The Exotic Materia Medica of Chinese Medicine: A Survey of Its Resources and Medical Information in 1029 BC–1999 AD


 BackgroundTraditional Chinese medicine (TCM) gives people an image of its medicinal resources all from within China. Nevertheless, the fact is that the Exotic Materia Medica(ECM) has been used in Chinese medicine from Zhou Dynasty (1029 BC-221 AD). However, no extensive studies have focused on it. Now, the high exchange speed of information and material brings TCM opportunities to apply exotic resources in clinics. So, surveying the historical ECM’s resources and medical information is valuable.MethodsWe investigated the origin of 8980 Chinese Materia Medica’s resources included in Chinese Materia Medica and compiled a species list of exotic Chinese medicines (ECM) used in China between 1029 BC–1999 AD and their medical information, introduction time, introduction routes, and place of origin.ResultsConsequently, we found information on 788 ECM and their clinical application. A total of 99% of ECM were found to be botanicals mainly belonging to Solanaceae, Amaranthaceae, Malvaceae, Myrtaceae, and Cruciferae. The exchange speed of these medicines between China and other regions peaked in the Han (206 BC–220 AD), Tang (618–907 AD), and Ming dynasties (1368–1644 AD), and increased sharply from 1912 onwards. The main registered efficacies of the ECM were "clear heat" and diuresis. The most efficient way to convert foreign medicine to TCM is to absorb drugs from foreign regions directly. Last but not least, about One-fifth of commonly used TCM in the clinic is ECM.Conclusion﻿Chinese doctors are more concerned with the efficacy of the drug when using it in clinical settings than whether the drug comes from afar. The record of origin and source was to ensure the supply and quality of the drugs. The use of foreign resources as Chinese medicine is the fact that Chinese medicine objectively exists. The existence of ECM has enriched the resources of TCM. Furthermore, both foreign medicine and local medicine currently protect people's lives and health.


Background
Traditional Chinese medicine (TCM) or Traditional Chinese Materia Medica has provided medical knowledge and resources in China. While exploring and utilizing local medical resources, the Chinese doctor also applies effective foreign medicines to the clinical. The history of using exotic medicines in China can trace back to the Zhou dynasty(1029-221 BC). The Eastern Han philosopher Chong Wang's Lun Heng volume eight "Ruzeng Pian" said: "During the Zhou Dynasty, the world was peaceful, Vietnam sent white pheasants, and Japanese sent tulip grass [1]. " And then, in the Middle Ages, exotic medicines were introduced by the Persians from the Silk Road. Moreover, during the Tang dynasty(618-907 AD), overseas medicines were introduced to China via the Maritime Silk Road due to the development of maritime trade [2]. In the Five Dynasties and Ten Kingdoms period(907-979 AD), the Persian businessman Xun Li's Marine Herbal Medicine systematically recorded the foreign medicines. Exotic medicines have been introduced in medical practice in China during each historical period.
Although the history of using exotic medicines in China can trace back to the Zhou dynasty, modern research on exotic medicines began with the Chinese pharmacist Professor Ling Yikui. He and his student rst de ned exotic Chinese medicine (ECM) in 1980. ECM refers to imported medicines or foreign medicines introduced in China. ECM should: 1) be produced outside the territory, relying solely on importers, such as frankincense, myrrh, benzoin, and storax; 2) be produced outside and inside the territory, imported from abroad, such as Korean ginseng, Dongyang ginseng, American ginseng; 3) rstly produced outside the territory but later introduced in China, such as white cardamom, pepper, cinchona, and coix seed [3].Chinese pharmacists complied with this de nition and inclusion criteria while exploring the ECM [2,[4][5][6][7][8].In this research, we followed the de nition of Yikui Ling, except we emphasized that the original resources came from abroad. ECM covers plants, animals, and minerals or their processed products that have entered China through various methods, and have been used in the Chinese medicine.
Which includes animals and plants originally distributed in China, but the initial resources were from abroad or naturalized in China, such as turmeric, coix seed, American ginseng, patchouli, winter melon seeds. Now, the high exchange speed of information and material brings TCM opportunities to apply exotic resources in the clinic. So, surveying the historical ECM's resources and medical information is valuable.
However, no extensive studies have focused on it. The existing research on ECM have focused on a classic pharmacy book or a certain dynasty [7][8][9][10][11][12][13][14][15][16]. Most of them focusing on a classic pharmacy book or a certain dynasty. Therefore, we compiled a list of ECM from the 8980 traditional Chinese medicines included in the Chinese Materia Medica [17].which covers the drugs that are recorded in all the classic pharmacy books of TCM and still being used today. We then analyzed their place of origin, time of application, time of introduction, characteristics of the resources, drug e cacy, and clinical application.
This study represents the rst attempt at a compilation of the basic general list of ECM with comprehensive analysis of its e cacy, indications, and resources.

Methods
In this research, the de nition of ECM refers to the part of TCM that its initial resources were from abroad, which covers plants, animals, and minerals or their processed products that have entered China through various methods and have been used in Chinese medicine. ECM should: 1) be produced outside the territory, relying solely on importers, such as frankincense, myrrh, benzoin, and storax; 2) be produced outside and inside the territory, the initial resources were from abroad, such as turmeric, coix seed, American ginseng, patchouli, winter melon seeds; 3) rstly produced outside the territory but later introduced in China, such as white cardamom, pepper, cinchona, and coix seed. Under the guidance of the above three standards, we have assessed 8980 Chinese medicines recorded in Chinese Materia Medica [17], Withing the help of Guangyao's Xu research [18].
The scienti c name of plants was determined according to The Plant List database (www.theplantlist.org) and the Chinese Flora database (www.iplant.cn/frps). The scienti c name of the animal resources was determined using www.marinespecies.org/index.php and a-z-animals.com. According to the relevant appendix data of the "Exotic Plants from China" and the Plant Introduction and Conservation Database of the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences (http://sdb.xtbg.ac.cn), we analyzes the introduction pathway, time, and origin. Additional information was collected from journal literature.
A database of ECM based on the aforementioned, including scienti c name, taxonomy information, traditional e cacy, introduction route, introduction time, place of origin, the rst application time (based on history literature), and rst medical literature. The drug application time was mainly based on the rst recording time of traditional Chinese medical literature. We have also referred to Chinese clinical pharmacies and diagnostics to determine the traditional e cacy of ECM. Due to the complex relationship between TCM and biological resources, this study used two standards for statistical analysis of medicinal resources and clinical information: 1) ECM's data of medicinal resource of the original place, family, introduction time, and introduction way were considered as statistic objects; 2) clinical information on e cacy, indication, application time, and the total number of ECM, were set as statistics objects.

Results
A total of 788 ECM among 8980 TCM were retrieved from the Chinese Materia Medica. The ECM's drug names, plant names, sources, effects, indications, medicinal properties, medicinal taste, meridian, medicinal parts, toxicity, introduction route, life type, family, genus, introduction time, rst medical literature of loading, the rst application time, and the place of origin, can be seen in Supplement 1.

Introduction time and routes of ECM
We con rmed the introduction time of the 410 species, and 65 species had not been veri ed. The annual introduction rate of each dynasty is shown in Fig.2  A total of 29 routes for the introduction of ECM in China were found. The main ones (Fig.3) were ornamental (23.05%), fruit and vegetable (22.07%), unintentional introduction (13.41%), medicinal (10.61%), and spice (5.61%). The ECM introduced by these routes accounted for 74.76% of the total. A few species were found to be introduced in China in multiple ways (e.g., nutmeg through medicinal and spice routes).  (Table 1), which shows that the most introduced categories of ECM were "clear heat" and diuresis, suggesting that local ECM may lack resources in these two areas.
The e cacy of the 788 ECM here studied is distributed throughout the major of Chinese clinical medicine.

The indication of ECM
The indications of TCM refer to the main clinical adaptation of the drug, also called the main adaptation range. Ancient Chinese doctors obtain indications of Chinese medicine through clinical practice. The descriptions of ECM indications come from different documents, thus we have analyzed and standardized the treatment of the main treatment of each medicine. The detailed treatment process and results are shown in Supplement 3. A total of 826 indications were reported for ECM. The top 50 were: sore, carbuncle, fall injury, cough, dysentery, diarrhea, edema, rheumatic arthralgia, sore, boil, vomiting blood, eczema, respite, jaundice, vomiting, hot eyes, sore throat, metrorrhagia and metro taxis, scald, blood in stool, boil, di culty in urination, stomach ache, hemoptysis, scabies, gangrene, headache, traumatic bleeding, malaria, irregular menstruation, stomachache, diarrhea, hemorrhoids, leukorrhea, sputum, leucorrhea, toothache, dysmenorrhea, lung fever, bloating, beriberi, blood, food accumulation, constipation, hypertension, scrofula, snakebite, fracture, amenorrhea, and malnutrition. The sum of the frequency of the top 50 accounts for 59% of all attending diseases. The top 10 frequencies were: 162, 151, 142, 129, 110, 80, 76, 63, 59, and 53. Half of the scope of the treatment of foreign Chinese medicine belongs to skin diseases, urinary system diseases, trauma, respiratory diseases, digestive system diseases, and gynecological diseases. This result is consistent with its main effects of clearing heat, diuresis, activating blood to remove blood stasis, hemostasis, relieving cough, relieving cough and asthma, and resolving phlegm.

The dominant families of ECM
To clarify the unique superior families of ECM relative to TCM, we collected the family of 7812 nonanimal and mineral medicine (i.e., algae, lichens, and plant) included in the Chinese Materia Medica (Supplement 4).  (Fig.4).

Directly absorb and convert natural medicines from foreign regions into TCM is Commendable.
The top four introductory routes found were the ornamental route, the fruit and vegetable route, the medicinal route, and the spice route. The number of ECM introduced through the ornamental route was the highest. However, just 11 (pittosporum bark, elderberry, calendula, cassia, trumpet creeper, morning glory, green box, opium, digitalis, poppy, and poppy husk) had high-quality clinical e cacy and pharmacological effects. Although the number of ECM introduced through the fruit and vegetable route is relatively high, they all appear as fruits and vegetables in supermarkets and vegetable markets, rather than medicines in hospitals and pharmacies. The number of ECM introduced through medicinal routes ranks third. More than half of ECM introduced through medicinal routes is commonly used in clinics of Chinese medicine. They are used in hospitals and pharmacies as medicines. The 16 (asafoetida, benzoin, citrus sinensis, aloes, cloves, dried ginger, pepper, horseradish, myrrh, ginger, nutmeg, frankincense, ginger, sesame seeds, cumin, and cumin)items introduced through the spice route in Chinese clinical medicine have the effect of "warming the spleen" and "regulating the stomach, " mainly treating digestive system diseases. This feature is consistent with the current application of spices. To sum up, directly absorb and convert natural medicines from foreign regions into TCM is Commendable (Fig.5).

Trends in the exchange of medical information between China and other regions
Because the time of different dynasties existed and the number of ECM that were introduced during that dynasty were different, we have use 1000 times OF the annual average number of ECM in each dynasty to analyze the tendency (Fig.6). The introduction rate of ECM with different e cacies generally peaked during the Han (206 BC-220 AD), Tang (618-907 AD), and Ming dynasties (1368-1644 AD). In the late Qing dynasty, most types of ECM began to accelerate sharply, in line with the rapid acceleration of the material and information exchange between the East and the West. The exchange speed of medical resources and information between China and other regions increased sharply from 1912 onwards. have not yet been established [19][20][21][22][23]. To obtain the percentage of the CECM accounts for the CTCM, we chose the drugs recorded in The Identi cation of Traditional Chinese Medicine as the CTCM. The Identi cation of Traditional Chinese Medicine is a book of great reference value, which recorded 240 botanical CTCM [24]. With the help of this book, we analyzed the characteristic of different medicinal parts that the CECM accounts for the CTCM (Table 2). Among them, the more prominent is the resin medicinal herbs that account for 100%, which means all of the resin TCM clinically commonly used in clinics belongs to ECM. They are storax, frankincense, myrrh, Asafoetida, benzoin, and dragon's blood. Then it is worth noting that the most frequently used medicinal sites are fruits and seeds. The frequency of clinically commonly used in clinic ECM in fruits and seeds is as high as 13(nutmeg, semen cassiae, boat-fruited scaphium seed, medicine terminalia fruit, fennel fruit, semen strychni, Semen Pharbitidis, henbane, common carpesium fruit, Areca catechu, fructus amomi, fructus amomi rotundus, galanga galangal seed). Last but not least, the percentage of the CECM accounts for the CTCM is 17.1%.

Conclusion
Although the percentage of ECM accounts for TCM in its total resources is 8.8%, the percentage of the CECM accounts for the CTCM is 17.1%.This suggests that Chinese doctors are more concerned with the e cacy of the drug when using it in clinical settings than whether the drug comes from afar. Although in the past, the use of distant drugs meant more money to spend. The famous American Orientalist Laufer said: "The Chinese are a well-thought-out, sensible, and open-minded nation. They have always been willing to accept good things from outsiders [25]" Chinese medicine uses foreign medicine resources for its effectiveness in treatment. Therefore, proactive absorption is the main attitude of Chinese pharmacists when facing effective foreign drugs. The record of origin and source was to ensure the supply and quality of the drugs. Both the accumulation of effective drugs and edible food play an important role in evolution. The use of foreign resources as Chinese medicine is the fact that Chinese medicine objectively exists. The existence of ECM has enriched the resources of TCM. Furthermore, both foreign medicine and local medicine currently protect people's lives and health.  Figure 1 The most dominant family and its introduction route in China.

Figure 2
Page 13/15 Annual average number of introduced species per dynasty.  The common and unique dominant families of exotic Chinese medicines compared with traditional Chinese medicine.

Figure 5
Directly absorb and convert natural medicines from foreign Regions into traditional Chinese medicine is Commendable.