Traditional Chinese medicine (TCM) is considered as a unique treasure of Chinese civilization for its profound theoretical system and extensive experience in clinical practice for more than two thousand years. As one of the most commonly used folk medicines, Chinese medicines have made indelible contributions to well-being maintenance and disease treatment, as well as the progress of human civilization . Now TCM is used not only in China, but also used as an alternative medicine in most Western countries. In recent decades, amid the increasing demand of both international and Chinese consumers, the growing gap between the market demand and supply of Chinese medicines has been seen . It is well-known that a large number of Chinese medicine raw materials are produced in China, while a huge proportion of them is directly collected from the wild. Previous studies indicated that the resource of wild medicinal plants is decreasing by approximately 30% per year, while the resource of some medicinal animals (such as Pilose Antler, Syngnathus, Rhinoceros Horn, and Tiger Bone) has become extinct or on the verge of extinction . Moreover, some of wild medicinal plants and rare medicinal animals have been listed in the Convention on International Trade in Endangered Species of Wild Fauna and Flora . The scarcity of natural sources and the rapidly increasing demand result in the extremely high prices of these rare species on the market.
The big gap between the market demand and supply of Chinese medicines (especially for rare and precious species) has severely impaired the integrity and sustainability of TCM. On one hand, some rare and precious Chinese medicines (such as wild Ginseng, Ganoderma lucidum, Dendrobium officinale, and Bezoar) are often used as a key material or an essential part of TCM prescriptions, owing to their inherent advantages including unique therapeutic efficacy, low toxicity and the irreplaceable roles in health preservation and disease treatment . On the other hand, there are no suitable and effective substitutes for most rare medicinal materials at present. Taking bear bile for example, this precious medicinal powder has been used for thousands of years for curing hepatic and biliary disorders, cardiovascular and cerebrovascular disorders, pulmonary disorders, fever and ophthalmological disorders . However, there is currently no suitable artificial substitute available on the market to replace this precious medicine. Similarly, Cordyceps sinensis (a precious Tibetan medicine) exhibited multiple health-promoting effects (such as immune regulatory effects) and is currently used for tonifying the kidneys, soothing the lungs, stopping blood bleeding and eliminating phlegm [7-8], but this rare medicine is also hardly replaced by other common medicinal materials.
To better solve the supply crisis of rare medicinal materials, it is urgent and necessary to find suitable substitutes for those frequently used precious Chinese medicines. Over the past few decades, great efforts have been made by researchers to find feasible solutions to the resource shortage of some important precious medicinal materials, which is very helpful for the sustainable use of Chinese medicines. Generally, there are several ways to realize the sustainable utilization of the endangered and rare medicinal plants. One is cultivation of the varieties with high-quality and high-yield to replace wild rare medicinal plants, with the help of a variety of modern agricultural techniques including molecular breeding, artificial propagation, large-scale artificial cultivation, as well as scientific harvesting and processing . Currently, large-scale cultivation and plantation strongly facilitate mass production of some important rare medicinal materials including Ren Shen (Ginseng Radix et Rhizoma), San Qi (Notoginseng Radix et Rhizoma), Shi Hu (Dendrobii caulis) and Bing Pian (Borneolum Syntheticum), resulting in significant price reduction. Another way is to find some closely related species of rare medicinal plants with similar chemical profiles and pharmacological functions. For example, ZHANG et al.  found that artificially cultivated Wabu Bei Mu (Fritillaria Unibracteata Hsiao et K.C. Hsiavar Wabuensis) was used as a substitute for valuable Song Bei Mu (Fritillaria Sungbei Hsiao et K. C. Hsia) to treat dry coughing caused by lung heat. The additional choice is to expand the medication part from a single part to the whole plant. For example, the root of San Qi (Notoginseng Radix et Rhizoma) is traditionally used as a herbal medicine but now the whole plant has been approved for clinical use , while both the fruit and flowers of Rou Gui (Cinnamomi Cortex) can also be used as herbal medicines in addition to its traditionally used parts (bark and twig) .
Compared with medicinal plants, endangered medicinal animals are facing bigger threats and challenges because of their longer breeding cycle, stricter requirement in habitat environment and more difficulty in artificial breeding and domestication . More importantly, the ethical and biosecurity issues, as well as animal welfare concerns are making the resource shortage of medicinal animals even worse for the TCM industry. Thus, there is an urgent need to seek the substitute products for replacing endangered medicinal animals. Owing to the serious resource shortage of endangered medicinal animals, some TCM companies have been forced to choose less expensive animal species with similar chemical constituents and pharmacological actions for making TCM products that contain the materials from endangered medicinal animals. This alternative strategy can protect endangered animals to the greatest extent, and has been widely accepted by the industry and the market. For example, LIU et al.  found that goat horn can be used as a substitute for Saiga antelope horn to exert analgesic and antipyretic effects, while plateau zokor bone has been used as a substitute for replacing tiger bone to treat osteoporosis . Artificial breeding of rare medicinal animals is another feasible way for sustainable use of medicinal animal resources . Currently, China has successfully realized large-scale production of velvet antler by artificial breeding of sika deer and red deer, along with artificially cultured pearls and bezoars. There is another promising and effective way to address this issue, namely, using single or multiple active ingredients to replace rare animal products for preparing novel Chinese medicines . Such strategy can fundamentally solve the shortage crisis of rare medicinal animal resources, and does not require large-scale and labor-intensive breeding of animals. Meanwhile, the use of unique active ingredients as raw materials for preparing Chinese medicines can avoid many common problems of animal medicinal materials, such as bing perishable, difficult to store, strict inspection and quarantine, as well as difficult in carring out quality control. Today, artificial musk, artificial bezoar and artificial bear bile have been successfully developed by researchers through chemical or biological synthesis, while part of them have been used to replace the animal-derived medicinal products to make the low-cost and high-quality innovative TCM products accessible to the public. Notably, since the artificial musk was approved for marketing in 1994, this artificial product has been used to produce more than 400 kinds of TCM prescriptions, while the cumulative sales of related TCM products are more than five billion yuan  (Fig.1).
Currently, some varieties of precious Chinese herbal medicines and artificial substitutes for rare animal medicines have been mass-produced by a panel of agricultural and chemical techniques. Consequently, the market prices of these substitutes are much lower than that of wild Chinese medicines (as shown in Table 1).
Chinese medicine Price of
wild type (¥/kg)
Price of artificial
Fold Main functions Ginseng 13000 360 36.1 Invigorates vitality, reinforces the spleen and benefits the lung Ganoderma lucidum 260 45 5.8 Tranquilizes the mind, nourishes the lungs and boosts qi Borneol 1200 160 7.5 Tranquilizes the mind, clear heats and alleviates pain Dendrobium officinale 800 75 10.7 Tonifies the stomach, increases fluids, nourishes yin and clears heat Cistanche 550 120 4.6 Tonifies the kidneys and relieves constipation Edible tulip 1800 240 7.5 Clears heat, removes toxins, reduces phlegm and relieves cough Tabasheer 600 40 15 Clears phlegm and prevents shock Pilose antler 2400 280 8.6 Tonifies the liver and kidneys, and strengthens muscles and bones Syngnathus 13500 1000 13.5 Tonifies the kidneys, warms yang, reduces swelling and resolves masses Agkistrodon 100 18 5.6 Clears heat, removes toxins, circulates blood and resolves stasis Bezoar 550000 800 687.5 Reduces swelling, resolves masses and clears heat from blood *The market price was provided by Bozhou TCM market, Anhui Province, in March, 2022.
Table 1. The market prices of some rare and precious Chinese medicines and their artificial substitutes
Although artificial substitutes of precious medicinal materials have achieved great success over the past decades, it should be noted that there are still some differences in both chemical composition and pharmacological effect between wild medicinal materials and their artificial substitutes. For instance, extensive studies have demonstrated that the total content of the ginsenosides in wild ginseng is significantly higher than that in cultivated ginseng or the ginseng under forest, which well explains the difference in clinical efficacy between wild ginseng and cultivated ginseng . To obtain high-quality medicinal materials, agricultural scientists and cultivation experts are trying to find feasible strategies for improving the contents of “unique active ingredients” in cultivated plants, through improving the planting and processing techniques or cultivating new varieties which are rich in “unique active ingredients” and more suitable for artificial cultivation.
In future, more strategies and in-depth investigations should be used to seek and develop more practical artificial substitutes for replacing precious Chinese medicines, which will provide a sustainable way for utilizing precious and rare Chinese medicines, as well as benefit the quality control and globalization of animal derived TCM products. In addition to large-scale artificial planting of medicinal plants and breeding of medicinal animals, seeking unique active ingredients in rare Chinese medicines and determining the best combinations of ingredients as artificial substitutes to replace precious Chinese medicines deriving from wild plants or animals can fundamentally solve the resource crisis of medicinal plants and animals. There are several suggestions to improve the efficacy for seeking unique active ingredients in rare Chinese medicines and developing more useful artificial substitutes. First, the unique active ingredients in rare medicinal plants or medicinal animals should be identified and validated by a variety of modern techniques , while the pharmacological uniqueness, irreplaceability and clinical efficacy of the unique active ingredients should be studied in-depth. Second, it is necessary to develop highly efficient synthetic/biosynthetic schemes of the unique active ingredients in rare Chinese medicines using a panel of state-of-the-art techniques for green chemical and biological synthesis . Especially, the highly efficient and environmentally friendly schemes for producing target active ingredients are always desirable. Third, the clinical efficacy, safety profiles and drug-likeness of the unique active ingredients or their combinations should be systematically investigated , determining the best choice as the major constituent(s) for preparing the artificial substitute product that display equivalent or better clinical efficacy and safety profiles. Notably, the research and development of practical substitutes of rare Chinese medicines is a systematic project, which needs the joint efforts of the government, the medicine industry and the academia. For some extremely scarce medicinal materials with large market demand, it is highly recommended that the government and enterprises should set up special foundations to support the researchers and scientific research groups to overcome the key scientific issues and core technical problems in this field.
Sustainable utilization of precious Chinese medicines: challenges and the road ahead
- Received Date: 2022-05-20
- Available Online: 2022-11-20