Policies and Problems of Modernizing Ethnomedicine in China: A Focus on the Yi and Dai Traditional Medicines of Yunnan Province

Yunnan is a multiethnic province in southwest China, rich in Materia medica resources, and is popularly known as the kingdom of plants. Biomedicine and public health industry have been the industrial pillars of Yunnan since 2016, which is the important pharmaceutical industrial base for Dai and Yi medicine in China. This review of the Yunnan ethnic medicine industry describes some of the problems to be solved in the development of sustainable ethnomedicine in China. We investigated Chinese patent medicines (CPMs) declared as ethnomedicine on the drug instructions and identified 28 Dai patent medicines (DPMs) and 73 Yi patent medicines (YPMs) that were approved for clinical use in China. In further research, the clinical indications of these CPMs were determined, and the quality standard of medicinal materials and their usage frequencies in DPMs and YPMs were investigated. We also collected and analyzed the data on use of botanical and animal sources of medicines, the rare and endangered medicinal materials, and toxic medicines in DPMs and YPMs. The application of zootherapy in Yi traditional medicine was introduced from its abundant ancient documents and records; based on the “YaGei” theory in Dai traditional medicine, toxic medicines can be relatively safe in DPMs. However, for promoting the Yunnan traditional medicine industry, it is necessary to strengthen medical research to expand evidence-based clinical practice and balance ethnomedicine production and sustainable utilization of Materia medica resources, especially the animal sources of medicines, toxic medicines, and the protected wild resources reported in this survey. Only in this way can industrialization of ethnomedicine promote the improvement of human health.


Introduction
Evidence of the first human use of plants as medicines was observed in the fossil record of the Middle Paleolithic period, which began approximately 60,000 years ago [1]. Traditional medical knowledge and practices developed in different civilizations by the trial-and-error use of local botanicals and other biomaterial resources that accumulated slowly over long periods of time [2]. e World Health Organization (WHO) estimates that herbal medicines currently serve the health needs of approximately 80% of the world's population, especially millions of people living in the vast rural areas of developing countries [3]. e Chinese have one of the oldest and distinct medical systems in the world. Traditional Chinese Medicine (TCM) has a written history of nearly 3000 years and is widely practiced in China [4]. China is a multiracial country with 56 nationalities, 55 of which are officially recognized as ethnic minorities in 18 provinces of China. Each ethnic minority, e.g., the Tibetans, Mongols, Uygurs, Dai, Yi, and Miao, has its own traditional medicine, and each differs slightly in theory and practice from TCM. Ethnomedicine thus refers to the use of traditional medicine guided by the medical theory and practical experience of each ethnic minority [5]. . e fourth national survey of Chinese Materia medica resources is underway with the objective of determining the status of the available resources and investigating the modern value of herbal medicine including ethnic and folk medicines [6]. However, the national application of ethnic medicine in China is a complex issue that involves public policy, ethnic culture, livelihood status, regional economies, the protection of wild resources, etc.
Yunnan is a multiethnic province in southwest China. In addition to the Han nationality, there are 25 ethnic minorities with a population of more than 6,000, including the Yi, Hani, Bai, Dai, Zhuang, Miao, Hui, and Tibetan. e population of ethnic minorities is estimated at over 16 million, accounting for 33.4% of the provincial total population. e Dai and Yi traditional medicine are the representatives of ethnomedicine practiced in Yunnan. Tibetan medicine as practiced in Shangri-La will be described in a subsequent review. Yunnan Province is an important pharmaceutical industry center for Dai medicine and Yi medicine. For example, Yunnan Baiyao, a highly effective patent medicine has originated from the ancient Yi prescription [5]. Biomedicine and public health industry have been the major industries in Yunnan since 2016, and more than 2000 ethnic medicinal resources and more than 10,000 folk prescriptions are native to Yunnan [7].
is review focuses on the Yi and Dai traditional medicine in Yunnan and the potential problems to be encountered in the development of policies favorable to ethnomedicine development.

Historical Changes of Chinese Ethnomedicine Policies
Since 1949, the Chinese government has successively introduced many policies to support and protect the development of ethnomedicine (    [9]. DDTN is also found to prevent cerebral injury in rats with middle cerebral artery-induced ischemic stroke by decreasing the intracellular Ca 2+ concentration and inhibiting the release of excitatory amino acids [10].

Application of Quality Standards for Yi Medicine and Dai Medicine
In China, the quality standards of ethnic medicines and their patent medicines are based on the national standards included in the Chinese Pharmacopoeia, which has covered ethnomedicines since 1977. Previous research on EPMs in the Chinese Pharmacopoeia (2015 edition) found that some traditional medicines did not establish national quality standards, and that 71 traditional medicines, which include 39 EPMs, are not listed in the Chinese Pharmacopoeia [11]. is practice (called "upside-down standards,") that involves quality standards for Chinese patent medicines (CPMs) but no standard for the composition of CPMs affects the safety of CPMs and the healthy development of the Chinese pharmaceutical industry.    Evidence-Based Complementary and Alternative Medicine e provincial standards relating to the Tibetan, the Xinjiang Uygur, the Inner Mongolia, the Guangxi Zhuang Autonomous Region, Qinghai, Sichuan, and Yunnan and Guizhou provinces also apply to the regulation of the quality of ethnic medicines in China [12]. e academy group and enterprise standards are also applicable to the quality of ethnomedicine.  Table 2.

Application of Medicinal Resources in Yi and
Dai Medicine   [13]. Animals are therapeutic arsenals with a significant role in healing. Zootherapy are derived from products of metabolism (e.g., corporal secretions and excrements) or from nonanimal materials such as nests or cocoons [14]. e reasonableness of zootherapy cannot be denied, and evidence supporting their use should be strengthened by modern scientific research. e animal sources of medicines in DPMs and YPMs are listed in Table 3. e use of some animal products in DPMs and YPMs is controversial, e.g., Cordyceps sinensis, Moschus deer musk, and bear bile, because these medicinal materials originate from protected wild animals or by harvesting activities that harm the ecological environment. Nevertheless, the production and   Fortunately, substitutes are available because of the cultivation of Cordyceps and industrial production of artificial musk [15,16]. Bile can be obtained from living, farmed bears but is ethically controversial [17]. Artificial bear bile has been reported to be effective on anticonvulsion, sedative, and choleretic [18].

Medicinal Parts of Botanical Medicines.
Yunnan is rich in Chinese Materia medica resources and is known as the kingdom of plants. e plant parts used in herbal medicines include seeds, berries, roots, leaves, fruits, barks, and flowers and the whole plant itself. From ancient times to the present, people have used crude botanical materials as medicines to maintain vitality and cure disease [19]. e medicinal parts of botanical medicines in DPMs and YPMs are shown in Figure 5. e plant parts included in DPMs and YPMs are similar, with root and rhizomes, the whole plant, and fruit and seeds being the most frequent. e various parts of the medicinal plants contain active components that are responsible for their effectiveness [20] and physical properties that determine their names [21]. For example, Huangqin (Scutellaria baicalensis Georgi) is called "Rijishi" in the Yi language, in which "Ri" means herbaceous plant; "Ji" means root, the medicinal part of the plant; "Shi" indicates that the color is yellow [22]. e continuing usage of herbal medicines prepared from wild roots and rhizomes, fruits and seeds, and whole plants is not sustainable. e best strategy for balancing industrialization and resource protection is replacing wild with cultivated resources [23].

Rare and Endangered Medicinal Materials
e rapidly increasing demand for CPMs is likely to challenge the sustainability of herbal resources in China. At present, 80% of the most frequently used species cannot meet medical demand, and 1,800-2,100 medicinal species are facing extinction [24]. In the China Plant Red Data Book published in 1992, 388 plant species were listed as threatened, with 121 species as endangered and needing first-grade national protection, 110 species as rare needing secondgrade national protection, and 157 species as vulnerable needing third-grade national protection. Of those plant species, 77 are herbal medicines that account for 19.86% of the threatened species [25]. e national key protection name list of wild animals in China includes 257 animal sources. e shortage of medicinal plants available to pharmaceutical companies can be partially reduced by the cultivation of at least 200 herbs, while some special herbs   Table 4. ose plants are protected by the Chinese government and some international nongovernment organizations such as the International Union for Conservation of Nature. Cistanche deserticola Y. C. Ma (Rouchongrong), Panax ginseng C. A. Mey (Renshen), Glycyrrhiza aponic Bat (Gancao), or other rare medicinal materials listed in the catalogs is protected and utilized sustainably in China. However, the number of endangered ethnic-specific medicines is far larger than that recorded in the catalogs; for example, more than 3000 tons of Rodgersia sambucifolia Hemsl. (Yantuo) are collected annually to produce YPMs. e availability of wild Rodgersia plants is sharply reduced, and resources are severely damaged in Luquan, Yongsheng, Yulong, Heqing, and Ninglang counties of Yunnan Province [26], while its cultivation research just began in recent years. Figure 6 shows the planting situation of Rodgersia sambucifolia Hemsl. in the Meizi test ground, which is subordinate to the Institute of Alpine Economics and Botany, Yunnan Academy of Agricultural Sciences. Consequently, 30 traditional medicines have been listed in the Rare Traditional Chinese Herbs of Yunnan Province in Urgent Needs (RTCHYN), and those used in DPMs and YPMs are shown in Table 5 [27].
Medicines with pharmacological activities that are present in traditional ethnomedicine are likely to be clinically useful, but they may also be toxic, especially if used incorrectly or in the wrong amounts. Unlike that for modern drugs, the efficacy and toxicity assessments of these ethnomedicines are based on traditional knowledge and clinical experience rather than on laboratory evaluation [28]. Toxicity associated with the use of Chinese ethnomedicine may occur because of the environment, religious beliefs, or medical practices. e Chinese Pharmacopoeia includes 83 traditional medicines that are considered toxic [29]; some medicines listed in provincial standards of herbal medicines are also considered toxic [30].
Ten toxic medicines are used in 11 DPMs; six of those are included in the Chinese Pharmacopoeia (2015 edition) and four toxic medicines in the SYNP. One toxic medicine is used in Dai traditional medicine, and two toxic medicines are used in Yi traditional medicine. e 40 YPMs include 24 toxic herbs; 12 toxic medicines are in the Chinese Pharmacopoeia (2015 Edition) and 12 are in the SYNP. Four medicines are known as Yi medicines. Although some toxic ethnomedicines are used in DPMs and YPMs, the proprietary medicines are considered safe and approved for use in China because pharmaceutical processing, combining, and decocting contribute to reducing toxicity and enhancing efficacy. In the traditional Dai medicine (TDM), "YaGei" herbs are used to reduce toxicity. e "YaGei" detoxification theory is a unique supplement of TDM [31], and "YaGei" medicines are used as antidotes to relieve adverse reactions caused by food poisoning, drug poisoning, and other substances [32]. Dai people consume antidotes regularly to eliminate the microtoxins from the body, reduce the chance of illness, and prolong life.
Due to the lack of more pharmaceutical information disclosed, as well as the lack of basic research, the safety information of these DPMs and YPMs including toxic medicines is insufficient. e modern toxicological evidence of these toxic medicines is collected and summarized in Tables 6 and 7, focusing on Dai and Yi toxic medicines. e root of Tripterygium hypoglaucum (Levl.) Hutch (Huobahuagen) soaked in wine as an oral medicine is an ancient Yi medicine described in the Ailao Materia Medica in the treatment of arthritis, joint swelling, pain, bruises, and sprains [59]. Boenning hauseniase silicarpa Levl. (Shijiaocao) is described in the Materia Medica in South Yunnan (Dian Nan Ben Cao, AD.1396 -1476) written by Lan Mao as a bitter, pungent, and warm medicine used to treat chest pain, heartache, stomachache, and abdominal distension. Shijiaocao is also described in the Ailao Materia Medica as a treatment for sore throat, gastric pain, and dysentery. It is described as a cure of acute gastroenteritis in combination with the parasite of Zanthoxylum bungeanum in the Wa Die Yi Medical Book, which was written at the end of the Qing Dynasty [60]. Ancient documents describe the usage of the toxic herbs included in the medical practice of Yi, Dai, or other ethnic minorities in Yunnan. Modern toxicological study can ensure their safe and effective use, and further study is warranted to determine how the toxicity reduces while the prescription remains effective.

Concluding Remarks
Ethnomedicine is an important part of TCM that has a unique medical theoretical system and refers to a wide range of healthcare systems/structures, practices, beliefs, and therapeutic techniques that arise from indigenous cultural development. ousands of years of ethnic amalgamation has produced diversity, integration, and differences among the traditional medicine of different Chinese ethnics. Approximately 8, 000 medicinal species are used by 40 ethnic minorities in China, which account for over 70% of the Chinese Materia medica resources. Data from the National Medical Products Administration of China show that there are more than 600 types of EPMs [12]. e Chinese Pharmacopoeia (1977 edition) began to cover DPMs, and some Miao patent medicines and YPMs were collected from the 2015 edition of Chinese Pharmacopoeia. Overall, a total of 39 CPMs were identified as EPMs, 26 EPMs as prescription drugs, and 13 EPMs as OTC drugs [11]. Prescriptions that are not approved by the government were not included in the review evaluated, but are still in use in clinics in regions of China inhabited by ethnic groups.
is review focuses on Dai and Yi traditional medicines in Yunnan Province because of their long histories and descriptions in the ancient medical literature. e earliest book of Yi traditional medicine that can be verified is the Yuanyang Yi Medicine Book, which was written in 957 AD and found in Yuanyang County of Yunnan Province in 1985 [14]. e earliest books of Dai traditional medicine that can be verified are Ge Ya San Ha Ya, which was written in 964-884 BC, and Dang Ha Ya Long, which was written in 1323 AD [61]. ere are 1, 666 Dai medicines [62], nearly 1, 400 Yi Evidence-Based Complementary and Alternative Medicine medicines [13], and 400 medicines are listed in the Yi Materia Medica [63].
ere are 478 Yi medical formulas described in Chinese Yi Medicine Prescriptions Science [64], and 200 Dai medical formulas are in Study on Dai classical prescriptions of China [65]. e numbers of folk formulas from Dai and Yi traditional medicine are not available to record yet. Just as the example of Yunnan Baiyao mentioned before, a series of ethnomedicines in Yunnan were     Yunnan Province expects to produce TCMs including ethnomedicines with a value of 140 billion RMB in 2020 and an average annual growth of more than 15%, accounting for 75% of its production [65].

Evidence-Based Complementary and Alternative Medicine
Five key conclusions can be drawn from this investigation of Dai and Yi medicines.
First, except for the Yunnan Baiyao Group and the Dihon Pharmaceutical Company, most of the pharmaceutical manufacturers of EPMs in Yunnan Province are small enterprises, thereby limiting research and development capacity. A search on the China National Knowledge Infrastructure (CNKI, http://www.cnki.net) found 163 articles that reported investigations of these 28 DPMs reviewed here and 59 articles about Yunnan Baiyao Aerosol, whereas it is only one of the CPMs produced by the Yunnan Baiyao Group. In 2015, 100 million bottles of Yunnan Baiyao Aerosol were produced, with a value of more 1.5 billion RMB. In the same year, the overall sales revenue of the Yunnan Baiyao Group was 20.74 billion RMB [7].
Second, the sale volumes of YPMs and DPMs cannot be grasped, and it is hard to determine the extent to which traditional medicines used in YPMs and DPMs are collected in the wild. is will be a challenge to sustainable utilization for Chinese Materia medica resources.
ird, the use of toxic medicine used in ethnomedicine is of concern. Herbal medicine containing aristolochic acid has been associated with nephropathy in Belgium [66], and the adverse events associated with the use of Xiao Chaihu Tang in Japan [67] have led to warnings of the safety of CPM. Scientific evidence is needed to demonstrate the rationale and necessity of using toxic herbs in EPMs.
Fourth, the identification and usage of traditional medicines vary among ethnic minorities because of differences in experiences of clinical practice. e survey of DPMs and YPMs showed the differences in the number of animal sources of medicines used by the Yi and Dai people. e differences were also found in the ancient medical literature of Yi and Dai minorities.
Fifth, Dai and Yi medical prescriptions were traditionally written in the Dai and Yi languages, but the current clinical indications of DPMs and YPMs are written in Chinese. Difficulties in translation have hampered evaluation of how these ethnic medicines are used. Efforts to obtain accurate translations will be the next important work. e sale volumes of DPMs and YPMs are not available because they belong to trade secrets. Because the descriptions of ethnic medical prescriptions in the ancient literature were written in Yi and Dai languages, they are hard to comprehend. However, the medical practices and culture of ethnic minorities have existed in Yunnan for thousands of years and have resulted in written records of more than 1300 ethnic medicinal materials and nearly 30,000 folk prescriptions. e medical information has been passed on orally or via ancient documents written in various ethnic minority languages such as the San Ma Tou Yi Medical Book and the Lao Wu Dou Yi Medical book written in the late Qing Dynasty of China. e ongoing scientific investigation and sustainable utilization of medicine resources will help to increase the impact of ethnomedicines of Yunnan Province on improvement of human health.

CPM:
Chinese patent medicine ChP: Chinese Pharmacopoeia CK: Creatine kinase CR: Critically endangered Ca 2+ : Calcium ion DPM: Dai patent medicine DDTN: Dan Deng Tong Nao Capsule EM: Ethnic medicine EN: Endangered HT: High toxicity IUCN: List of International Union for Conservation of Nature

Data Availability
e data used to support the findings of this study are available from the first author upon request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
HLQ conceived and designed the whole study and obtained funding. LZY conducted the data collection, interpreted the data, and drafted the manuscript. LCF drew the figures, and TSH evaluated the clinical indications. e herbal resource information was collected by ZXB and CXM. LZY and YHJ analyzed the data. HLQ reviewed and revised the manuscript.