM and TJM exist with regard to how each makes diagno‐ ses and prescribes treatment.

Diagnosis in the TCM treatment involves the following steps:


In contrast, TJM diagnoses, particularly those based on the Koho school, involve selecting an appropriate prescription; each prescription corresponds to specific symptoms associated with the constituents of herbal drugs. The most characteristic feature of TJM is that diagno‐ sis is directly linked to selection of a prescription. The differences between TJM and TCM became especially pronounced during the Edo era in the 17th–19th centuries. Indeed, impor‐ tant diagnostic concepts often have different meanings in TJM and TCM. Thus, different uses of the concepts result in confusion, even among apprentices in TJM.

## **3. Short history of TJM**

Drug use has long been part of the ethnic traditions in Japan, and various folk medicines have been applied in these contexts. The Geranium herb (over-ground part of *Geranium thunbergii* Sieb. et Zucc.), which is used as an anti-diarrheic, and Mallotus bark (bark of *Mal‐ lotus japonicus* Muell.-Arg.), which is used for stomach disorders, are examples of herbal drugs introduced into the Japanese Pharmacopeia (Fig. 1). The leaf of *Quercus stenophylla* (Urajiro-gashi in Japanese) is used for urinary tract calculi.

Historical books, such as Koji-ki (Records of Ancient Matters) (712), include descriptions of the use of reed mace (*Typha* spp., Fig. 2) for injury. Koji-ki records historical matters or folk‐ lores of the prehistoric ages in Japan.

**1.** Visual examination: Observation of the status of the face, tongue, skin, and behavior of

**2.** Auditory examination: Auscultation of the patient speaking, sighing and wheezing and

**4.** Tactile examination: Evaluation of the pulse and determination of abdominal status.

However, differences between TCM and TJM exist with regard to how each makes diagno‐

**1.** Gathering data about symptoms to determine a diagnosis. Ba-bang-bian-zheng (in Chi‐ nese, assignment of body conditions to one of the eight principal states) is an important step in the diagnostic process of TCM and is based on discriminating between members of pairs: ying (negativity/hypo-functioning) and yang (positivity/hyper-functioning), xu (deficiency) and shi (excessiveness), han (cold/chills) and re (heat/fever), and biao (exte‐

**2.** Identifying the cause of the illness based on the theory underpinning TCM, including

**3.** Determining the appropriate prescription based on the theory underpinning TCM. Ac‐ cording to TCM, herbal prescriptions are based on imbalances in the viscera and bow‐

In contrast, TJM diagnoses, particularly those based on the Koho school, involve selecting an appropriate prescription; each prescription corresponds to specific symptoms associated with the constituents of herbal drugs. The most characteristic feature of TJM is that diagno‐ sis is directly linked to selection of a prescription. The differences between TJM and TCM became especially pronounced during the Edo era in the 17th–19th centuries. Indeed, impor‐ tant diagnostic concepts often have different meanings in TJM and TCM. Thus, different

Drug use has long been part of the ethnic traditions in Japan, and various folk medicines have been applied in these contexts. The Geranium herb (over-ground part of *Geranium thunbergii* Sieb. et Zucc.), which is used as an anti-diarrheic, and Mallotus bark (bark of *Mal‐ lotus japonicus* Muell.-Arg.), which is used for stomach disorders, are examples of herbal drugs introduced into the Japanese Pharmacopeia (Fig. 1). The leaf of *Quercus stenophylla*

uses of the concepts result in confusion, even among apprentices in TJM.

(Urajiro-gashi in Japanese) is used for urinary tract calculi.

**3.** Interview: Questions posed to the patient about the history of the illness.

Diagnosis in the TCM treatment involves the following steps:

the patient.

50 Alternative Medicine

ses and prescribes treatment.

rior) and li (interior).

**3. Short history of TJM**

els.

the five-element theory described later.

examination of the patient's olfaction.

Cultural exchanges, including those involving envoys to the Tang Dynasty (7th–9th centu‐ ries), and trade with China brought various crude drugs to Japan. Some of these drugs are the "Shosoin drugs" of today.TJM was practiced by Buddhism priests during those eras.

**Figure 1.** Examples of plants used as Japanese folk medicines. (a) *Geranium thunbergii* Sieb. et Zucc. (family Gerania‐ ceae), and (b) *Mallotus japonicas* Muell.-Arg. (family Euphorbiaceae)

Chinese medicine changed based on historical changes in the dynasties, and the Chinese medicine of each era, until the present one, has influenced Japanese medicine. Chinese med‐ icine was introduced during the Yuan dynasty in Japan and was practiced by Sanki Tashiro (1465–1537) and his successors, including Dosan Manase (1507–1594), who developed the medicines. They were known as the Gosei-ho-ha (the Latter-day Medicine School). The med‐ icine taught by this school was based on two principles [Yin (active/positive) and Yang (in‐ active/negative)] combined with five elements (wood, fire, earth, metal, and water). The pharmacological characteristics of the herbal/crude drugs were separated into five tastes (pungent, sweet, sour, bitter, and salty) based on the five-element theory. Other characteris‐ tics, such as emotions, which may affect illnesses, are also attributed to the five elements (Table 1) [2, 3].

A trend toward a return to the fundamentalism of Confucianism appeared in China during the Ming Dynasty (14th–17th centuries), and an analogous fundamentalism was also seen in Chinese medicine. Some leaders in this field advocated reliance on the ideas or spiritual con‐ tent related to medicine in the Shokan-zatsubyo-ron (*Shang-Han-Za-Bing-Lun* in Chinese, "Treatise on Cold Damage Disorders and Accompanied Various Diseases") edited by Zhong-Jing Zhang during the Han Dynasty (BC200–AD200).

However, Yoshimasu's most important contribution concerned the use of herbal prescrip‐ tions. During the Edo era, Honzo-komoku (*Ban-Cao-Gang-Mu* in Chinese, "Compendium of Materia Medica") (1590, Ming Dynasty), written by Shi-Zhen Li (1518–1593), was the most authoritative book in Asia, including Japan, to describe the efficacy of herbal drugs. Howev‐ er, Yoshimasu decided to revise sections on the effects of herbal drugs as he thought that the descriptions in the book were useless in terms of practical clinical applications. Yoshimasu thought that the descriptions were written under the influence of delusions/superstitions

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53

Thus, he first addressed cases in which major prescriptions are used for Shokan-zatsubyoron. Shokan-zatsubyo-ron is composed of two parts, which were identified separately. Sho‐ kan-ron (*Shang-Han-Lun* in Chinese, "Treatise of Cold Damage Disorders"), which addresses acute feverish diseases and Kinki-yoryaku (*Jin-Gui-Yao-Lue* in Chinese, "Essential Prescrip‐

He also added discussion based on his clinical experience concerning the uses of each pre‐ scription. These were gathered in Ruiju-ho ("a classified collection of prescriptions"). In Sho‐ kan-zatsubyo-ron, the author indicated the uses of each prescription during the course of an illness. However, the author did not explain the reasons for using each prescription, but in‐ stead stated that the physician should "just use it in exemplar cases." In this way, Todo Yoshimasu clarified the actions of the prescriptions by analyzing the kind of case in which it

Yoshimasu then began to collect the herbal drugs to be used in prescriptions. He gathered descriptions of the prescriptions containing each herbal drug from Shokan-zatsubyo-ron and discussed the effects of each herbal drug based on commonalities in the properties of prescriptions containing the drug. In other words, common symptoms referenced in the de‐ scriptions of the prescriptions were regarded as related to the herbal drug that was common to the prescriptions. He learned about the efficacy of each of the herbal drugs from Shokanzatsubyo-ron by comparing it with his clinical experience. Such knowledge was collected in

For example, the action of the herbal drug licorice is discussed as follows: Although licorice (root with stolon of *Glycyrrhiza uralensis* Fisch. or *G. glabra* L.) is included in many prescrip‐ tions, prescriptions containing a particularly large quantity of licorice are shakuyaku-kanzoto ("peony and licorice combination"), kanzo-kankyo-to ("licorice and ginger combination"), kanzo-shashin-to ("pinellia and licorice combination"), and kan-baku-taiso-to ("licorice and jujube combination"). Based on the cases described in the literature that involved use of these prescriptions and on comparisons with his own clinical experience, he concluded that

He next listed the effects of each prescription based on the actions of the constituent crude drugs he had examined. These findings are summarized in the book Ho-kyoku ("The Ulti‐

For example, the keishi-to ("cinnamon combination") prescription, which is composed of cinnamon (bark of *Cinnamomum cassia* Blume), peony (root of *Paeonia lactiflora* Pall.), licorice,

tions as A Treasure Box"), which addresses sub-acute and chronic diseases.

based on ethnic religion.

should be used.

Yaku-cho ("Properties of Herbal Drugs").

mate Properties of the Prescriptions").

licorice suppressed various otherwise imminent symptoms.

**Figure 2.** *Typha latifolia* L. (Typhaceae)


**Table 1.** Five-element theory based on traditional Chinese medicine (TCM) and Gosei-ho-ha medicine in traditional Japanese medicine (TJM)

These ideas affected the leading physicians in Japan, who stressed that medicine in Japan should be based on Shokan-zatsubyo-ron, which was established in the Han Dynasty. Gon‐ zan Goto (1659–1733) was such a physician, and he insisted on considering diseases to be based on ki (*qi* in Chinese) stagnation. Goto mentored many younger physicians, who were known as Koho-ha (fundamentalists). Toyo Yamawaki, one such physician, guided dissec‐ tions and prepared a book entitled Zo-shi ("Records of Human Organs"), in which he clari‐ fied the differences between the actual structure of the human body and the structure depicted by TCM. Followers of this school insisted on practical evidence or actual results from medical trials. Todo Yoshimasu established a new approach to medicine based on this foundation.

#### **4. Yoshimasu's TJM**

Todo Yoshimasu established a new approach to medicine based on the notions described above. He was regarded as a highly skilled physician and contributed to new develop‐ ments in the area of medical diagnosis. He stressed the importance of the abdomen, in addition to that of the radial artery pulse, in diagnosis. He actually simplified the causes of various diseases based on his unique "one-poison theory" and thereby eliminated con‐ ceptual confusion [1, 3-5].

However, Yoshimasu's most important contribution concerned the use of herbal prescrip‐ tions. During the Edo era, Honzo-komoku (*Ban-Cao-Gang-Mu* in Chinese, "Compendium of Materia Medica") (1590, Ming Dynasty), written by Shi-Zhen Li (1518–1593), was the most authoritative book in Asia, including Japan, to describe the efficacy of herbal drugs. Howev‐ er, Yoshimasu decided to revise sections on the effects of herbal drugs as he thought that the descriptions in the book were useless in terms of practical clinical applications. Yoshimasu thought that the descriptions were written under the influence of delusions/superstitions based on ethnic religion.

Thus, he first addressed cases in which major prescriptions are used for Shokan-zatsubyoron. Shokan-zatsubyo-ron is composed of two parts, which were identified separately. Sho‐ kan-ron (*Shang-Han-Lun* in Chinese, "Treatise of Cold Damage Disorders"), which addresses acute feverish diseases and Kinki-yoryaku (*Jin-Gui-Yao-Lue* in Chinese, "Essential Prescrip‐ tions as A Treasure Box"), which addresses sub-acute and chronic diseases.

**Figure 2.** *Typha latifolia* L. (Typhaceae)

52 Alternative Medicine

Japanese medicine (TJM)

foundation.

**4. Yoshimasu's TJM**

ceptual confusion [1, 3-5].

**Element** *Mu (Wood) Huo (Fire) Tu (Earth) Jin (Metal) Shui (Water)*

Bowel Gallbladder Small intestine Stomach Large intestine Urinary bladder

**Table 1.** Five-element theory based on traditional Chinese medicine (TCM) and Gosei-ho-ha medicine in traditional

These ideas affected the leading physicians in Japan, who stressed that medicine in Japan should be based on Shokan-zatsubyo-ron, which was established in the Han Dynasty. Gon‐ zan Goto (1659–1733) was such a physician, and he insisted on considering diseases to be based on ki (*qi* in Chinese) stagnation. Goto mentored many younger physicians, who were known as Koho-ha (fundamentalists). Toyo Yamawaki, one such physician, guided dissec‐ tions and prepared a book entitled Zo-shi ("Records of Human Organs"), in which he clari‐ fied the differences between the actual structure of the human body and the structure depicted by TCM. Followers of this school insisted on practical evidence or actual results from medical trials. Todo Yoshimasu established a new approach to medicine based on this

Todo Yoshimasu established a new approach to medicine based on the notions described above. He was regarded as a highly skilled physician and contributed to new develop‐ ments in the area of medical diagnosis. He stressed the importance of the abdomen, in addition to that of the radial artery pulse, in diagnosis. He actually simplified the causes of various diseases based on his unique "one-poison theory" and thereby eliminated con‐

Viscera Heart Liver Spleen Lung Kidney

Taste Sour Bitter Sweet Pungent Salty Emotion Joy Anger Anxiety Sorrow Fear

He also added discussion based on his clinical experience concerning the uses of each pre‐ scription. These were gathered in Ruiju-ho ("a classified collection of prescriptions"). In Sho‐ kan-zatsubyo-ron, the author indicated the uses of each prescription during the course of an illness. However, the author did not explain the reasons for using each prescription, but in‐ stead stated that the physician should "just use it in exemplar cases." In this way, Todo Yoshimasu clarified the actions of the prescriptions by analyzing the kind of case in which it should be used.

Yoshimasu then began to collect the herbal drugs to be used in prescriptions. He gathered descriptions of the prescriptions containing each herbal drug from Shokan-zatsubyo-ron and discussed the effects of each herbal drug based on commonalities in the properties of prescriptions containing the drug. In other words, common symptoms referenced in the de‐ scriptions of the prescriptions were regarded as related to the herbal drug that was common to the prescriptions. He learned about the efficacy of each of the herbal drugs from Shokanzatsubyo-ron by comparing it with his clinical experience. Such knowledge was collected in Yaku-cho ("Properties of Herbal Drugs").

For example, the action of the herbal drug licorice is discussed as follows: Although licorice (root with stolon of *Glycyrrhiza uralensis* Fisch. or *G. glabra* L.) is included in many prescrip‐ tions, prescriptions containing a particularly large quantity of licorice are shakuyaku-kanzoto ("peony and licorice combination"), kanzo-kankyo-to ("licorice and ginger combination"), kanzo-shashin-to ("pinellia and licorice combination"), and kan-baku-taiso-to ("licorice and jujube combination"). Based on the cases described in the literature that involved use of these prescriptions and on comparisons with his own clinical experience, he concluded that licorice suppressed various otherwise imminent symptoms.

He next listed the effects of each prescription based on the actions of the constituent crude drugs he had examined. These findings are summarized in the book Ho-kyoku ("The Ulti‐ mate Properties of the Prescriptions").

For example, the keishi-to ("cinnamon combination") prescription, which is composed of cinnamon (bark of *Cinnamomum cassia* Blume), peony (root of *Paeonia lactiflora* Pall.), licorice, jujube (fruit of *Zizyphus jujuba* Mill. var. *inermis* Rehd.), and ginger (rhizome of *Zingiber offi‐ cinalis* Rosc.), is used for patients with some upward streams such as hot flashes, headaches, fevers, sweats, and dislike of wind (feeling sick when exposed to wind). According to Yoshi‐ masu, keishi-ka-kakkon-to ("cinnamon and pueraria combination"), formed by adding pu‐ eraria (root of *Pueraria lobata* Ohwi), should be used for patients with keishi-to symptoms in combination with "tension from the nape to the back," which indicated that pueraria should be added.

than is Korean ginseng (ninjin in Japanese, root of *P. ginseng* C. A. Meyer, *ren-shen* in Chinese) for stomach diseases accompanied by an epigastric obstruction (shin-ka-hi, *Xin-xia-pi* in Chinese). Thus, TJM and TCM both use *P. ginseng* root as a nourishing

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**2.** (Fig. 3c) To-ki: Root of *Angelica acutiloba* Kitagawa (or *A. acutiloba* Kitagawa var. *sugiya‐ mae*, family Umbelliferae) is used as To-ki (for soothing pain, corresponding to dong-

**3.** (Fig. 3d) Sen-kyu (Kyu-kyu): Rhizome of *Cnidium officinale* Makino (family Umbellifer‐ ae) is used as sen-kyu (Cnidium rhizome) in Japan (corresponding to *chuan-xiong* in Chinese) for soothing pain and is often used in combination with to-ki. The use of *Ligu‐*

**Figure 3.** Examples of herbal drugs used in traditional Japanese medicine (TJM). (a) chiku-setu-nin-jin (rhizome of Pan‐ *ax japonicus* C. A. Meyer), (b) nin-jin (root of *P. ginseng* C. A. Meyer), (c) to-ki (root of *Angelica acutiloba* Kitagawa), and

**4.** Sai-ko: Root of *Bupleurum falcatum* L. (family Umbelliferae) is used as sai-ko (Bupleu‐ rum root), an antifebrile agent and to regulate liver functions in TJM, whereas *chai-hu*, the root of *B. chinense* DC (and *B. scorzonerifolium* Willd.) is considered a diaphoretic in

**5.** Ko-boku: Magnolia bark is used in both TJM and TCM for distension from the chest to the stomach that is due to a digestive organ disorder, which is often accompanied by

(d) sen-kyu (rhizome of *Cnidium officinale* Makino)

TCM.

gui in Chinese) in TJM, whereas the root of *A. sinensis* Diels is used in TCM.

*sticum chuangxiong* (family Umbelliferae) originated in TCM.

tonic.

Another example is seen in the addition of peony (i.e., an increase in the amount of peony in keishi-to) to form keishi-ka-shakuyaku-to ("cinnamon and peony combination"). If the pa‐ tient exhibited intense convulsions of the rectus abdominis in addition to the symptoms of keishi-to, a prescription with an excess amount of peony was used, as per Ho-kyoku.

In summary, Yoshimasu reorganized descriptions of the efficacy of prescriptions using the following analytical procedures:


This simplification by Yoshimasu was quite useful for understanding the uses of herbal pre‐ scriptions in TJM today and also for clarifying the pharmacological properties of the herbal drugs constituting the prescriptions. Based on this simplification, herbal drugs can be linked to modern analyses of Oriental medicine to understand drug actions in ways that are analo‐ gous to those that enable understanding of Western medicine.

However, such a simplification ignores the notion that an illness should be understood in terms of sequential stages or states of the patient. Considering that, physicians of the Secchu (compromising) School, including Sohaku Asada (1815–1894), avoided extreme simplifica‐ tion and proposed that the good points of the theories underpinning both the Koho and the Gosei-ho should be used. The current major trend in TJM is based on his efforts.

## **5. Differences in herbal drugs used in TJM and TCM**

The two forms of herbal medicine differ with respect to prescriptions and crude drugs. Many herbal drugs used in TCM are also used in TJM. However, it had been difficult to im‐ port herbal products from China to Japan during the Edo era because of the Japanese nation‐ al policy of isolation. During this era, Japanese herbalists searched for plant materials that could act as alternatives to Chinese materials. Thus, the following are examples of differen‐ ces between the plant materials used in TCM and TJM [6].

**1.** (Fig. 3a and b) Nin-jin: Japanese ginseng (chiku-setsu-nin-jin in Japanese, rhizome of *Panax japonicus* C. A. Meyer, family Araliaceae) used in TJM is much more effective than is Korean ginseng (ninjin in Japanese, root of *P. ginseng* C. A. Meyer, *ren-shen* in Chinese) for stomach diseases accompanied by an epigastric obstruction (shin-ka-hi, *Xin-xia-pi* in Chinese). Thus, TJM and TCM both use *P. ginseng* root as a nourishing tonic.

jujube (fruit of *Zizyphus jujuba* Mill. var. *inermis* Rehd.), and ginger (rhizome of *Zingiber offi‐ cinalis* Rosc.), is used for patients with some upward streams such as hot flashes, headaches, fevers, sweats, and dislike of wind (feeling sick when exposed to wind). According to Yoshi‐ masu, keishi-ka-kakkon-to ("cinnamon and pueraria combination"), formed by adding pu‐ eraria (root of *Pueraria lobata* Ohwi), should be used for patients with keishi-to symptoms in combination with "tension from the nape to the back," which indicated that pueraria should

Another example is seen in the addition of peony (i.e., an increase in the amount of peony in keishi-to) to form keishi-ka-shakuyaku-to ("cinnamon and peony combination"). If the pa‐ tient exhibited intense convulsions of the rectus abdominis in addition to the symptoms of

In summary, Yoshimasu reorganized descriptions of the efficacy of prescriptions using the

**2.** Clarifying the efficacy of the respective herbal drugs based on the uses of the prescrip‐

**3.** Identifying the effectiveness of prescriptions based on the efficacy of the constituent

This simplification by Yoshimasu was quite useful for understanding the uses of herbal pre‐ scriptions in TJM today and also for clarifying the pharmacological properties of the herbal drugs constituting the prescriptions. Based on this simplification, herbal drugs can be linked to modern analyses of Oriental medicine to understand drug actions in ways that are analo‐

However, such a simplification ignores the notion that an illness should be understood in terms of sequential stages or states of the patient. Considering that, physicians of the Secchu (compromising) School, including Sohaku Asada (1815–1894), avoided extreme simplifica‐ tion and proposed that the good points of the theories underpinning both the Koho and the

The two forms of herbal medicine differ with respect to prescriptions and crude drugs. Many herbal drugs used in TCM are also used in TJM. However, it had been difficult to im‐ port herbal products from China to Japan during the Edo era because of the Japanese nation‐ al policy of isolation. During this era, Japanese herbalists searched for plant materials that could act as alternatives to Chinese materials. Thus, the following are examples of differen‐

**1.** (Fig. 3a and b) Nin-jin: Japanese ginseng (chiku-setsu-nin-jin in Japanese, rhizome of *Panax japonicus* C. A. Meyer, family Araliaceae) used in TJM is much more effective

Gosei-ho should be used. The current major trend in TJM is based on his efforts.

keishi-to, a prescription with an excess amount of peony was used, as per Ho-kyoku.

**1.** Collecting information on the uses of prescriptions from Shokan-zatsubyo-ron.

be added.

54 Alternative Medicine

following analytical procedures:

herbal drugs.

tions containing those herbal drugs.

gous to those that enable understanding of Western medicine.

**5. Differences in herbal drugs used in TJM and TCM**

ces between the plant materials used in TCM and TJM [6].


**Figure 3.** Examples of herbal drugs used in traditional Japanese medicine (TJM). (a) chiku-setu-nin-jin (rhizome of Pan‐ *ax japonicus* C. A. Meyer), (b) nin-jin (root of *P. ginseng* C. A. Meyer), (c) to-ki (root of *Angelica acutiloba* Kitagawa), and (d) sen-kyu (rhizome of *Cnidium officinale* Makino)


pain, and also for relief of bronchitis. The bark of *Magnolia obovata* Thunb. (family Mag‐ noliaceae), regarded as wa-ko-boku (Japanese Magonolia bark), is different from the Chinese preparation (*hou-po* in Chinese) from *M. officinalis* Rehd. et Wils. and *M. offici‐ nalis* var. *biloba* Rehd. et Wills. In this case, Yoshimasu preferred the Chinese version.

**6.1. Tannins and related compounds: Major constituents of Japanese folk medicines or**

Hydrolyzable tannins are esters of galloyl and related polyphenolic acyl groups with glu‐ cose or some other sugars/polyalcohols. Although various types of hydrolyzable tannins have been found in plants, geraniin (**1**) is a representative one among them [7]. One of the most important herbal drugs in Japan is the geranium herb, the overground parts of *G. thun‐ bergii*. The main constituent is crystalline tannin geraniin (**1**), and the structure containing a dehydrohexahydroxydiphenoyl group (**1'**) was reported in 1977 [8]. Although this com‐ pound equilibrates in a mixture, the structural factor forming the mixture was not clarified

that it forms a mixture of six-membered (**1a**) and five-membered hemi-ketal structures (**1b**) (Fig. 4) [9]. An X-ray analysis of crystalline geraniin revealed the **1a** form with seven mole‐

**Figure 4.** Structure of geraniin (**1**) forming an equilibrium mixture of six-membered hemi-ketal (**1a**) and five-mem‐

Further examination of this source plant revealed the presence of the co-existing hydro‐ lyzable tannins furosin; didehydrogeraniin; furosinin [11]; geraniinic acids B and C; phyl‐ lunthusiins B, C, E, and F [12]; and acalyphidin M1 [13]. However, several compounds are formed after linking with ascorbic acid in the plant; these include ascorgeraniin (= elaeocarpusin) (**2**) [14,15] and furosonin (**3**) [13] (Fig. 5). We also found that geraniin is

bered hemi-ketal (**1b**) forms. Structure **1** was assigned to geraniin, firstly.

H and 13C nuclear magnetic resonance spectra revealed

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57

*6.1.1. Hydrolyzable tannins of Geranium thunbergii*

at that time. Detailed analysis with 1

cules of water [10].

**TJM**


These differences should be understood when these herbal drugs are used clinically and studied in research settings.

## **6. Constituents of herbal drugs used in TJM**

This section discusses studies on the constituents of the herbal drugs that are used in TJM and in our laboratory. Yoshimasu's work on the practical aspects of herbal drugs is quite useful for researchers attempting to understand the uses of herbal drugs in TJM, and the re‐ searchers in our laboratory are searching for new constituents based on such materials rath‐ er than considering the implications of the complex theories underlying TCM.

#### **6.1. Tannins and related compounds: Major constituents of Japanese folk medicines or TJM**

#### *6.1.1. Hydrolyzable tannins of Geranium thunbergii*

pain, and also for relief of bronchitis. The bark of *Magnolia obovata* Thunb. (family Mag‐ noliaceae), regarded as wa-ko-boku (Japanese Magonolia bark), is different from the Chinese preparation (*hou-po* in Chinese) from *M. officinalis* Rehd. et Wils. and *M. offici‐ nalis* var. *biloba* Rehd. et Wills. In this case, Yoshimasu preferred the Chinese version.

**6.** Byaku-jutsu: Rhizomes from the following *Atractylodes* species are used for dyspepsia. That derived from *Atractylodes japonica* Koidz. ex Kitam. (family Compositae) is regard‐ ed as wa-byaku-jutsu (Japanese Atractylodes rhizome). In contrast, kara-byaku-jutsu (Chinese Atractylodes rhizome, *bai-zhu* in Chinese) is derived from *A. macrocephala*

**7.** O-ren: Rhizome derived from the following *Coptis* species is used to eliminate fever of the upper body, particularly in the heart. *Coptis japonica* Makino (family Ranunculaceae) is cultivated in Japan, and its rhizome, particularly that from Ishikawa Prefecture has been used since the Edo era. In contrast, Chinese products, used in both in China (*huang-lian* in Cinese) and Japan, are derived from *C. chinensis* Franchet, *C. deltoidea* C.

**8.** San-sho: Fruit of *Zanthoxylum piperitum* DC. (family Rutaceae) is known as "Japanese pepper," and its peel is used for dyspepsia in TJM. *Z. bugeanum* Maxim. or *Z. simulans* Hance are the source plants of Sichuan pepper (*hua-jiao* or *chuan-jiao* in Chinese), and they are used in analogous ways in TCM. However, they are not used for medicinal

**9.** Bo-fu: Root (including rhizome) of *Saposhnikovia divaricata* Schischk. (family Umbellifer‐ ae) is used for fever, pain, and spasms in TJM and TCM (*fang-feng* in Chinese). The root (with rhizome) of *Glehnia littoralis* Fr. Scmidt ex Miq. (family Umbelliferae) was devel‐ oped as a subsitute for bo-fu in Japan and is called hama-bo-fu in Japanese. In contrast,

**10.** In-chin-ko: Spike composed of many minor flowers of *Artemisia capillaris* Thunb. (family Compositae) is used for thirst and jaundice in TJM, whereas young shoots of this plant

These differences should be understood when these herbal drugs are used clinically and

This section discusses studies on the constituents of the herbal drugs that are used in TJM and in our laboratory. Yoshimasu's work on the practical aspects of herbal drugs is quite useful for researchers attempting to understand the uses of herbal drugs in TJM, and the re‐ searchers in our laboratory are searching for new constituents based on such materials rath‐

*G. littoralis* is regarded as *bei-sha-shen* in China, and the root is used for coughs.

are used for the same purpose under the name of *yin-chen* in China.

er than considering the implications of the complex theories underlying TCM.

**6. Constituents of herbal drugs used in TJM**

Koidz. (=*A. ovata* DC.). The latter is used in both China and Japan.

Y. Cheng, and *C. teeta* Wallich.

purpose in Japan.

56 Alternative Medicine

studied in research settings.

Hydrolyzable tannins are esters of galloyl and related polyphenolic acyl groups with glu‐ cose or some other sugars/polyalcohols. Although various types of hydrolyzable tannins have been found in plants, geraniin (**1**) is a representative one among them [7]. One of the most important herbal drugs in Japan is the geranium herb, the overground parts of *G. thun‐ bergii*. The main constituent is crystalline tannin geraniin (**1**), and the structure containing a dehydrohexahydroxydiphenoyl group (**1'**) was reported in 1977 [8]. Although this com‐ pound equilibrates in a mixture, the structural factor forming the mixture was not clarified at that time. Detailed analysis with 1 H and 13C nuclear magnetic resonance spectra revealed that it forms a mixture of six-membered (**1a**) and five-membered hemi-ketal structures (**1b**) (Fig. 4) [9]. An X-ray analysis of crystalline geraniin revealed the **1a** form with seven mole‐ cules of water [10].

**Figure 4.** Structure of geraniin (**1**) forming an equilibrium mixture of six-membered hemi-ketal (**1a**) and five-mem‐ bered hemi-ketal (**1b**) forms. Structure **1** was assigned to geraniin, firstly.

Further examination of this source plant revealed the presence of the co-existing hydro‐ lyzable tannins furosin; didehydrogeraniin; furosinin [11]; geraniinic acids B and C; phyl‐ lunthusiins B, C, E, and F [12]; and acalyphidin M1 [13]. However, several compounds are formed after linking with ascorbic acid in the plant; these include ascorgeraniin (= elaeocarpusin) (**2**) [14,15] and furosonin (**3**) [13] (Fig. 5). We also found that geraniin is easily converted to corilagin (**4**) and repandusinic acid A (**5**) (Fig. 5) under near physio‐ logical conditions (pH 7.4) [13].

*6.1.2. Proanthocyanidins of Saxifraga stolonifera*

*Saxifraga stolonifera* Curtis (family Saxifragaceae) is used as an ethnic medicine in Japan and China. A study of the constituents of this plant revealed that the major polyphenolic constit‐ uents of the overground part are proanthocyanidins, which are highly galloylated at O-3 of the respective flavan [(-)-epicatechin unit] in addition to 11-*O*-galloylbergenin (7) [20,21]. An oligomeric proanthocyanidin fraction, Ss-tannin-1 (8), with a molecular weight of 2300 shows potent antioxidant effects on lipid peroxidation in rat mitochondria induced by ade‐ nosine diphosphate (ADP) and ascorbic acid, and on that in rat microsomes induced by ADP and nicotinamide adenine dinucleotide phosphate [21]. Among the isolated constitu‐ ents from this plant (Fig. 6), the administration of 3-*O*-galloylepicatechin-(4β→8)- 3-*O*-gal‐ loylepicatechin (**9**) and 3-*O*-galloylepicatechin-(4β→6)-3-*O*-galloylepicatechin (**10**) results in

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a noticeable increase in the life span of mice after inoculation of Sarcoma-180 [22].

**Figure 6.** Structures of proanthocyanidins obtained from *Saxifraga stolonifera*.

Because some hydrolyzable tannins show noticeable effects on β-lactam resistance of methi‐ cillin-resistant *Staphylococcus aureus* (MRSA) [16-18], we examined the effects of several available tannins, and repandusinic acid A and corilagin showed a noticeable suppressive effect on oxacillin resistance of MRSA [13].

The presence of tannins with analogous structures including mallotusinic acid (**6**) in *Mallo‐ tus japonicus* is shown in Fig. 5 [8,19].

**Figure 5.** Tannins structurally related to geraniin. Compound 6 was isolated from *M. japonicus*.

#### *6.1.2. Proanthocyanidins of Saxifraga stolonifera*

easily converted to corilagin (**4**) and repandusinic acid A (**5**) (Fig. 5) under near physio‐

Because some hydrolyzable tannins show noticeable effects on β-lactam resistance of methi‐ cillin-resistant *Staphylococcus aureus* (MRSA) [16-18], we examined the effects of several available tannins, and repandusinic acid A and corilagin showed a noticeable suppressive

The presence of tannins with analogous structures including mallotusinic acid (**6**) in *Mallo‐*

**Figure 5.** Tannins structurally related to geraniin. Compound 6 was isolated from *M. japonicus*.

logical conditions (pH 7.4) [13].

58 Alternative Medicine

effect on oxacillin resistance of MRSA [13].

*tus japonicus* is shown in Fig. 5 [8,19].

*Saxifraga stolonifera* Curtis (family Saxifragaceae) is used as an ethnic medicine in Japan and China. A study of the constituents of this plant revealed that the major polyphenolic constit‐ uents of the overground part are proanthocyanidins, which are highly galloylated at O-3 of the respective flavan [(-)-epicatechin unit] in addition to 11-*O*-galloylbergenin (7) [20,21]. An oligomeric proanthocyanidin fraction, Ss-tannin-1 (8), with a molecular weight of 2300 shows potent antioxidant effects on lipid peroxidation in rat mitochondria induced by ade‐ nosine diphosphate (ADP) and ascorbic acid, and on that in rat microsomes induced by ADP and nicotinamide adenine dinucleotide phosphate [21]. Among the isolated constitu‐ ents from this plant (Fig. 6), the administration of 3-*O*-galloylepicatechin-(4β→8)- 3-*O*-gal‐ loylepicatechin (**9**) and 3-*O*-galloylepicatechin-(4β→6)-3-*O*-galloylepicatechin (**10**) results in a noticeable increase in the life span of mice after inoculation of Sarcoma-180 [22].

**Figure 6.** Structures of proanthocyanidins obtained from *Saxifraga stolonifera*.

### **6.2. Polyphenolics in herbal drugs used in TCM and TJM**

#### *6.2.1. Caffeic acid derivatives of Artemisia leaf and Perilla herb*

The leaves of *Artemisia princeps* Pamp. or *A. montana* Pamp. (family Compositae) are used as gai-yo to stop bleeding and blood circulation difficulties in Japan, and the corresponding *A. argyi* Levl. et Vant. is used as *ai-ye* in China. Investigations of the constituents of the leaf re‐ vealed that dicaffeoylquinic acids [particularly 3,5-di-*O*-caffeoylquinic acid (**11**)] are the ma‐ jor constituents of *A. princeps* and *A. montana* [23] (Fig. 7).

*6.2.2. Flavonoids and 3-arylcoumarins from licorice*

tance of flavonoids and related phenolics [27].

the cytomegalovirus promoter [31].

Licorice, the root (with stolon) of *Glycyrrhiza uralensis* and *G. glabra*, is widely applied in var‐ ious TCM and TJM prescriptions. Although glychyrrhizin and related triterpene glycosides are regarded as the major constituents, Japanese researchers have reported on the impor‐

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Our investigation of licorice constituents revealed the inhibitory effects of flavonoids, in‐ cluding new ones, on xanthine oxidase [28] and monoamine oxidase [29]. Several also effec‐ tive against the cytopathic effects of human immunodeficiency virus (HIV). The inhibitory effects of those constituents on giant cell formation induced by HIV were constituents are examined using a cell line sensitive to the cytopathic activity of HIV. Licochalcone A (**13**), isolicoflavonol (**14**), glycycoumarin (**15**), glycyrrhisoflavone (**16**), and licopyranocoumarin (**17**) inhibited at a 1:25 concentration (20 μg/ml) relative to that of glychyrrhiziin showed an analogous effect (500 μg/ml) (Fig. 8) [30]. Further investigation revealed that the HIV pro‐ moter activity induced by 12-O-tetradecanoylphorbol-13-*O*-acetate is suppressed by licorice phenolics. Those including glycycoumarin, and tetrahydroxymethocychalcone showed a specific suppressive effect on the HIV promoter; this effect was in contrast to its effects on

**Figure 8.** Structures of licorice phenolics that suppress human immunodeficiency virus (HIV) cytopathic effects.

**Figure 7.** Structures of caffeic acid derivatives found in Artemisia leaf and Perilla herb

The aboveground part of *Perilla frutescens* Brit. var. *acuta* Kudo (or *P. frutescens* Brit. var. *crispa* Decne., family Labiatae) is used as so-yo or shi-so-yo for regulating energy flow or treating bronchial asthma and bronchitis in TJM and is used in analogous ways in TCM un‐ der the name *zi-su-ye*. Our study on the leaf constituents revealed that rosmarinic acid (an ester of caffeic acid with 3,4-dihydroxyphenyllactic acid, **12**) is a major constituent and showed that instability during the drying process of the leaves should be considered when using this herbal drug [24] (Fig. 7).

Caffeoylquinic acids show inhibitory effects on histamine release from rat peritoneal mast cells [25,26] and also on the formation of leukotriene B4 (LTB4) in human polymorphonu‐ clear leukocytes (PMN-L). Rosmarinic acid shows a strong inhibitory effect on the formation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and LTB4 in PMN-L [25]. Because arachidonate metabolism is related to allergic inflammation and asthma, these results suggest that the ef‐ fects of these constituents may participate in the actions of the herbal drugs containing them.

#### *6.2.2. Flavonoids and 3-arylcoumarins from licorice*

**6.2. Polyphenolics in herbal drugs used in TCM and TJM**

60 Alternative Medicine

*6.2.1. Caffeic acid derivatives of Artemisia leaf and Perilla herb*

jor constituents of *A. princeps* and *A. montana* [23] (Fig. 7).

**Figure 7.** Structures of caffeic acid derivatives found in Artemisia leaf and Perilla herb

using this herbal drug [24] (Fig. 7).

them.

The aboveground part of *Perilla frutescens* Brit. var. *acuta* Kudo (or *P. frutescens* Brit. var. *crispa* Decne., family Labiatae) is used as so-yo or shi-so-yo for regulating energy flow or treating bronchial asthma and bronchitis in TJM and is used in analogous ways in TCM un‐ der the name *zi-su-ye*. Our study on the leaf constituents revealed that rosmarinic acid (an ester of caffeic acid with 3,4-dihydroxyphenyllactic acid, **12**) is a major constituent and showed that instability during the drying process of the leaves should be considered when

Caffeoylquinic acids show inhibitory effects on histamine release from rat peritoneal mast cells [25,26] and also on the formation of leukotriene B4 (LTB4) in human polymorphonu‐ clear leukocytes (PMN-L). Rosmarinic acid shows a strong inhibitory effect on the formation of 5-hydroxy-6,8,11,14-eicosatetraenoic acid and LTB4 in PMN-L [25]. Because arachidonate metabolism is related to allergic inflammation and asthma, these results suggest that the ef‐ fects of these constituents may participate in the actions of the herbal drugs containing

The leaves of *Artemisia princeps* Pamp. or *A. montana* Pamp. (family Compositae) are used as gai-yo to stop bleeding and blood circulation difficulties in Japan, and the corresponding *A. argyi* Levl. et Vant. is used as *ai-ye* in China. Investigations of the constituents of the leaf re‐ vealed that dicaffeoylquinic acids [particularly 3,5-di-*O*-caffeoylquinic acid (**11**)] are the ma‐ Licorice, the root (with stolon) of *Glycyrrhiza uralensis* and *G. glabra*, is widely applied in var‐ ious TCM and TJM prescriptions. Although glychyrrhizin and related triterpene glycosides are regarded as the major constituents, Japanese researchers have reported on the impor‐ tance of flavonoids and related phenolics [27].

Our investigation of licorice constituents revealed the inhibitory effects of flavonoids, in‐ cluding new ones, on xanthine oxidase [28] and monoamine oxidase [29]. Several also effec‐ tive against the cytopathic effects of human immunodeficiency virus (HIV). The inhibitory effects of those constituents on giant cell formation induced by HIV were constituents are examined using a cell line sensitive to the cytopathic activity of HIV. Licochalcone A (**13**), isolicoflavonol (**14**), glycycoumarin (**15**), glycyrrhisoflavone (**16**), and licopyranocoumarin (**17**) inhibited at a 1:25 concentration (20 μg/ml) relative to that of glychyrrhiziin showed an analogous effect (500 μg/ml) (Fig. 8) [30]. Further investigation revealed that the HIV pro‐ moter activity induced by 12-O-tetradecanoylphorbol-13-*O*-acetate is suppressed by licorice phenolics. Those including glycycoumarin, and tetrahydroxymethocychalcone showed a specific suppressive effect on the HIV promoter; this effect was in contrast to its effects on the cytomegalovirus promoter [31].

**Figure 8.** Structures of licorice phenolics that suppress human immunodeficiency virus (HIV) cytopathic effects.

**6.3. Ameliorating effect of extracts from Polygala root and Uncaria hook on scopolamine-**

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It is very important to develop new drugs for the treatment of patients with dementia as the number of individuals with this condition is now rapidly increasing due to the increase in the elderly population. The root of *Polygala enuifolia* Willd. (on-ji in Japanese and *yuan-zhi* in Chinese; family Polygalaceae) is used in TJM and TCM prescriptions for forgetfulness, neu‐ rasthenia, and insomnia. An investigation to identify the constituents of this herbal drug that are effective for impaired spatial cognition was conducted in rats using an eight-arm ra‐ dial maze task. This task is useful for discriminating shshort-term memory from long-term one. The results showed that sinapic acid had the most potent effect among the cinnamic acid derivatives examined. Sinapoyl derivatives such as 3,6'di-*O*-sinapoylsucrose (21) are contained in this plant [33]. Analogous results have been obtained for phenolic constituents, including (+)-catechin of Uncaria hook (stem with hooks of *Uncaria rhynchophylla* Miq., *U. si‐ nensis* Havil., and *U. macrophylla* Wall.; cho-to-ko in Japanese, *gou-teng* in Chinese; family Rubiaceae) [34]. Further studies of the adsorption/metabolism process and the mechanisms

**Figure 10.** Structure of 3',6-di-O-sinapoyl-sucrose contained in *Polygala tenuifolia* root.

Explanations of the pharmacological properties of herbal drugs based on TJM concepts have been useful for identifying new compounds with various structures. These explanations are also useful for understanding the roles of herbal prescriptions and applications in modern medicine. Modern medicine should consider some of the basic concepts of traditional medi‐

**induced impairment of spatial cognition**

are required.

**7. Conclusion**

cine as they may contain wisdom.

**Figure 9.** Licorice phenolics that show the most potent antibacterial effects on methicillin-resistant *Staphylococcus aureus* (MRSA) (compounds **18** and **19**) and noticeable suppressive effects on oxacillin resistance of MRSA.


**Table 2.** Effect of licoricidin on the antibacterial activity of oxacillin.

The effects of licorice phenolics on MRSA were also investigated. Two flavonoids, 8-(γ,γdimethyally)-wighteone (**18**) and 3'-(γ,γ-dimethylallyl)-kievitone (**19**) showed their most potent antibacterial effects at a minimum inhibitory concentration (MIC) of 8 μg/ml. Fur‐ thermore, licoricidin (**20**) induced an effective decrease in oxacillin MIC (Fig. 9, Table 2) [32].

These findings suggest that licorice is a useful herbal source for the development of the pri‐ mary constituents of the compounds used in modern medicine.

#### **6.3. Ameliorating effect of extracts from Polygala root and Uncaria hook on scopolamineinduced impairment of spatial cognition**

It is very important to develop new drugs for the treatment of patients with dementia as the number of individuals with this condition is now rapidly increasing due to the increase in the elderly population. The root of *Polygala enuifolia* Willd. (on-ji in Japanese and *yuan-zhi* in Chinese; family Polygalaceae) is used in TJM and TCM prescriptions for forgetfulness, neu‐ rasthenia, and insomnia. An investigation to identify the constituents of this herbal drug that are effective for impaired spatial cognition was conducted in rats using an eight-arm ra‐ dial maze task. This task is useful for discriminating shshort-term memory from long-term one. The results showed that sinapic acid had the most potent effect among the cinnamic acid derivatives examined. Sinapoyl derivatives such as 3,6'di-*O*-sinapoylsucrose (21) are contained in this plant [33]. Analogous results have been obtained for phenolic constituents, including (+)-catechin of Uncaria hook (stem with hooks of *Uncaria rhynchophylla* Miq., *U. si‐ nensis* Havil., and *U. macrophylla* Wall.; cho-to-ko in Japanese, *gou-teng* in Chinese; family Rubiaceae) [34]. Further studies of the adsorption/metabolism process and the mechanisms are required.

**Figure 10.** Structure of 3',6-di-O-sinapoyl-sucrose contained in *Polygala tenuifolia* root.

## **7. Conclusion**

**Figure 9.** Licorice phenolics that show the most potent antibacterial effects on methicillin-resistant *Staphylococcus*

**Minimum inhibitory concentration (MIC) of oxacillin (μg/ml)**

The effects of licorice phenolics on MRSA were also investigated. Two flavonoids, 8-(γ,γdimethyally)-wighteone (**18**) and 3'-(γ,γ-dimethylallyl)-kievitone (**19**) showed their most potent antibacterial effects at a minimum inhibitory concentration (MIC) of 8 μg/ml. Fur‐ thermore, licoricidin (**20**) induced an effective decrease in oxacillin MIC (Fig. 9, Table 2)

These findings suggest that licorice is a useful herbal source for the development of the pri‐

*aureus* (MRSA) (compounds **18** and **19**) and noticeable suppressive effects on oxacillin resistance of MRSA.

Licoricidin MRSA strains MSSA concentration OM481 OM505 OM584 OM623 209P None 512 64 256 512 <0.5 8 μg/ml <0.5 <0.5 <0.5 <0.5 <0.5 4 μg/ml 16 8 16 16 <0.5

**Table 2.** Effect of licoricidin on the antibacterial activity of oxacillin.

mary constituents of the compounds used in modern medicine.

[32].

62 Alternative Medicine

Explanations of the pharmacological properties of herbal drugs based on TJM concepts have been useful for identifying new compounds with various structures. These explanations are also useful for understanding the roles of herbal prescriptions and applications in modern medicine. Modern medicine should consider some of the basic concepts of traditional medi‐ cine as they may contain wisdom.

## **Author details**

#### Tsutomu Hatano

Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Tsushima-naka, Kita-ku, Okayama, Japan

[12] Ito H, Hatano T, Namba O, Shirono T, Okuda T, Yoshida T. Constituents of *Geranium thunbergii* Sieb. et Zucc. XV. Modified Dehydroellagitannins, Geraniinic Acids B and C, and Phyllanthusiin F. Chemical and Pharmaceutical Bulletin 1999; 47 1148-1151.

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65

[13] Taniguchi S, Nogaki R, Bao LM, Kuroda T, Ito H, Hatano T. Furosonin, a Novel Hy‐ drolyzable Tannin from *Geranium thunbergii*. Heterocycles, published on line. DOI:

[14] Okuda T, Yoshida T, Hatano T, Ikeda Y. Biomimetic Synthesis of Elaeocarpusin. Het‐

[15] Nonaka G, Morimoto S, Nishioka I. Elaeocarpusin, a Proto-type of Geraniin from *Geranium thunbergii*. Chemical and Pharmaceutical Bulletin 1986; 34 941-943.

[16] Shiota S, Shimizu M, Mizusima T, Ito H, Hatano T, Yoshida T, Tsuchiya T. Restora‐ tion of Effectiveness of beta-Lactams on Methicillin-resistant *Staphylococcus aureus* by Tellimagrandin I from Rose Red. FEMS Microbiology Letters 2000; 185 135-138.

[17] Shimizu M, Shiota S, Mizushima T, Ito H, Hatano T, Yoshida T, Tsuchiya T. Marked Potentiation of Activity of beta-Lactams against Methicillin-resistant *Staphylococcus aureus* by Corilagin. Antimicrobial Agents and Chemotherapy 2001; 45 3198-3201.

[18] Shiota S, Shimizu M, Sugiyama J, Morita Y, Mizushima T, Tsuchiya T. Mechanisms of Action of Corilagin and Tellimagrandin I That Remarkably Potentiate the Activity of beta-Lactams against Methicillin-resistant *Staphylococcus aureus*. Microbiology and

[19] Saijo R, Nonaka G, Nishioka I. Tannins and Related Compounds. LXXXIV. Isolation and Characterization of Five New Hydrolyzable Tannins from the Bark of *Mallotus*

[20] Okuda T, Kimura Y, Yoshida T, Hatano T, Okuda H, Archi S. Studies on the Activi‐ ties of Tannins and Related Compounds from Medicinal Plants and Drugs. I. Inhibi‐ tory Effects on Lipid Peroxidation in Mitochondria and Microsomes of Liver.

[21] Hatano T, Urita K, Okuda T. Tannins and Related Constituents of *Saxifraga stolonifela.* Journal of Medical and Pharmaceutical Society for Wakan-Yaku 1986; 3 434-435 (in

[22] Miyamoto K, Kishi N, Koshiura R, Yoshida T, Hatano T, Okuda T. Relationship be‐ tween the Structures and the Antitumor Activities of Tannins. Chemical and Phar‐

[23] Okuda T, Hatano T, Agata I, Nishibe S, Kimura K. Tannins in *Artemisia montana*, *A. princeps* and Related Species of Plant. Yakugaku Zasshi 1986; 106 894-899 (in Japa‐

*japonicus*. Chemical and Pharmaceutical Bulletin 1989; 37 2063-2070.

Chemical and Pharmaceutical Bulletin 1983; 31 1625-1631.

10.3987/COM-12-S(N)65.

erocycles 1986; 24 1841-1843.

Immunology 2004;48 67-73.

maceutical Bulletin 1987; 35 814-832.

Japanese).

nese).

## **References**


[12] Ito H, Hatano T, Namba O, Shirono T, Okuda T, Yoshida T. Constituents of *Geranium thunbergii* Sieb. et Zucc. XV. Modified Dehydroellagitannins, Geraniinic Acids B and C, and Phyllanthusiin F. Chemical and Pharmaceutical Bulletin 1999; 47 1148-1151.

**Author details**

64 Alternative Medicine

Tsutomu Hatano

**References**

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[7] Haslam E. Plant Polyphenols: Vegetable Tannins Revisited. Cambridge: Cambridge

[8] Okuda T, Yoshida T, Naeshiro H. Constituents of *Geranium thunbergii* SIieb. et Zucc. IV. Ellagitannins. (2). Structure of Geraniin. Chemical and Pharmaceutical Bulletin

[9] Okuda T, Yoshida T, Hatano T. Constituents of *Geranium thunbergii* Sieb. et Zucc. Part 12. Hydrated Stereostructure and Equilibration of Geraniin. Journal of the

[10] Luger P, Weber M, Kashino S, Amakura Y, Yoshida T, Okuda T, Beurskensd G, Dauter Z. Structure of the Tannin Geraniin Based on Conventional X-ray Data at 295 K and on Synchrotron Data at 293 and 120 K. Acta Crystllographica 1998; B54

[11] Yazaki K, Hatano T, Okuda T. Constituents of *Geranium thunbergii* Sieb. et Zucc. Part 14. Structures of Didehydrogeraniin, Furosinin, and Furosin. Journal of the Chemical

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**Chapter 4**

**Phytochemicals of the Chinese Herbal Medicine**

The family Taccaceae is composed of two genera, *Tacca* and *Schizocapsa*, and about 10 spe‐ cies, with most distributed in tropical regions of Asia, the Pacific Islands, and Australia [1]. *Tacca chantrieri* André is a perennial plant that occurs in the southeast region of mainland China, and its rhizomes have been used for the treatment of gastric ulcers, enteritis, and hepatitis in Chinese folk medicine. According to a Chinese herbal dictionary, *T. plantaginea* has also been used for the same purposes as *T. chantrieri* [2]. The chemical constituents of *T. plantaginea* have been extensively examined and a series of highly oxygenated pentacyclic steroids named taccalonolids, which have a γ-enol lactone, have been isolated as characteris‐ tic components of the herb [3], but there has been only one report of the secondary metabo‐ lites of *T. chantrieri*, in which a few trivial sterols such as stigmasterol and daucusterol, and a diosgenin glycoside were found [4]. Therefore, we focused our attention on the constituents of *T. chantrieri* rhizomes, and a detailed phytochemical investigation of this herbal medicine

In this chapter, we describe the phytochemicals isolated from *T. chantrieri* rhizomes and

*T. chantrieri* specimens were collected in Yunnan Province, People's Republic of China. The rhizomes of *T. chantrieri* (fresh weight, 7.3 kg) were extracted with hot MeOH (3 L × 2). The MeOH extract was concentrated under reduced pressure, and the extract was passed through a polystyrene resin (Diaion HP-20) column eluted with MeOH/H2O gradients,

and reproduction in any medium, provided the original work is properly cited.

© 2012 Yokosuka and Mimaki; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

their biological activities with a focus on cytotoxicity against human cancer cells.

**2. Isolation and structural determination**

*Tacca chantrieri* **Rhizomes**

http://dx.doi.org/10.5772/53668

**1. Introduction**

has been carried out.

Akihito Yokosuka and Yoshihiro Mimaki

Additional information is available at the end of the chapter

