Introduction
Our ancestors worldwide have continuously struggled with diseases to survive and reproduce and thus have gained knowledge and experiences in traditional medicines. For thousands of years, traditional medicines have significantly contributed to human health and life protection. With the increasing demand of human health, traditional medicines exhibit unparalleled advantages in primary health care as well as drug development due to its exact efficacy, good safety and relatively low cost and continue to contribute to human health [
1].
China’s traditional medicines are an important integral and unique part of traditional medicines worldwide. As an old multi-ethnic country, China holds a highly diverse national culture accounting for the varied expression of traditional medicines, including traditional Chinese medicines used by Han Chinese and ethnomedicines used by Tibetan, Mengol, Uygur, Dai, Yi, Miao, and other ethnic minorities. Artemisinin, discovered with the aid of ancient literature that described traditional Chinese medicines, has changed the treatment of numerous vulnerable populations in the past 20 years. Professor Youyou Tu, who was the primary contributor to this discovery, was awarded the 2015 Nobel Prize in Physiology or Medicine. The following examples highlight the development of ethnomedicines of some ethnic minorities. Cheezheng Tibetan Medicine successfully implemented the combination of Tibetan ethnomedicine and modern technology; the Miao ethnomedical industry in Guizhou became a pillar industry in their province; Yunnan Baiyao, a Yi ethnomedicine with “amazing efficacy,” is well known worldwide; and the Erigeron breviscapus series of Miao ethnomedical products and the Gold® series of Yi ethnomedicine established paradigms for the development of new drugs from ethnomedicines. This series of ethnomedicines have been successfully industrialized and modernized to promote the modern vitality of ancient ethnomedicines and thus serve a wide population range.
Ethnomedicines
Concept of ethnomedicines
The term “ethnomedicines” refers to natural medicines that are traditionally used by ethnic groups with different cultural backgrounds [
2]. The term is synonymous to traditional medicines or herbal medicines regarded as products of traditional medicine “based on the theories, beliefs, and experiences indigenous to different cultures; used in the maintenance of health and in the prevention, diagnosis, improvement, or treatment of physical and mental illness” according to the World Health Organization (WHO) [
3]. In China, “ethnomedicines” in its broad sense refers to “China’s traditional medicines,” which had been generated and used over the history of the whole Chinese nationality and remain in use today. China’s traditional medicines usually include traditional Chinese medicines, traditional medicines used by different ethnic groups, and folk medicines widely used for disease prevention or treatment. Among these treatments, the traditional medicines used by ethnic groups are known as “ethnomedicines of Chinese ethnic minorities,” referring to the medicines that are applied under the guidance of the traditional medicine theory or practical experience of each Chinese ethnic minority [
4–
7]. As an important part of China’s traditional medicines, the ethnomedicines of ethnic minorities hold an independent status. Compared with traditional Chinese medicines, ethnomedicines of ethnic minorities show a “sister” relationship in theory and methodology, cultural connotation, and legislation and thus receive the same attention [
6,
8].
Cultural characteristics of ethnomedicines
Given historical conditions and other factors, the level of the development and heritage of the ethnomedicines of different minorities vary. Nevertheless, the producing and developing of ethnomedicines is associated with the national historical and cultural background as well as the level of production and living. The ethnomedicines are permeated with national cultural characteristics, which mainly include traditional characteristics, regional characteristics, and word-of-mouth inheritance [
6]. The traditional characteristics are manifested as a profound cultural background and historical continuity, whereas the permeation of regional characteristics is reflected by the close link of ethnomedical selection and application to weather conditions, natural resources, and living customs in the area inhabited by the particular nationality. Word-of-mouth inheritance is observed in ethnomedicines that had not yet formed a complete theoretical system, in particular, the ethnomedicines used by minorities without an ethnic character. In such classification, ethnomedical practices are mainly passed on by verbal and face-to-face instructions from generation to generation [
6,
8,
9].
Ethnopharmacology and related research
Connotations of ethnopharmacology
The exact definition of ethnopharmacology was proposed internationally in 1981. Bruhn and Holmstedt described ethnopharmacology as “the interdisciplinary scientific exploration of biologically active agents traditionally employed or observed by man” [
10]. In China, the ethnomedicines has been extensively explored since the 1970s; consequently, the ethnopharmacologic study of ethnomedicines was gradually implemented and widely recognized by the academic community [
7,
11,
12]. Ethnopharmacology is a systematic exploration that involves the people, the ethnomedicine, and the relationships between the two components. This field of study aims to analyze the knowledge and practice of each minority with the goal of understanding and applying the traditional medicines of different ethnic groups [
13–
15].
Research content and methods of ethnopharmacology
Ethnopharmacological research mainly covers the following aspects: ethnomedical literature collation, modern drug screening, rational resource protection, quality validation of ethnomedical varieties, and ethnomedical exploration and drug development [
16]. Such research field involves traditional theory and practical experience, medicinal resources, chemical components, pharmacological activity, safety, clinical application, and management. Some scholars believe that a systematic study in ethnopharmacology essentially includes three stages: description, interpretation, and application [
7,
17]. A study in ethnopharmacology mainly involves the methods of medical anthropology, ethnobotany, plant chemistry, pharmacology, and mathematical statistics, and also combines theoretical research, field surveys, and experimental study [
18]. In summary, ethnopharmacology is an inter-era discipline and involves interdisciplinary research tools, resulting in higher requirements for the personnel engaged in ethnopharmacological research. Thus, in practice, only a collaborative research group consisting of professionals experienced in these different fields can complete the systematic study in this discipline [
17].
Particularity of ethnomedicine research
Ethnomedicines originated in the historical practice of ethnic minorities and reflected the understanding of the ethnic peoples regarding life, health, and disease as well as their philosophy to be harmonious with nature. This knowledge deviates far from modern scientific standards, but some of their concepts are rational, feasible, and are often acceptable to most users [
17]. Thus, when introducing modern ideas, methods, and technical means to ethnomedical research, one must balance the relationship between inheritance and innovation. In particular, the characteristics of ethnomedicine should be respected in the scientific analysis for the rational reservation or abandonment of traditional knowledge and experiences in ethnomedicine. Considerable effort must also be directed into natural resource protection and national culture promotion. Furthermore, the minority population must be ensured that the purpose for exploring ethnomedical knowledge and experiences would share their interests, such that ethnomedicine can continue to serve human society [
12].
General information of ethnomedicines worldwide
Major ethnomedicines worldwide
Currently, the world consists of more than 220 countries and regions and more than 2000 ethnic populations of different sizes. During constant turmoil and harmonious coexistence with nature, people of various ethnic groups have accumulated a wealth of medical knowledge and practical experience. As a result, many different traditional medicines (and systems) have arisen and developed in different parts of the world (Table 1) [
19].
In East Asia and parts of Southeast Asia, traditional Chinese medicine involves a complete theoretical system and is extremely popular. In addition, China’s Tibetan, Mongolian, Uygur, Dai, and other ethnic minorities all have their own characteristic medication theory and experience, as well as highly abundant medicinal resources, with increasing domestic and international influence. According to statistics, more than 10 000 types of traditional medicinal plant resources, including those used for traditional Chinese medicine, ethnic medicine, and folk medicine, exist in China. In South Asia, Indian Ayurvedic medicine holds a long history of application, occupies an important position in the national health care system, and encompasses more than 2500 types of traditional medicines. Greco-Arabic medicine remains widely used in West Asia, North Africa, and Southern Europe, with more than 1500 types of traditional medicines. East, West, and South Africa mainly adopt African traditional medicine, which comprises approximately 1000 types of traditional medicines, involving mostly tropical plants. Latin America includes many ethnic groups and popular reputation for traditional medicine, with more than 5000 types of traditional medicines. Europe and Oceania generated fewer traditional medicine approaches. Australian aborigines hold a good foundation for the application of traditional medicines, with approximately 1500 types of traditional medicines [
19,
20].
Current status of traditional medicine application
According to incomplete statistics from the WHO, traditional medicines are currently considered highly reliable and are widely utilized in developing countries; 80% of the world’s population uses local traditional medicines. In the developed world, people are increasingly using traditional medicines because of concerns regarding the potential side effects of synthetic drugs [
21]. Traditional medication involves the use of herbal medicines, animal parts, and minerals. This section focuses on herbal medicines because they are the most widely used among the three sources and the other two types of materials involve other complex factors.
In a survey performed in April 2004 by the United States (US) magazine
Whole Foods, 54% of respondents believed that plant extracts and their preparations are beneficial. Among these subjects, 70% believed that plant extracts are effective against colds; 61%, against depression and anxiety; and 54%, against menstrual syndromes [
22]. Although accurately assessing the global consumption of traditional and complementary medicinal products is difficult to achieve, available data indicate large-scale use. For example, the traditional medicine industrial output value in China reached 730.2 billion yuan in 2014; in South Korea, the annual expenditure on traditional medicine was $4.4 billion in 2004 and increased to $7.4 billion in 2009; in the US, the 2008 out-of-pocket expenses for natural products were $14.8 billion. In addition, in North America, Europe, and Africa, approximately 75% of HIV infected/AIDS patients use traditional medicine to treat various concurrent symptoms [
3].
The trade of botanicals extends throughout the world, mainly in the form of plant extracts, decoction pieces, patent medicines, and health care products. In China, for example, traditional medicine export reached $3.14 billion in 2013, of which plant extracts and decoction pieces accounted for 83.6% of the total export (http://www.cccmhpie.org.cn/Pub/1757/104845.shtml). Currently, the export of China’s traditional medicines involves more than 170 countries and regions, and more than 40 varieties of exported plant extracts and health care products exist, with an output value exceeding that of traditional patented medicines. The largest amount of sales is found in Asia, followed by Europe. The total value of plant extracts is greater than that of patented medicines, especially in North America and Europe. Traditional patent medicines are most popular in Latin America and Africa. Over the past 20 years, the global market for botanicals has continuously grown, and the European market accounts for the largest share of the global market at approximately 35%. In 2005, the global trade volume of botanicals reached 26 billion US dollars and accounted for 30% of the global pharmaceutical market. The markets of botanicals in Europe, the US, Asia, and Japan respectively accounted for 34.5%, 21%, 26%, and 11% of the global botanical market. The annual growth rates for the global markets of botanicals and extracts are up to 10% to 20% and 15% to 20%, respectively, which are greater than the global pharmaceutical market growth rate [
23].
Regulation of traditional medicines
Legal status
When mankind entered the 20th century, early modern medicine that had evolved in the West gradually developed into modern medicine after absorbing and utilizing modern science and technology. This kind of medicine has been widely accepted worldwide as mainstream medicine in various countries and regions. Western modern medicine not only led to changes in global medical structures and patterns but also caused changes in the legal status of traditional medicines. We summarize the four main types of legal statuses of traditional medicines in modern society as follows [
24].
The first type of status is equal rights and coexistence. In this scenario, traditional medicines and modern medicines hold the same legal status, and the government involves specialized agencies that manage traditional medicines. A traditional medicine-based medical treatment system, research system, educational system, and industrial system exist, are acknowledged and supported by the government, and regulated by corresponding laws and rules. Traditional medicines are registered and managed as medications and covered by health insurance (or public health). Representative countries holding the above-mentioned status include China, Vietnam, South Korea, India, North Korea, Sri Lanka, Bangladesh, Pakistan, Nepal, and Bhutan.
In the second type of status, traditional medicine is neither recognized nor banned and does not entail nor is eligible for registration as medication. People working with traditional medicines do not have to possess the credentials of a pharmacist. The law does not prohibit the production and sale of traditional medicines; instead, the law considers this phenomenon as a general commercial activity. In addition, oral traditional medicines are regarded as food or functional food. The representative countries include Malaysia, Indonesia, Mongolia, France, and countries in Oceania.
The third type of status is limited recognition. Certain parts of traditional medicines are recognized without restrictive conditions. For example, Japan recognizes traditional Chinese medicine as drugs but only the preparations that are produced according to the prescriptions in Treatise on Cold Pathogenic and Miscellaneous Diseases written by Zhang Zhongjing. Another example is the European Union (EU) 2004 Traditional Herbal Registration Process Instructions (DIRECTIVE 2004/24/EC). This directive specifies that traditional botanicals can undergo simplified registration and production and distribution as traditional botanical medicines, but these medicines must have over 30 years of application history and at least 15 years of application history in the EU.
The fourth type of status involves the prohibition of traditional medicine. The medical status of traditional medicines is not acknowledged, and traditional medicines cannot be used to treat people. This status is rare and found in Cyprus.
Notably, the legal statuses of traditional medicines in various countries and regions are not static but continue to undergo dynamic changes.
Current status of monitoring and regulation
The WHO, EU, and other international organizations, as well as many countries and regions, especially China and the US, have exerted great efforts in regulating botanicals. Since 1986, herbal medicines have been a dedicated discussion topic in various international conferences on drug regulation authorities. In the traditional and complementary medicine sector, the national regulatory authorities responsible for supervising herbal medicines have held annual meetings since 2006 as part of the global control network for herbal medicine regulation and cooperation. The WHO considers herbs as “traditional and complementary medicine products” and believes that herbs with guaranteed quality, safety, and efficacy contribute to ensuring the target of universal access to health care. The organization has incorporated herbal medicines in various resolutions and strategies related to traditional medicine and has established a relevant drug encyclopedia; guidelines for application, evaluation, registration, and regulation; and technical guidance for production and quality control to promote the regulation and the safe and effective use of herbal medicines. Since the release of the first global strategy for traditional medicine development (WHO Traditional Medicine Strategy 2002–2005) the member countries have clarified or established national and regional policies and laws that promote the safe and effective use of traditional and complementary medicine. The WHO Traditional Medicine Strategy 2014–2023 indicated that the number of affiliate countries implementing herbal medicine regulation has reached 119.
According to the WHO definition, herbal medicines include herbs, herbal materials, herbal preparations and finished herbal products, that contain as active ingredients parts of plants, or other plant materials, or combinations thereof [
25]. Indeed, most herbal medicines remain employed as a complex mixture of compounds for therapy globally, bringing much more challenging issues in the research and assessment of herbal medicinal products [
26]. Since 1991, the WHO has issued a series of technical guidelines, such as
Guidelines for the assessment of herbal medicines and
Research guidelines for evaluating the safety of herbal medicines. In 2004, the European Parliament and Council enacted DIRECTIVE 2004/24/EC. When evaluating the quality, efficacy, and safety of botanicals, this directive fully considers the characteristics of these substances. To date, more than 1000 types of botanicals that have been developed from substances traditionally used in Europe have been approved for marketing on the basis of this directive [
27]. Additionally, in 2004, the Food and Drug Administration (FDA) of the US issued independent
Guidance for Industry for Botanical Products to facilitate botanical research and production. However, to date, the FDA has only approved a total of two new herbal drugs, Veregen and Fulyzaq. The former was developed on the basis of green tea extract and is used for the topical treatment of genital and perianal warts, whereas the latter is the first FDA-approved oral botanical and adopted to treat HIV/AIDS-related diarrhea [
28].
Research and development of traditional medicines
The biological diversity of plants and their traditional applications passed down through generations support not only the development of traditional health care systems but also the discovery of new chemical entities and drugs. In previous years, nature has been regarded as a “treasure trove” of new chemical molecules. According to statistics, approximately one-third of current drugs are derived from plants. Examples include morphine, atropine, artemisinin (its derivatives are often used currently), emetine, berberine, curcumin, and chemotherapy drugs, such as taxol and camptothecin.
Artemisinin was discovered in the 1960s in China through a project code-named “523.” The discovery benefitted from the records of the application of Qinghao (
Artemisia annua L.) as an antimalarial plant in the ancient Chinese medical literature and recipes, especially the description “take one bunch of Qinghao, soak in two litres of water, wring it out to obtain the juice, and ingest it in its entirety” in
The Handbook of Prescriptions for Emergency Treatments written by Ge Hong during the Eastern Jin Dynasty. This work of literature was key in guiding the scientists in successfully extracting the active component, artemisinin. Artemisinin has been employed as a frontline treatment since the late 1990s and has saved countless lives, especially the poorest children in the world [
29]. According to the WHO statistics, about 240 million people in sub-Saharan Africa has benefitted from the medical product and 1.5 million lives have been rescued by artemisinin-based combination therapy (http://www.fmprc.gov.cn/zflt/eng/zxxx/t1309891.htm). Youyou Tu, a Chinese scientist inspired by traditional Chinese medicine, was rewarded the 2015 Nobel Prize in Physiology or Medicine with one half for her major contribution in this artemisinin research (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.pdf).
Europe and North America are active areas for the research and development of herbal medicines. Since the 20th century, European and American countries have achieved great strides in modern botanical medical research and development. The key objectives of the US in the development and utilization of medicinal herbal resources are to discover novel anti-tumor and anti-AIDS drugs. In the US, 6700 crude preparations have been obtained by screening 20 525 types of plants in 4716 genera, and the number of screened plants equals the total number of plants screened by the remaining countries in the world to identify anti-tumor drugs. The new anti-tumor drug taxol and the camptothecin series of derivatives have been approved by the FDA as new anticancer drugs. Popular herbal medicine varieties in European markets include preparations developed using
Ginkgo biloba,
Mentha haplocalyx,
Hypericum perforatum,
Milk thistle,
Saw palmetto,
Echinacea angustifolia, and
Piper methysticum. The total sales of ginkgo preparations in Europe and other world markets have surpassed 2 billion dollars [
30].
Japan also substantially invests in the research and development of traditional medicines based mainly on Kampo preparations. The production of 10 types of Kampo preparations consist of “seven decoctions, two powders, and one pill,” including Buzhong Yiqi decoction, Xiaoqinglong decoction, Liujunzi decoction, and Jiawei Xiaoyao powder, which account for more than 50% of all Kampo preparations. In addition, Japan developed Kyushin pills on the basis of the traditional Chinese medicine Liushen pills. The annual sales of Kyushin pills have reached billions of dollars. In China, since the implementation of the “Drug Administration Law” in 1985, research and development on traditional medicines has been a highly active area and the most important direction in novel drug development. According to statistics, in the 25 years from 1985 to 2010, approximately 3000 new drugs based on traditional medicines were approved for marketing, including nearly 60% of compound drugs, 35% of drugs with changes in the dosage form, and approximately 5% of new drugs consisting of active ingredients and components. In recent years, the secondary development of main traditional medicine varieties has attained significant progress. Through 2011, the number of traditional medicine varieties with sales of a single product over 100 million yuan was 305, and the number of medicines with sales of a single product over 1 billion yuan was 20, including the compound Danshen dropping pill, Yunnan Baiyao aerosol, and the Xuesaitong injection. The main traditional medicine varieties have gradually formed different groups [
31].
With the strengthening of international exchanges and the expansion of scientific research, different systems of traditional medicine continually enhanced the exchange and collaboration of theories, applications, varieties, and other aspects. Some visionary multinational companies have targeted large countries and regions with rich biological resources, such as Brazil, China, India, and Latin America. Many companies have established research and development centers for new plant resources in Peru, Nicaragua, Colombia, and other countries. South Africa and the US have co-invested over 100 million US dollars to establish a research and development organization for new plant resources in South Africa. The US National Institutes of Health and the AIDS Prevention Center are stepping up research on screening and investigating active ingredients of Chinese herbal medicines. Over the past 10 years, the 15 largest multinational pharmaceutical companies have demonstrated an annual increase up to 22.5% in their botanical medicine research expenditure and have established research and development centers in China, preparing the strategic layout required for entering the traditional medicine industry. For example, Novartis established the eighth largest global research and development center in China in 2005, which focuses on Chinese herbal medicines as the major research and development project. Pfizer also formulated a global herbal medicine plan and established a Chinese herbal medicine group in China to evaluate promising traditional medicine prescriptions for development [
30].
General information of ethnomedicines in China
A brief history of ethnomedicines
A brief history of ethnomedicines can be basically divided into five stages, namely initialization, accumulation, theory formation, development, and revitalization. The ancestors of different minorities obtained knowledge of these medicines from nature intentionally or unintentionally, leading to the initiation of ethnomedicines. With the development of economy, society, and culture, the development of the ethnomedicines entered the accumulation stage, and medical knowledge was spread in the form of verbal instructions or songs, or appeared in the early books. Further development of social productivity promoted the refinement of social division as well as the birth of characters and cultural communication, allowing the gradual theorization of knowledge and experience in the ethnomedicines. Cultural exchange deepened in improving in the level of social productivity, science and culture. Ethnomedicines entered the stage of vigorous development, generating a large number of relevant books and establishing an educational system in ethnic medicine, which strongly promoted the inheritance and development of the ethnomedicine theory. After the founding of the People’s Republic of China (P. R. China), ethnomedicines attained their rightful position in history and gradually entered a new period of revitalization. During this stage, a series of policies that support the development of ethnic medicine were issued. Additionally, the survey, exploration, and collation of ethnomedicines were conducted in an orderly manner, an in-depth investigation of medicinal resources was performed, and research and education of ethnomedicines were also gradually standardized, leading to the rise and gradual growth of the ethnomedicine industry [
32–
36].
China’s 55 ethnic minorities developed and accumulated their own traditional medicines throughout the historical period. To date, the theories or experiences of ethnic medicines of more than 30 minorities have been systematically collated and studied. In accordance with their current development, ethnomedicines can be roughly classified into the following three categories. The first category corresponds to mature ethnomedicines, for which a large amount of historical documents, records, and monographs or systematic word of mouth, a wealth of practical experience, and an industry with certain scale, the brand and the developed foundation, and includes the ethnomedicines of six minorities, namely Tibetan, Mongolian, Uygur, Dai, Yi, and Miao. The second category refers to ethnomedicines in development, which involves medical literature or monographs and a rich experience of their administration but not a complete theoretical system, and mainly includes the ethnomedicines of the Zhuang, Qiang, She, Korea, Yao, Dong, Tujia, and Kazak ethnic groups. The third category constitutes of the ethnomedicines with no written historical document or theoretical system, and of which the medication knowledge and experience were solely inherited by verbal and face-to-face instructions, but the medicines show distinctive treatment characteristics. The ethnomedicines included in this category include those of the Shui, Bai, Va, Hui minorities and so on [
9].
Regular pattern of ethnomedicine development
Usually, each ethnomedicine has its unique development path. During the same period, different ethnomedicines might be at different stages of development. Because of the effect of national integration, changes, and other historical phenomena, not all ethnomedicines sequentially experienced the five development stages described above, and some even showed a development path in which some of the stages were skipped. Nevertheless, the different development paths show some common characteristics. For example, the origin and development of ethnomedicines are rooted in the traditional cultures of all ethnic groups; the origin and development of ethnomedicines are based on the repeated exploration process of “Practice, Thinking, Practice Again, and Rethinking.” Cultural exchange is an important impetus for ethnomedical development; and the development of ethnomedicines is consistent with the economic and social development as well as the ecological environment of the ethnic region.
Development status of ethnomedicines
Exploration and rescue of ethnomedicines
According to the principle of “adjust, consolidate, enrich, and improve” proposed for the development of ethnic medicine in the early 1960s in China, much effort had been exerted in the orderly investigation, exploration, collation, and protection of ethnic medicine. The theory of ethnomedicines has been systematically organized, and a number of representative books, including many classic works, such as the Tibetan
Jindru Bencao, Mongolian
Meng Yao Zheng Dian, and Dai
Dang Haya, have been published. Given the review of ancient literature, the study of resources, applied development, and clinical application, the ethnomedicines of some ethnic areas of China were systematically collated and studied. Approximately 50–60 types of records, prescription collections, selections, directories, and illustrations of ethnomedicines have been edited and published, including
Chinese Ethnomedicines Record,
Uygur Ethnomedicines Record,
Yi Ethnomedicines Record,
Miao Ethnomedicines Collection,
Yunnan Ethnomedicines Record, and
Li Ethnomedicines Record. In the 1990s, the State Administration of Traditional Chinese Medicine compiled the
Chinese Materia Medica with five volumes of ethnomedicines, including Tibetan ethnomedicines, Mongolian ethnomedicine, Uygur ethnomedicines, Dai ethnomedicines, and Miao ethnomedicines, all of which were published by the end of 2005 [
37].
Investigation of ethnomedicine resources
The third “National Census of Chinese Medicine Resources,” which was initiated in 1983, verified that more than 8000 medicinal materials are used as ethnomedicines, accounting for approximately 62.5% of the total 12 807 types of medicinal resources in China. However, some medicinal materials may be considered as both a traditional Chinese medicine and an ethnomedicine. Surveys of medicinal resources at different scales have been performed in ethnic regions. According to incomplete statistics, surveys of medicinal resources at varying scales were conducted in 35 ethnic minorities, resulting in the identification of nearly 3000 types of Tibetan ethnomedicines, more than 2200 types of Mongolian ethnomedicines, more than 1100 Uygur ethnomedicines, more than 500 types of Miao ethnomedicines, and more than 700 Zhuang ethnomedicines [
38]. For example, the 25 minorities in the multi-ethnic Yunnan Province use more than 3000 types of medicinal plants, including 1400 types of ethnomedicines that have been recorded. In this province, more than 900 Tibetan ethnomedicines, more than 500 Yi ethnomedicines, nearly 300 Achang ethnomedicines, nearly 200 Lisu ethnomedicines, and more than 170 De’ang ethnomedicines are commonly used [
39–
41].
Education and research on ethnomedicines
With increasing research on ethnomedicines, ethnopharmacology has gradually become widely recognized in the field of scientific research. According to a statistical analysis, during the period of the “Tenth Five-Year Plan,” 25 ethnomedicine projects were included in the science and technology program of the State Administration of Traditional Chinese Medicine. During the period of the “Eleventh Five-Year Plan,” 26 ethnopharmacological projects were accepted as key scientific and technological projects. During the period of the “Twelfth Five-Year Plan,” many ethnomedicine projects, including “The study of the key common technology in the development of the Miao, Dai, and Li ethnomedicines,” “The key characteristic technology research in the production and processing of ethnomedicines,” and “The research and development as well as the technology upgrading for ethnomedicines,” were approved and funded. Beijing, Tibet, Yunnan, and Xinjiang have established research institutions for ethnomedicines. Colleges and universities, such as Tibetan Medical College of Tibet, Inner Mongolia University for the Nationalities, College of Xinjiang Uygur Medicine, and Minzu University of China, have trained a large number of ethnomedicine researchers. Many national-level research institutes and key universities, such as the Chinese Academy of Traditional Chinese Medicine, some institutes of the Chinese Academy of Sciences, and Tsinghua University, as well as some provincial institutes and ethnomedicine enterprises, such as Yunnan Institute of Materia Medica and Cheezheng Tibetan Medicine Co., Ltd., have also invested great effort in literature collation, resource study, and clinical observation, which play an important role in accelerating the development of ethnomedicine research [
33,
42,
43].
For example, Yunnan Baiyao had been developed in 1902 by Qu Huangzhang and is widely used in wounds, rhexis hemorrhage, gynecological bleeding disorders, and chronic stomach disease because of its antihemorrhagic hemostatic, wound healing, and pain-relieving properties [
44].
According to previous publications, Yunnan Baiyao exerts its hemostatic effects by promoting platelet aggregation; shortening the coagulation, bleeding, and prothrombin times; accelerating blood vessel growth and connective tissue proliferation to achieve the effect of healing wounds; lowering blood viscosity and accelerating blood flow in the microcirculation to eliminate blood stasis; demonstrating significant anti-inflammatory action by accelerating glucocorticoid secretion; decreasing blood vessel permeability and inflammatory mediator release; promoting the marrow mesenchymal stem cell proliferation; and enhancing osteoblast activity and new blood vessel formation leading to improved blood supply and bone fracture repair [
45]. Furthermore, Yunnan Baiyao is reported to still possess antibacterial capacity and analgesic activity [
46].
Yunnan Baiyao entails several forms of preparation (powder, capsule, aerosol, emplastrum, and tincture) for local and oral application [
47]. Increasing innovative preparation forms of Yunnan Baiyao will be developed to elevate patients’ compliance. Meanwhile, further research on the mechanism(s) of Yunnan Baiyao’s unique, reliable curative effects is being conducted to guide novel and safe clinical use.
Industry of ethnomedicines
According to a statistical analysis, China currently has 154 enterprises for ethnomedicine production, which are mainly distributed in Yunnan, Tibet, Guizhou, and Qinghai. These enterprises include 42 enterprises for Tibetan ethnomedicine production, 6 enterprises for Mongolian ethnomedicines, 9 enterprises for Uygur ethnomedicines, 11 enterprises for Dai ethnomedicines, 13 enterprises for Yi ethnomedicines, and 73 enterprises for Miao ethnomedicines [
9], resulting in the production of a total of 7 categories and 906 varieties of patent ethnomedicines. The dosage forms include tablet, capsule, powder, granule, and pill. The industry of ethnomedicines is developing very rapidly. In 2006–2009, the enterprises for ethnomedical production in China yielded 22.46 billion yuan, providing 1.26 billion yuan as value added tax [
48]. In 2009, the total sales of ethnomedicines in China were approximately 14 billion yuan. In 2010, the total sales reached 15.5 billion yuan [
9]. In 2013, the sales of Miao ethnomedicines in Guizhou Province reached 15 billion yuan [
49]. To provide an example of the annual sale revenue of some well-developed ethnomedical companies in 2015, we present the sales revenue of Yunnan Baiyao Group Co., Ltd. at 20.74 billion yuan, revealing an increase by 10.22% in the previous year [
50]. Meanwhile, the sales revenue of Guizhou Yibai Pharmaceutical Co., Ltd. reached 3.30 billion yuan, demonstrating an increase by 4.61% over the previous year [
51].
At the same time, the industry system of ethnomedicines has gradually formed and improved itself. The raw material supply was gradually modified from a strict dependence on natural resources to large-scale cultivation in strict compliance with good agricultural practices (GAP). Patented medicine production gradually transformed from traditional workshops to modern professional manufacture in strict compliance with good manufacturing practice (GMP). Supply gradually transformed from the sale of drugs by “roving doctors” practicing medicine to the gradual establishment of a drug distribution system in strict accordance with good supplying practice (GSP). Numerous ethnomedical brands have emerged, and these brands include not only the nationally known traditional ethnomedicines, such as Yunnan Baiyao (Yi ethnomedicine), Cheezheng (Tibetan ethnomedicine), Mengwang (Mongolian ethnomedicine), and Qikang (Uygur ethnomedicine), but also newly emerging ethnomedicines, such as Bailing, Yibai, and the “
Erigeron breviscapus” series for Miao ethnomedicine. Many provinces have considered ethnomedical production as a pillar industry and a new economic growth point [
52,
53].
Problems and countermeasures in the development of ethnomedicines
To further accelerate the progress of ethnomedicine, we identified the main problems associated with the current development of China’s ethnomedicines as follows: lack of dedicated, national-level laws and regulations for ethnomedical management; incomplete system of discipline; low overall level of theoretical and applied development; insufficiently strong normalization; low societal awareness; gradual weakening or near disappearance of traditional application experience with loss of intellectual property; decrease in wild medicinal resources in the ethnic regions; and threatened extinction of some medicinal species [
54–
57].
To resolve the aforementioned current problems in ethnomedical development, researchers have suggested the strengthening of ethnomedicines to fill the gap in the regulatory system of ethnomedicines and standardize ethnomedical management. The scholars also suggest the need to investigate the supporting policies related to ethnomedicines. A scientific, reasonable, and relatively comprehensive disciplinary system of ethnomedicines should be established as soon as possible. In addition, modern research of ethnomedical theory should be strengthened, and a standardized research platform for ethnomedicines should be established. The exploration, collation, and systematic upgrading of ethnomedicines should be further promoted, industry-wide awareness of intellectual property protection should be promoted, and an intellectual property protection system for ethnomedicines should be established and improved. Moreover, studies on the ethnomedicine resources protection and the standardized ethnomedicines planting should be strengthened to ensure the healthy and sustainable development of ethnomedicines [
58–
60].
Exploration of the innovative development path for ethnomedicine
Ethnomedicines are based on the collective wisdom and long-term practice of ethnic minorities, which results in advantages in efficacy, safety, accessibility, and affordability, thereby creating a vast space for their own development. Ethnomedical development is not only an important medical and academic topic but also a key issue concerning the respect of ethnic sentiment, the heritage of ethnic culture, the enhancement of ethnic unity, and the promotion of national prosperity. Since the founding of P. R. China, the joint efforts of relevant departments and agencies, including governments and research institutes as well as ethnomedicine companies, have greatly accelerated the development of ethnomedicines. Ethnomedicines of more than 30 ethnic minorities have been explored, protected and developed, and some of these ethnomedicines form part of the modern industry.
Yunnan is China’s border province with the most minorities. The area holds most abundant biological diversity and ethnic cultural diversity in China. Nearly all of the 25 ethnic minorities in this province hold their own theory of traditional medicines or medication experience. Based on this unique advantage, we proposed a research mode of “close integration of basic research and applied development,” implemented a systematic project of innovative research and applied development of ethnomedicines, and explored a practical development path for ethnomedicines (Fig. 1). A systematic study of the application experience and medicinal resources of ethnomedicines is performed to explore new sources, standardized development research on the efficacy, safety, preparation, quality control, and clinical efficiency of ethnomedicines are conducted. Achievements are successfully industrialized with an effort placed on their internationalization. Notably, platform establishment and team training are always important in ensuring innovative development. Once research studies achieve economic interest through industrialization, support can be returned to basic research and the research and development (R & D) platform can be enhanced, thereby promoting sustainable ethnomedical development.
The systematic project implemented for innovative research and applied development of the ethnomedicines has yielded a series of major innovative results that are basic, nonprofit, and original through resource study. With the traditional medication theory or experience of ethnomedicines obtained during the resource study as clues, in combination with multidisciplinary drug screening and evaluation, the Erigeron breviscapus series products of Miao ethnomedicine as well as the Gold® series of Yi ethnomedicine have been developed and successfully industrialized and have achieved good economic results. The R & D platform, which includes a state-certified drug safety evaluation center and an innovative team, has been established and observed to exert an increasing effect on the industry. The series of notable achievements described above and their wide application in the industry are important for ethnomedical development and the social progress of minority areas. Such advances also fully confirm the feasibility and practicability of the innovative development path of ethnomedicines, which may serve as a reference for the healthy and sustainable development of ethnomedicines.
Concluding remarks
In December 2015, Professor Youyou Tu, Nobel Laureate in Physiology or Medicine, mentioned in her speech entitled “Artemisinin, Gift from Traditional Chinese Medicine to World” that “Chinese medicine and pharmacology are a great treasure house, which should be explored and raised to a higher level.” This idea was introduced by Mao Zedong in the 1950s. In the 1970s, Chinese scientists identified key information from the literature of the Eastern Jin Dynasty and thus successfully discovered artemisinin. The process behind the discovery of artemisinin has become a model for “exploring” and “raising” the treasure house of traditional Chinese medicine. After a lapse of nearly half a century, the Nobel Committee declared that the 2015 award should be given to a “person inspired by traditional medicine.” The Chairman of the Committee believed that traditional Chinese herbal medicines could provide new scientific inspiration. Jan Lindsten, who is the former Secretary-General of the Commission, stated that efforts are “extremely important and well worth to pursue in the future to find treasure from traditional Chinese medicine in developing new drugs.” The “Traditional Chinese Medicine Development Strategy Plan (2016–2030)” released in February 2016 by the State Council of China describes the positive effects of traditional medicines on an entire society and individual lives and emphasizes the “unique health resources, potent economic resources, and scientific and technologic resources with the advantages of originality, excellent cultural resources, and important ecological resources” of traditional medicine. The plan places a top priority on the inheritance and innovation of traditional medicine. Traditional medicines, which have been applied for thousands of years and have been repeatedly tested and improved through clinical practices, will continue to play a unique role in human health and economic and social development.
We found that the discovery of artemisinin was highly similar to that of quinine, a traditional antimalarial drug discovered in 1820, and to that of other drugs, such as aspirin and morphine. These drugs were identified on the basis of previous practices that revealed the specific therapeutic effects of certain plants. Relevant knowledge and experience already existed and were inherited in the form of written or oral literature. However, these drugs provided actual benefits to humans only after modern methods were applied to extract certain active ingredients, followed by strictly controlled scientific analysis and evaluation, production of appropriate preparations, and transformation to drugs with clear safety features and efficacies. As such, the members of the Nobel Committee well justified the awarding of the Nobel Prize to Professor Tu because of her efforts to employ “applied modern technology” to “identify the specific compound in traditional Chinese medicines,” and this compound is “very unique.” Therefore, innovating and developing traditional medicines should not only fully consider traditional knowledge and experiences but also follow modern theory, introduce modern science and technology, and focus on safety, effectiveness, and quality control. The significance of this initiative lies not only in inheriting tradition but also in explaining and improving the rationality of traditional applications to satisfy the health care needs of current societies.
Higher Education Press and Springer-Verlag Berlin Heidelberg
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