Tribute to the third anniversary | Interpretation of academician expert report: Research and Application of Frontier Omics of Chinese Materia Medica b
Source:DUZHENG Release date:2019-03-06
Chinese materia medica (CMM) is an important health resource in China. Under the background of the Healthy China strategy, the big health industry of CMM has ushered in unprecedented development opportunities. With the promulgation of laws and regulations such as Some Opinions on Supporting and Promoting the Development of Traditional Chinese Medicine Industry, Strategic Outline for the Development of Traditional Chinese Medicine (2016-2030) and Law of the People’s Republic of China on Traditional Chinese Medicine, the development of traditional Chinese medicine (TCM) has been included in the national strategy, greatly broadening the market prospects.
The quality of CMM is the key to ensuring the efficacy and safety of TCM and it is an important link restricting the modernization of CMM industry. At the “Biomedical Industry Development Summit” of the Third Anniversary Celebration of Duxact, Professor Chen Shilin, Expert Consultant at Duxact, Academician at International Eurasian Academy of Sciences (欧亚科学院) and Director of Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences (中国中医科学院中药研究所), was invited to give a special report named Research and Application of Frontier Omics of Chinese Materia Medica.
The report is explained in detail below.
Fine cultivation of pollution-free Chinese medicinal materials is a “good medicine” to ensure the healthy development of Chinese medicinal materials industry.
Professor Chen pointed out that the control bottleneck of CMM quality originated from the identification and planting of Chinese medicinal materials. The pesticide residues and heavy metal content are key indicators for the quality control of CMM, which are directly related to the quality and affect the safety and efficacy of CMM. After entering the body, excessive pesticides cause liver and kidney toxicity, cancer, fetal malformation, infertility, and even death, which seriously endangers human health. Academician Zhong Nanshan once asserted, “If residual pesticides are not controlled anymore, Chinese people will not be able to produce children in 50 years.” The problem of pesticide residues has been valued highly by the state and the industry, and the formulation of standards for harmful residue limits of Chinese medicinal materials has been listed as a priority for the revision of quality standards for Chinese medicinal materials and decoction pieces in 2020 version of Chinese Pharmacopoeia. In addition, the deterioration of planting environment and the nonstandard production are the reasons for the decline in the quality of Chinese medicinal materials. Some media commented that “the traditional Chinese medical science with thousands of years of history will be ruined by the quality of Chinese medicinal materials.”
On the occasion of the crisis of Chinese medicinal materials quality, Professor Chen's team proposed to build a system of fine cultivation of pollution-free Chinese medicinal materials, and to crack the excessive heavy metals, pesticide residues and irregular planting of Chinese medicinal materials and other maladies from the source. We should set up a molecular marker-assisted breeding system for new stress-resistant varieties based on omics, adopt the herbgenomics technology to determine the genome map of Chinese medicinal materials, build a national gene pool of CMM, apply DNA markers to screen out key markers based on target characters, assist the selection and breeding of characteristic strains, optimize stable characters, and form drought tolerant, pest resistant and high-yield high quality varieties. So far, the molecular marker-assisted breeding system for new stress-resistant varieties based on omics has analyzed 122 genetic maps of Chinese medicinal materials, which has laid the foundation for molecular breeding; established a national engineering laboratory for the breeding of endangered medicinal materials, which has provided a technical platform for the breeding of stress-resistant varieties. The high-quality genes of Chinese medicinal materials such as salviae miltiorrhizae, ginseng, Chinese prickly ash, notoginseng, purple perilla, and artemisia annua were marked. The incidence of pests in the new variety of notoginseng was reduced by 62%. The production of Zhongyanfeisu, a new variety of purple perilla was increased by two times. The content of artemisinin in Yanqing No.1, a new variety of artemisia annua, was as high as 2.1%. We should establish a comprehensive prevention and control technology system for diseases and pests in pollution-free Chinese medicinal materials, and use DNA barcode, qPCR and soil metagenomics techniques to build a soil-borne disease field identification system to discover the pathogenic pests and pathogenic bacteria of notoginseng. We should take measures such as soil composite improvement, green manure returning to the field, and fine regulation of fungicides to comprehensively transform the soil. The biological pest control measures developed with the idea of “controlling pests and resisting diseases with bacteria” reduce the use of pesticides and fertilizers, with remarkable effect and safety. We should establish a fine operational process for field comprehensive agronomy, improve the soil to increase the soil fertility, limit chemical pesticides and establish regulations on field production and standard processes for agricultural control. A general standard system should be developed for pollution-free Chinese medicinal materials, setting a good example for high-quality Chinese medicinal materials.
At present, the production practices and quality standards for 150 non-polluted Chinese medicinal materials such as notoginseng, ginseng and fritillariae cirrhosae bulbus have been formulated and released. A total of 215 planting sites have passed GAP or GACP certification to ensure the safety and reliability of Chinese medicinal materials. In addition, the constructed system for the pollution-free fine cultivation and production of notoginseng was promoted and implemented in Yunnan. It received wide attention from multiple media outlets such as www.zhzyw.com, www.yunnan.cn, and www.chinanews.com as well as all sectors of society. The promotion of pollution-free cultivation system of Chinese medicinal materials has also passed the summary acceptance and received high attention from experts and many well-known domestic media, which indicates that the pollution-free cultivation system and production system of Chinese medicinal materials promote the production of medicinal materials to enter into the “pollution-free era.” The standards for pollution-free Chinese medicinal materials have established industry norms to ensure the healthy development of Chinese medicinal materials industry.
Professor Chen also used the herbgenomics technology to conduct in-depth research on various Chinese medicinal materials such as chrysanthemum, andrographis, selaginella tamariscina, ginseng and ganoderma lucidum, screened and cultivated drought tolerant, pest resistant and high-yield high quality new varieties, and promoted the related research of biosynthesis of andrographolide and ginsenoside. The established medicinal model of ganoderma lucidum biological system has broken through the bottleneck of the lack of model organisms in the research of CMM. The results were published in Nature Communications and were specially reported by FEATURED IMAGE, Nature China, USA TODAY and other media. It is believed that ganoderma lucidum is a satisfactory model system that studies the secondary metabolism pathway of CMM and its regulation.
DNA barcode identification system for Chinese herbal medicines leads the revolution of Chinese herbal medicine identification
According to statistics, there are 11,146 kinds of Chinese medicinal materials in China. In the seven domestic markets of Chinese medicinal materials, about 4.2% of 1,436 medicinal materials are counterfeit, 43 swertiam mussotii franch products are chaotic, and 60% of commercial rhodiola rosea is adulterated, which indicates that the varieties of Chinese medicinal materials in China are very chaotic. The data from National Institutes for Food and Drug Control (中检院) showed that 36% of the Chinese medicinal materials were unqualified. The misuse of caulis aristolochiae manshuriensis vs. akebiae caulis and aristolochia fangchi vs. radix stephaniae tetrandrae caused severe acute kidney disease. This was named the most serious herbal medical event in the world. The reason is that the varieties of Chinese medicinal materials are complex and diverse, and the counterfeits and adulterants are uneven and cannot be identified. Traditional Chinese medicinal plant identification methods such as macroscopic identification, origin identification, microscopic identification, and physical and chemical identification have technical limitations and still cannot completely and accurately identify Chinese medicinal species.
Faced with the dilemma of CMM identification methods, Professor Chen creatively introduced the concept and theory of “Herbgenomics” into the identification of Chinese medicinal materials. The herbgenomics is a frontier discipline that studies CMM and its role in human body at the genome level. It uses the omics technology to study the genetic information of the original species of CMM and its regulatory network, and clarifies the molecular mechanism of CMM in preventing and treating human diseases. Herbgenomics is a bridge between traditional and modern herbs. The team collected a large number of Chinese medicinal species and united a number of statutory drug control institutions to find and verify that the ITS2 sequence can be used as a universal DNA barcode sequence for CMM. The identification of Chinese medicinal species is accurate, stable, efficient and more objective. Also, it was found that ITS2 can be used to study the grades of Chinese medicinal materials and genuine medicinal materials, to identify Chinese herbal medicines and adulterants, to guide the construction of CMM quality standard system and to cultivate Chinese medicinal species with superior quality. The team focused on the identification and study of CMM DNA barcode, and published ITS2 as a Universal DNA Barcode Sequence for Medicinal Plants, DNA Barcode Identification System for Chinese Herbal Medicines, Nuclear Genome Sequence Analysis, Plant Barcode Research from Gene to Genome, Core Barcode of ITS/ITS2 Seed Plants and many other high-level papers, among which, once published, ITS2 as a Universal DNA Barcode Sequence for Medicinal Plants caused an international academic sensation, has been cited more than 789 times, and was selected as one of the 16 articles that attracted the most attention in the ITS2 field in recent 25 years by German professional websites. Up to now, five of the top ten papers in the field of international medicinal plant barcodes are compiled by Professor Chen’s research team, which means that China is leading the way in the field of DNA barcode research of medicinal plants. The research results of CMM DNA barcode identification were included in the Top 10 News of World Traditional Chinese Medicine (WFCMS 2014), and rated as China Top 10 Medical Research Progress in 2016. It also won the second prize of National Science and Technology in 2016, and the first prize of international contribution scientific and technological progress for traditional Chinese medicine of WFTCM in 2018. These marked that the identification of Chinese medicinal materials entered into an era of universal, standardized genetic identification.
Based on the research of ITS2 as a universal DNA barcode sequence for CMM, the team created a DNA barcode identification system for Chinese herbal medicines from the aspects of Chinese medicinal materials identification system composition, standard operation procedure establishment, Chinese herbal species identification database platform construction and identification software system development, and realized the standardized identification using Chinese herbal medicine “Gene Identification Card.” At present, China’s identification system has been included in the Chinese Pharmacopoeia, and the drug regulators in developed countries or regions such as the United Kingdom, the United States, Japan, and South Korea have also introduced DNA identification for herbal medicines. According to Professor Chen, the DNA identification system for Chinese herbal medicines has been applied by 1,230 units at home and abroad, such as national statutory inspection agencies, scientific research institutes, universities, medicinal materials circulation, production enterprises and hospitals, indicating that the system can be widely used in the processing, production, circulation, research and other links of Chinese medicinal materials source, provide comprehensive protection for the identification of Chinese medicinal materials, and help to improve the quality of CMM industry.