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Data mining and frequency analysis for licorice as a "two-face" herb in Chinese formulae based on Chinese formulae database.

ABSTRACT

Liquorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L., Leguminosae. Licorice is described as 'National Venerable Master' in Chinese medicine and plays paradoxical roles, i.e. detoxification/strengthen efficacy and inducing/enhancing toxicity. Therefore, licorice was called "Two-Face" herb in this paper. The aim of this study is to discuss the paradoxical roles and the perspective usage of this "Two-Face" herb using data mining and frequency analysis.

More than 96,000 prescriptions from Chinese Formulae Database were selected. The frequency and the prescription patterns were analyzed using Microsoft SQL Server 2000. Data mining methods (frequent itemsets) were used to analyze the regular patterns and compatibility laws of the constituent herbs in the selected prescriptions.

The result showed that licorice (Radix glycyrrhizae) was the most frequently used herb in Chinese Formulae Database, other frequently used herbs including Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), etc. Toxic herbs such as Radix aconiti lateralis praeparata (Fu zi), Rhizoma pinelliae (Ban xia) and Cinnabaris (Zhu sha) are top 3 herbs that most frequently used in combination with licorice. Radix et rhizoma ginseng (Ren shen), Poria (Fu ling), Radix Angelicae Sinensis (Dang gui) are top 3 nontoxic herbs that most frequently used in combination with licorice. Moreover, Licorice was seldom used with sargassum (Hai Zao), Herba Cirsii Japonici (Da Ji), Euphorbia kansui (Gan Sui) and Flos genkwa (Yuan Hua), which proved the description of contradictory effect of Radix glycyrrhizae and these herbs as recorded in Chinese medicine theory.

This study showed the principle pattern of Chinese herbal drugs used in combination with licorice or not. The principle patterns and special compatibility laws reported here could be useful and instructive for scientific usage of licorice in clinic application. Further pharmacological and chemical researches are needed to evaluate the efficacy and the combination pattern of these Chinese herbs. The mechanism of the combination pattern of these prescriptions should also be investigated whether additive, synergistic or antagonistic effect exist using in vitro or in vivo models.

Keywords:

Data mining

Licorice

Chinese Formulae Database

Introduction

Formulae are prescription combinations of plant species/ minerals used by practitioners of traditional Chinese medicine (TCM) to enhance therapeutic efficacy and reduce adverse effects based on clinical experience. Nearly 100,000 formulae have been recorded in Chinese Formulae books such as "Ben cao gang mu", etc. (Wang et al. 2008). The possible beneficial effects of some formulae such as Realgar-Indigo naturalis formula (RIF) (Chen et al. 2011; Liu et al. 2012a; Wang et al. 2008) and Fluang Qin Tang has been elucidated with current biomedical approaches (Farrell and Kummar 2003; Fledigan 2010; Kummar et al. 2011; Lam et al. 2010; Liu and Cheng 2012; Villanueva 2010; Wang et al. 2011).

Huang Qin Tang is a Chinese Formula that has been used since 1800 years ago. Huang Qin Tang was used to treat gastrointestinal symptoms such as diarrhea, nausea and vomiting. Recently, Huang Qin Tang is in clinical trials as PHY906 to evaluate its effect as an adjuvant to chemotherapy in metastatic colorectal carcinoma (CRC) (Hedigan 2010; Lam et al. 2010; Villanueva 2010). Huang Qin Tang was composed of four herbs: Scutellaria baicalensis Geori, Glycyrrhiza uralensis Fisch, Paeonia lactiflora Pall, and Ziziphus jujuba Mill, in which Glycyrrhiza uralensis Fisch (Licorice, GANCAO) is an important herb and is described as 'the grandfather of herbs' in Chinese medicine (Ody 2000).

Liquorice is the root of Glycyrrhiza uralensis Fisch. or Glycyrrhiza glabra L., Leguminosae. It is a widely used herbal medicine native to southern Europe and parts of Asia as a herbal medicine and natural sweetener. Licorice is now widely cultivated throughout Europe, the Middle East and Asia. The major constituent of licorice, glycyrrhizin (also known as glycyrrhizic acid or glycyrrhizinic acid), is about 50 times sweeter than sucrose (common sugar). In western countries, licorice is mainly used in non-medicinal usage such as soft drinks, herbal teas and tobacco products (Tobacco Documents Online http://tobaccodocuments.org/profiles/licorice.html]. The medicinal potential of licorice needs further investigation and recognition in western countries.

Licorice and its related products were widely used in China and throughout the world according to an analysis on the imported/exported amount of licorice and its related products in 2009. In 2010, the total imported amount of licorice in China is 4,778,000 ton, the total exported amount of licorice from China is 3,376,000 ton. In 2010, Asia is the number 1 area (81.95%) that mostly imported licorice from China followed with Europe (15.51%) and North America (2.54%) (Zhang 2011).

Since 25 CE, licorice has been extensively used by the Chinese to relieve and prevent cough, phlegm, dyspnea, spasms, and pain. It also relieves spasms of the smooth (involuntary) muscles and exhibits a cortisone-like action. In Ayurvedic medicine, licorice has a long history as a common remedy for its expectorant, anti-inflammatory, and laxative properties (Asl and Hosseinzadeh 2008; Blumenthal and Brinckmann 2000; Brown 2001; Onstad 1996; Wang et al. 2013). In Chinese medicine, Licorice was also combined with other herbs in many herbal formulas by harmonize the characteristics of other herbs, alleviate the toxicity of herbs and modulate the taste of herbs due to its sweet flavor. Liquorice is also recorded as 'National Venerable Master' which plays paradoxical roles, i.e. detoxification/strengthen efficacy and inducing/enhancing toxicity. Due to these reasons, licorice is the most important herb and the focus of research in Chinese medicine.

In Chinese Formulae, licorice has two roles. The first role is harmonizing and modifying herbs in a prescription, which means eliminating various toxicities and enhancing pharmacological effects (i.e. attenuating toxicity and strengthening efficacy). In contrary, the second role of licorice is incompatible with some herbs such as Herba CirsiiJaponici (Da Ji), Euphorbia Icansui (Gan Sui) and Flosgenkwa (Yuan Hua) (i.e. inducing and enhancing toxicity).

That is to say, when licorice was used in combination with some toxic herbs such as Radix aconiti lateralis praeparata (Fu zi), Rhizoma pinelliae (Ban xia) and Cinnabaris (Zhu sha), the toxicity of these herbs might be attenuate by licorice. In contrary, when licorice was used in combination with some other herbs such as Herba Cirsii Japonici (Da Ji), Euphorbia kansui (Gan Sui) and Flos genkwa (Yuan Hua). The toxicity of these herbs might be enhanced by licorice. All of these facts showed that licorice plays paradoxical roles in Chinese Formulae.

Data mining and frequency analysis are important tools to discover the relationship and potential association of attributes among huge amounts of data, and provide results that can be used as the basis for forecasting and decision making. Some mining methods have been very successful in studying the combination rules of Chinese medicine. For example, data mining has been successfully used for syndrome differentiation in traditional Chinese medicine; frequency and pattern analysis of Chinese herbal medicine prescriptions for chronic hepatitis, urticaria, menopausal syndrome and in treating and preventing breast cancer recurrence and metastasis, etc. (Chen et al. 2008; Chien et al. 2013; Jiang et al. 2012; Ningthoujam et al. 2012). Therefore, in our study, using data mining tool and strategy, we discuss the paradoxical roles and the perspective usage of licorice as a "Two-Face" herb.

Materials and methods

Data sources and data extraction

Data used in this study was based on Chinese Formulae Database. Chinese Formulae Database contains 96,592 formulae records. Each record represents a single prescription and provides the cited information. The data in this database is derived from 677 Chinese Formulae books (from 200 BC HAN to 1980) such as Zhang Zhongjing's "Treatise on Cold Damage and Miscellaneous Diseases" (Shang Han Za Bing Lun) and Li Shizhen's "The Compendium of Materia Medica" (Ben Cao Gang Mu), the most comprehensive documentation of the use of medicinal herbs, minerals and animal parts.

The list of names of herbs including toxic herbs was chosen from Pharmacopoeia of the People's Republic of China. According to China pharmacopeia, 83 herbs were recorded as toxic herbs.

Data mining process and methods

The frequency and the prescription patterns were analyzed using Microsoft SQL Server 2005 (The Microsoft Association Rules algorithm with the well-known Apriori algorithm). Data mining methods (frequent itemsets) were used to analyze the regular patterns and compatibility laws of the constituent herbs in the selected prescriptions. More than 96,000 prescriptions from Chinese Formulae Database were selected.

Finding frequent itemsets and association rules mining have been studied popularly in data mining research. The apriori algorithm was proposed to discover association rules by generating candidate itemsets with a bottom-up method and repeatedly verifying their supports by scanning a database. The algorithm stops mining when no further candidate itemsets can be generated. The framework has become a common model for mining association rules.

The frequencies of occurrence and use were computed. In addition the associations between different Chinese herbs from the formulae were also examined using the association rules mining.

The support (%) of a herb set X was defined as the proportion of all prescriptions in the data set that contained the herb set X. Support is a measure of how frequently the rule occurs in the database. In this report, support refers to how frequently the herb occurs or used in the database.

The Chinese name of each selected herb was input into Chinese Formulae Database. The frequency of usage was output and listed as xls. style. The detailed process of data mining was showed in Fig. 1.

Results and discussion

Analysis and validation of dual roles of licorice in Chinese Formulae based on data mining analysis in Chinese Formulae Database--Detoxification role of licorice in Chinese Formulae

Licorice is the most commonly used herb in Chinese Formulae Database

As shown in Table 1, Glycyrrhiza uralensis (licorice, gancao) is the most frequently used herbs in Chinese Formulae by data mining analysis in Chinese Formulae Database, which might support the importance of licorice as well as its 'National Venerable Master' and 'nie out of ten herbal formulas contain licorice' description in Chinese Formulae theory. The other commonly used herbs are Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), etc., which are also the famous Chinese herbs.

Radix aconiti lateralis praeparata (Fu zi) is the most commonly used toxic herb in Chinese Formulae Database

According to China pharmacopeia, 83 herbs were recorded as toxic herbs. The names of toxic herbs recorded in Pharmacopoeia of the People's Republic of China was inputed in Chinese Formulae Database and was output with the frequency of these herbs used in the formulae recorded in this database. As shown in Table 2, the most frequently used toxic herbs was Radix aconiti lateralis praeparata (Fu zi), followed by Rhizoma pinelliae (Ban xia), Cinnabaris (Zhu sha), etc.

Rhizoma pinelliae (Ban xia), Radix aconiti lateralis praeparata (Fu zi), Cinnabaris (Zhu sha) are top 3 most frequently used herbs that combined with licorice

The frequency of licorice and 83 herbs used in combination were searched in Chinese Formulae Database. The names of each toxic herb recorded in Pharmacopoeia of the People's Republic of China and licorice was inputed in Chinese Formulae Database, respectively. The result was output as the frequency of these herbs used in combination with licorice in the formulae recorded in this database. As shown in Table 3, Rhizoma pinelliae (Ban xia). Radix aconiti lateralis praeparata (Fu zi), Cinnabaris (Zhu sha) were most frequently used in combination with licorice among all of the recorded toxic herbs, which showed that licorice might reduce the toxic of commonly used toxic herbs. The network of frequency of these herbs used in combination with licorice in the formulae was showed in Fig. 2.

In TCM theory, all medicinal are described as nature of cold, cool, neutral, warm, or hot. "Cool" and "cold" herbs can be used to treat heat diseases such as high fever, strong sweating. "Warm" and "hot" herbs can be used to treat cold diseases like cold limbs, aversion to cold, watery diarrhea. Moreover, "warm"/"hot" herbs are more likely to lead to serious adverse reactions in respiratory and cardiovascular system comparing with "cold" herbs (Wang et al. 2013). For example, Radix aconiti lateralis praeparata was classified to be "hot" herbs which are likely to cause systemic numbness, a reduction in reflexes, difficulty in swallowing, etc. The cold nature of licorice may help to harmonize the adverse reactions of "hot" herbs.

The other question is if licorice is the number 1 herb that used to reduce or eliminate the toxicity of the commonly used toxic herbs? Is there any other herbs that could substitute licorice for its detoxification role?

Detoxification role of licorice in Chinese Formulae. Licorice as a harmonizing and modifying herbs in prescription and eliminating various toxicities--its toxicity attenuating role

Validation for the detoxification role of licorice in ancient Chinese clinical usage--frequency analysis of licorice prescribed with toxic herbs in formulae by Data mining analysis in Chinese Formulae Database.

The top 10 herbs which were most commonly used in combination with licorice were listed in Table 3. So as to these 10 herbs, what is the ratio of these herbs used in combination with licorice comparing to their total usage frequency?

The frequency ratio was calculated as "frequency of a herb that used in combination with Iicorice"/"total number of prescriptions containing this herb" * 100%. As the data showed in Table 4, more than 50% usage of Pericarpium papaveris (Ying su ke), Raix dichroae (Chang shan), Rhizoma pinelliae (Ban xia) must be used in combination with licorice.

In 83 toxic herbs, 11 herbs were used in combination with licorice at more than 20% ratio, which means that if these 29 herbs were used for 100 times in formulae combined with other herbs, they will be used for more than 20 times in combination with licorice. This result further supplied the description of licorice as the most important detoxification herb. According to the Chinese Prescription Database analysis of Radix Aconiti Lateralis Praeparata, out of a total of 8111 prescriptions, 29.8% (2420) are combined with liquorice. Liquorice significantly reduces the toxicity of aconite when the two herbs are decocted together.

Rhizoma pinelliae (Ban xia), Radix aconiti lateralis praeparata (Fu zi) and Raix dichroae (Chang shan) depend on licorice but not other herbs

The other question is if licorice is the number 1 herb that mostly used to reduce or eliminate the commonly used toxic herbs? Are there any other herbs that could substitute licorice for its detoxification role?

Data (Table 5) showed that among the most frequently used toxic herbs described above; the combination frequency of licorice with 10 herbs was among the top 10. For example, Rhizoma pinelliae (Ban xia), Radix aconiti lateralis praeparata (Fu zi) and Raix dichroae (Chang shan) were highly and frequently used in combination with licorice but not other herbs.

Licorice as a harmonizing and modifying herbs in a prescription and eliminating various toxicities--strengthen efficacy

Licorice could harmonize the most frequently used herbs

Radix et rhizoma ginseng (Ren shen), Poria (Fu ling) and Radix Angelicae Sinensis (Dang gui) were the most frequently used herbs in combination with licorice. The other top 20 herbs were also shown in Table 6. In these 10 herbs, Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), Poria (Fu ling) and Radix atractylodis macrocephalae (Bai zhu) were also among the top 20 most frequently used herbs. Based on these data, we concluded that licorice could harmonize the most frequently used herbs such as Radix Angelicae Sinensis (Dang gui), Radix et rhizoma ginseng (Ren shen), etc.

Incompatible of licorice with argassum (Hai Zao), Herba Cirsii Japonici (Da Ji), Euphorbia kansui(Gan Sui) and Flosgenkwa (Yuan Hua) (inducing and enhancing toxicity)

We calculated the frequency of licorice combined with argassum (Hai Zao), Herba Cirsii Japonici (Daji), Euphorbia kansui (Gan Sui) and Flosgenkwa (Yuan Hua). The result showed that licorice is seldomly used in combination with these four herbs.

For example, Sargassum (Hai zao), it has been clearly stated "Not to be used with licorice" in traditional and modern TCM documents such as "Compendium of Materia Medica" (Ben Cao Gang Mu) and the Chinese pharmacopeia. In most cases, the combination of these two medicines is forbidden due to possible adverse effects. Similar warnings of adverse effects with licorice are not found for another brown seaweed, KunBu, traditionally used in TCM (also named as Laminaria Thallusor Ecklonia Thallus in Chinese Pharmacopeia) (Liu et al. 2012b). Chemical component licorice-herbs interaction and pharmacological activity, toxicology interaction between licorice and other herbs have been studied recently (Chen et al. 2012a, 2012b; Ding et al. 2012; Heng et al. 2013; Ji et al. 2012; Yu et al. 2013). This traditional caution regarding the use of licorice and Sargassum together may be explained by opposing effects on immune function and needs to be investigated in more detail.

Most of Chinese medicines are used in combination with each other. The additive, synergistic or antagonistic effect might exist during their usage in combination. Successful use of herbal drug combinations in traditional medicine makes it necessary and important to study the interaction profile such as the synergy research, which has been supposed in recent years (Wagner 2011; Wagner and Ulrich-Merzenich 2009; Ulrich-Merzenich et al. 2009). Synergistic/antagonistic effects can be produced if the constituents of an extract affect different targets or interact with one another in order to improve/decrease the solubility and thereby enhance/decrease the bioavailability of one or several substances of an extract.

Recently there are many reports about the synergistic interactions between nature components or with chemical synthesized compounds (Novy et al. 2013; Eid et al. 2012). And the combination therapy has also been applied in the clinic (Rather et al. 2013; Prabhakar et al. 2014). Among the many methods proposed to study synergistic/antagonistic effects, the "isobole method" of Berenbaum seems to be one of the most practicable in terms of experimental design, and also the most effective in demonstrating synergy (Berenbaum 1989).

As to licorice, it has been reported that licorice extract could potentiate other substances and acts as detoxifier, which could explain why licorice is the top 1 herb prescribed in formulae recorded in Chinese Formulae books. In the contrary, it was recorded that when licorice was used in combination with some other herbs such as argassum (Hai Zao), Herba Cirsii Japonici (Da Ji), some side effects or toxicity might happen. To explain this phenomenon, the synergistic or antagonistic research should be used. For example, licorice might enhance the solubility of toxic components of argassum (Hai Zao) and Herba Cirsii Japonici (Da Ji) and therefore lead to toxicity when used in combination.

For complex formula, synergistic or antagonistic effect can be hardly observed and proved because the formula is commonly composed of several herbs. And even for one herb, it consists of complex mixtures of major compounds, minor concomitant agents and fibers, which can all be involved in the synergistic or antagonistic effects (Wagner 2011; Wagner and Ulrich-Merzenich 2009). Therefore, the research strategy in formulae to prove synergistic or antagonistic effects must be different from that of classical medicine and new methods such as the "omic"-technologies should be used (Ulrich-Merzenich et al. 2009).

Conclusions

Application description of Chinese Formulae in ancient China and modern medicine

According to data mining analysis in Chinese Formulae Database, Licorice is calculated to be the top 1 herb prescribed in formulae that recorded in Chinese Formulae books (Table 1). Licorice is also the top 3 mostly studied herbs by searching in internet academic database (2000-2012). Based on this aspect, licorice could be considered as the most important herb and the focus of research in Chinese medicine. Further synergistic or antagonistic studies are needed to evaluate and validate dual roles of licorice based on modern biology methods and models.

Abbreviations for graphical abstract and Fig. 2.

Abbreviation      Botanical name

SAA               Semen armeniacae
                  amarum

PP                Pericarpium
                  papaveris

RD                Raix dichroae

RhP               Rhizoma pinelliae

RRST              Radix et rhizoma sophorae
                  tonkinensis

RAR               Rhizoma anemones
                  raddeamae

RhPa              Rhizoma paridis

FT                Fructus tribuli

FX                Fructus xanthii

SG                Semen ginkgo

SH                Semen hyoscyami

RALP              Radix aconiti lateralis
                  praeparata

RhC               Rhizoma
                  curculiginis

Scor              Scorpio

FE                Fructus evodiae

FAA               Folium artemisiae
                  argyi

RA                Radix aconiti

RhT               Rhizoma Typhonii

RrT               Rructus toosendan

RAK               Radix aconiti kusnezoffii

Cin               Cinnabaris

SM                Semen momordicae

Scol              Scolopendra

EK                Euphorbia kansui

RrC               Fructus cnidii

RhA               Rhizoma Arisaematis

Hir               Hirudo

RT                Resina toxicodendri

Rae               Realgar

RC                Rructus carpesii

SP                Semen pharbitidis

FG                Flos genkwa

RGA               Fructus gleditsiae
                  abnormalis

SR                Semen ricini

RaP               Radix phytolaccae

VB                Venenum bufonis

SCP               Semen crotonis pulveratum


FC                Fructus crotonis

Myl               Mylabris

Cal               Calomelas


ARTICLE INFO

Article history:

Received 18 April 2014

Received in revised form 27 May 2014

Accepted 2 July 2014

http://dx.doi.org/10.1016/j.phymed.2014.07.006

Acknowledgements

This work was also financially supported by National Basic Research Program of China (973 Program) (2011CB505300, 2011CB505301, 2011CB505303), "Six Talent Peaks Program" of Jiangsu Province of China (2013 YY-009), Jiangsu 333 Project for the Cultivation of High-level Innovative Talents, Key Research Project in Basic Science of Jiangsu College and University (NO. 13KJA360002), and A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (ysxk-2010).

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Table 1
The top 10 most frequently used herbs in Chinese
Formulae by data mining analysis.

Chinese      English name       Botanical name        Frequency
name         of herb

Gan cao      Licorice           Clycyrrhiza           26,185
                                  uralensis
Dang gui     Chinese Angelica   Radix Angelicae       16,285
                                  Sinensis
Ren shen     Panax Ginseng      Radix et rhizoma      14,154
                                  ginseng
Fu ling      Indian Bread       Poria                 13,624
Bai zhu      Largehead          Radix atractylodis    10,361
               Atractylodes       macrocephalae
               Rhizome
Fang feng    Divaricate         Radix                 8661
               Saposhnikovia      saposhnikoviae
               Root
Mu xiang     Aucklandia Lappa   Radix aucklandiae     8212
Fu zi        Monkshood          Radix aconiti         8111
                                  lateralis
                                  praeparata
Huang qin    Baical             Radix Scutellariae    7903
               Skullcap Root
Huang lian   Golden Thread      Rhizoma coptidis      7504

Chinese Formulae Database contains 96,592 formulae records.
Each record represents a single prescription and provides
the cited information. The data in this database is derived
from 1500 Chinese Formulae books (from 200 BC HAN to 1980)
such as Zhang Zhongjing's "Treatise on Cold Damage and
Miscellaneous Diseases" and Li Shizhen's "The Compendium of
Materia Medica", the most comprehensive documentation of the
use of medicinal herbs, minerals and animal parts.

Table 2
The top 10 most frequently used toxic herbs
in Chinese Formulae by data mining analysis.

Chinese name   Botanical name             Frequency

Fu zi          Radix aconiti lateralis    8111
                 praeparata
Ban xia        Rhizoma pinelliae          7123
Zhu sha        Cinnabaris                 3329
Xiong huang    Realgar                    3229
Ba dou         Fructus crotonis           2348
Wu zhuyu       Fructus evodiae            1971
Qing fen       Calomelas                  1584
Bai fuzi       Rhizoma Typhonii           1497
Quan xie       Scorpio                    1431
Tian nanxing   Rhizoma Arisaematis        1341

Table 3
The top 10 most frequently used herbs that combined
with licorice in Chinese Formulae by data mining
analysis (order by frequency).

Chinese name   Botanical name           Frequency

Ban xia        Rhizoma pinelliae        3724
Fuzi           Radix aconiti            2420
                 lateralis praeparata
Zhu sha        Cinnabaris               594
Wu zhuyu       Fructus evodiae          504
Jill           Fructus tribuli          453
Xiong huang    Realgar                  404
Quan xie       Scorpio                  404
Chuan wu       Radix aconiti            395
Bai fuzi       Rhizoma Typhonii         309
Cao wu         Radix aconiti            223
                 kusnezoffii

Table 4
The top 10 most frequently used toxic herbs that combined
with licorice in Chinese Formulae by data mining analysis
(order by frequency ratio).

Chinese name   Botanical name          Frequency
                                       ratio

Ying suke      Pericarpium papaveris   58%
Chang shan     Raix dichroae           57%
Ban xia        Rhizoma pinelliae       52%
Shan dougen    Radix et rhizoma        50%
                 sophorae
                 tonkinensis
Ji li          Fructus tribuli         35%
Fu zi          Radix aconiti           30%
                 lateralis
                 praeparata
Quan xie       Scorpio                 28%
Wu zhuyu       Fructus evodiae         26%
Ai ye          Folium artemisiae       24%
                 argyi
Chuan wu       Radix aconiti           23%

The frequency ratio was calculated as "frequency of a
herb that used in combination with licorice"/"total number
of prescriptions contain this herb" * 100%.

Table 5
The top 10 most frequently used toxic herbs that combined
with licorice and order of licorice in Chinese Formulae
by data mining analysis.

Chinese name   Botanical name           Order of
                                        licorice

Ban xia        Rhizoma pinelliae        1
Fu zi          Radix aconiti            1
                 lateralis
                 praeparata
Chang shan     Radix dichroae           1
Yingsuke       Pericarpium papaveris    1
Shan dougen    Radix et rhizoma         1
                 sophorae tonkinensis
Ji li          Frucms tribuli           2
Ai ye          Folium artemisiae argyi  4
Zhu sha        Cinnabaris               4
Wu zhuyu       Frucms evodiae           4
Xiong huang    Realgar                  5

Table 6
The top 10 most frequently used herbs that combined with
licorice in Chinese Formulae by data mining analysis.

Chinese name   Botanical name         Frequency

Ren shen       Radix et rhizoma       8107
                 ginseng
Fu ling        Poria                  7270
Dang gui       Radix Angelicae        7193
                 Sinensis
Bai zhu        Radix atractylodis     5740
                 macrocephalae
Huang qin      Radix Scutellariae     4762
Fang feng      Radix saposhnikoviae   4545
Chen pi        Pericarpium citri      4022
                 reticulatea
Chuan xiong    Rhizoma chuanxiong     3835
Ban xia        Rhizoma pinelliae      3724
Jie geng       Radix platycodonis     3314
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Author:Guo, Jianming; Shang, Erxin; Zhao, Jinlong; Fan, Xinsheng; Duan, Jinao; Qian, Dawei; Tao, Weiwei; Ta
Publication:Phytomedicine: International Journal of Phytotherapy & Phytopharmacology
Article Type:Report
Geographic Code:9CHIN
Date:Sep 25, 2014
Words:5215
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