Overview of Research Trends in Precious Chinese Medicines

Introduction Traditional Chinese medicine (TCM) has continued through centuries to this day since the ancient times and has contributed greatly to the well-being maintenance and disease treatment in China.[123] Before the ushering in of Western medicine into China in the 19th century, TCM had been the major healthcare and medical modality in Chinese communities.[4] This ancient art of healing has not diminished over time; conversely, it is now widely accepted by patients both in China and around the world owing to the shift of the disease spectrum and the rise of the “return to nature” paradigm. Moreover, TCM is attracting increasing attention from research circle worldwide.[5] At present, TCM is used in approximately 45% of the world's countries, and a large amount of Chinese medicine raw materials is exported from China, and some of these Chinese medicines are collected directly from the wild.[67] Owing to the popularity of Chinese medicine around the world, the natural resources required for Chinese medicine production can hardly meet the rapidly increasing demand. Wild herbal resources are decreasing by approximately 30% every year.[589] For some “precious Chinese medicines,” such as Ren Shen (人参 Ginseng Radix et Rhizoma), Ling Zhi (灵芝 Ganoderma), Xue Lian (雪莲 Saussureae Involucratae Herba), Fan Hong Hua (番红花 Stigma Croci), Jin Xian Lian (金线莲 Anoectochilus roxburghii), Xiong Dan Fen (熊胆粉 Ursi Fellis Pulvis), Tie Pi Shi Hu (铁皮石斛 Dendrobium officinale), and Dong Chong Xia Cao (冬虫夏草 Cordyceps), the problem of the scarcity of wild resources is particularly serious, largely because of the destruction of natural habitats and overexploitation by humans. Some of these species are currently listed in the Convention on International Trade in Endangered Species of Wild Fauna and Flora.[1011] These herbs are traded at extremely high market prices because of their scarcity, sometimes merely based on speculation. Although the emergence of cultivation and natural fostering techniques and the application of substitutes for some precious Chinese medicines in recent years have played an important role in resource conservation, the keen demand for precious Chinese medicines continues unabated.[11] Sustainable utilization of precious and rare Chinese medicine resources remains a great challenge. The special issue published in Chinese Medicine and Culture provides a valuable summary on several precious Chinese medicines that have high market value and possess good clinical usage. The precious Chinese medicines discussed in this special issue include Zang Hong Hua (藏红花 Stigma Croci), Huang Jing (黄精 Polygonati Rhizoma), Huang Qi (黄芪 Astragalus membranaceus), Dong Chong Xia Cao (冬虫夏草 Cordyceps), Shan Ci Gu (山慈菇 Pseudobulbus Cremastrae seu Pleiones), Rou Gui (肉桂 Cinnamomi Cortex), Chen Xiang (沉香 Aquilariae Lignum Resinatum), and Jin Chai Shi Hu (金钗石斛 Dendrobium nobile Lindl). In this highlight, we provide brief overviews of their history, current usage, therapeutic efficacy, and pharmacological actions. Summary of the Precious Chinese Medicines Included in this Special Issue Stigma Croci is an autumn-flowering perennial plant. The earliest use of Stigma Croci in TCM was recorded in the Gang Mu Shi Yi (《纲目拾遗》 Supplement to the Compendium of Materia Medica) during the Tang dynasty (741 A.D.). It has been globally recognized as one of the most expensive medicinal plants and the best dye substance since the ancient time. Stigma Croci was initially used as a precious spice for the royal family and noble officials and was later used as a valuable gynecological medicine in TCM.[12] Historically, China relied on imported Stigma Croci till the 20th century. In 1979, a Shanghai medicinal materials company imported 0.5 tons of Stigma Croci from Japan and successfully cultivated it in Ma Qiao town of Shanghai by combining the technology of cultivating corms in open fields but producing flowers indoors. Starting in 1987, China began to export Stigma Croci. After the 1990s, China made great progress in Stigma Croci cultivation and research, which resulted in expanding of the planting area. Stigma Croci is currently being cultivated in more than 20 provinces and cities in China, mainly in Tibet, Shanghai, and Zhejiang. Over 90% of China's total yield of Stigma Croci is harvested from Chongming District of Shanghai. Recent studies have identified the major bioactive compounds in Stigma Croci and various biological properties, including anti-cancer, anti-bacterial, anti-inflammatory, anti-nociceptive, hypnotic, anxiolytic, anesthetic, anti-depressant, and bronchodilatory effects.[13141516] In addition to serving as a Chinese medicinal herb, Stigma Croci is currently used in the industries of food, dye, and perfume. Polygonati Rhizoma is one of the most popular Chinese medicines used in a dried form. It was first documented in the Ming Yi Bie Lu (《名医别录》 Miscellaneous Records of Famous Physicians) in China.[17] In the Zhong Guo Yao Dian (《中国药典》 Chinese Pharmacopeia) version 2020, Polygonati Rhizoma is stated to have the effects of replenishing qi, nourishing yin, invigorating the spleen, moistening the lungs, and strengthening the kidneys. Polygonati Rhizoma was originally used as a food for Taoist fasting (Bigu), which is regarded as a good strategy for resisting various chronic diseases such as diabetes and hyperlipidemia.[18] In Taoist medicine, Polygonati Rhizoma is regarded as an edible herb with little toxicity and few side effects. It is believed to improve one's appearance and prolong life. Pharmacologically, Polygonati Rhizoma has diverse therapeutic actions, including anti-oxidant, anti-diabetic, anti-osteoporosis, anti-cancer, anti-microbial, anti-hyperlipidemic, cardiomyocyte protection, immunomodulatory function, effects against infertility, and enhancement of sleep and memory.[17192021] Astragalus membranaceus (A. membranaceus) is a major tonic used in TCM practice. The medicinal use of this herb was first recorded in the Shen Nong Ben Cao Jing (《神农本草经》 Shennong's Classic of Materia Medica), which was written approximately 2000 years ago.[22] A. membranaceus is commonly used in TCM to treat anemia, wounds, fever, allergy, fatigue, loss of appetite, and abnormal menstrual bleeding.[23] At present, A. membranaceus is often prescribed with other herbs to treat a broad spectrum of diseases, such as diabetes, cirrhosis, leukemia, nephritis, viral infections, and cancer, without any side-effect trace of toxicity. In addition, A. membranaceus can enhance immunity, protect the liver, and possesses anti-aging, anti-stress, and anti-bacterial properties. More than 200 compounds have been identified and isolated from A. membranaceus. These compounds, which can be grouped into three main chemical classes, namely flavonoids, polysaccharides, and saponins,[24] are the major driving forces behind the diverse biological and pharmacological activities of Astragalus species.[25] Most notably, Cordyceps refers to Ophiocordyceps Sinensis (O. sinensis). It a naturally occurring fungus-caterpillar complex that has been used in TCM and traditional Tibetan medicine since the 15th century. It is also known as “Dong Chong Xia Cao” (冬虫夏草) in Chinese, which means the mixture of “worm in the winter, herb in the summer.”[26] It is used to strengthen the immune system, assist the lung yin, stop bleeding, transform phlegm, and cure low libido and impotence by correcting yang deficiency in TCM. O. sinensis is highly regarded as a precious Chinese medicinal tonic because it can only be harvested from remote locations, usually at altitudes exceeding 3800 m in Tibet, Qinghai, Yunnan, Sichuan, and Gansu provinces in China.[27] Owing to its limited quantity and high demand, O. sinensis is commercially cultivated for a short growing cycle and low cost. Both natural and cultivated O. sinensis contain bioactive compounds that are believed to confer therapeutic effects. Cultivated O. sinensis can be a good substitute for naturally occurring Ophiocordyceps because it contains higher amounts of cordycepin and a lower risk of contamination than its natural counterpart. However, the active compounds in cultivated O. sinensis responsible for its therapeutic effects require rigorous testing through randomized placebo-controlled trials to clarify their clinical efficacy. Pseudobulbus Cremastrae seu Pleiones was first listed as a precious Chinese medicine in the Ben Cao Shi Yi (《本草拾遗》 Supplement to Materia Medica) during the Tang dynasty.[28] According to the Chinese Pharmacopoeia, it is derived from the pseudobulbs of three orchidaceous plants, namely Cremastra appendiculata (D. Don) Makino, Pleione bulbocodioides (Franch.) Rolfe, and P. yunnanensis Rolfe. It has attracted the attention of researchers because it is commonly prescribed in TCM for the treatment of various cancers, bacterial infections, burns, and frostbite.[29] However, most studies on the biological activities of Pseudobulbus Cremastrae seu Pleiones were based on in vitro bioassays. In vivo studies should be conducted in the future to discern the bioactivities and associated molecular mechanisms of this herb. Cinnamomi Cortex is a famous Chinese herb, and the source of this herb is the bark. Its medicinal use has long been recorded in the Chinese Pharmacopoeia. The genus Cinnamomum of the family Lauraceae contains more than 250 species,[30] and each of them has specific morphological characteristics and a unique phytochemical composition.[3132] Clinical studies that used Cinnamomi Cortex as an intervention revealed that supplementation at a dose as low as 1g/day could improve hemoglobin A1c levels in patients with poorly controlled diabetes. There is a dose-response relationship concerning postprandial blood glucose modulation, in which at least 5g of crude cinnamon appeared necessary for blood glucose control in healthy or prediabetic people; however, this dose-response relationship was not observed in the type 2 diabetes group. Prolonged supplementation with cinnamon might improve insulin sensitivity. Future studies on cinnamon should pay attention to such matters as the species and form (e.g., powdered, extract) of cinnamon. Aquilariae Lignum Resinatum is a dark resinous substance found in the trunk of wounded Aquilaria plants. Known as “Chen Xiang” (沉香) in Chinese, it was first described in the Miscellaneous Records of Famous Physicians written in the Jin dynasty under different names such as Xun Lu Xiang (薰陆香) and Feng Xiang (枫香).[33] The character “Chen” means sink, whereas “Xiang” means fragrance or incense. The trunk has a strong fragrance, and it can be burnt as incense. Aquilariae Lignum Resinatum has many therapeutic functions, such as moving qi and relieving pain, directing the rebellious qi downward and stopping vomiting, and warming the kidneys to aid in qi absorption.[34] Aquilariae Lignum Resinatum is traditionally used to treat many ill conditions such as gastrointestinal disorders, asthma, and pain. A recent study on its phytochemistry and pharmacological effects revealed new bioactive compounds in Aquilariae Lignum Resinatum, and these compounds have various pharmacological effects such as anti-inflammatory, anti-tumor, anti-bacterial, and anti-fungal effects.[35] Although advances have been made in the discovery of new compounds and novel bioactivities, further studies are needed to evaluate their clinical efficacy. Dendrobium nobile Lindl (D. nobile), a well-known precious plant, is also known as noble Dendrobium, as well as Jin Chai Shi Hu (金钗石斛) in Chinese. It is one of the main Dendrobium species recorded in the Chinese Pharmacopoeia, and it has both ornamental and medicinal value.[3637] In China, the utilization of Dendrobium as a medicine and health food can be traced back to 1500 years ago. D. nobile has been used to treat diabetes, chronic atrophic gastritis, neurodegenerative diseases related to aging, and cardiovascular disease.[3839] Various phytochemical compounds have been identified in D. nobile, such as alkaloids, bibenzyl, phenanthrene, phenylpropanoids, and polysaccharides. Pharmacological studies illustrated that these active ingredients of D. nobile have multiple health-promoting effects, and many of the pharmacological effects have significant ethno-medicinal values, such as anti-tumor, anti-inflammatory, immunomodulatory, anti-fatigue, anti-aging, and hypoglycemic.[40] Future Perspectives With its long history of practical uses, TCM is gaining popularity, and materials have been marketed as dietary supplements or been developed into herbal drugs. Because of increasing demand for medicinal plants, pressure is mounting on existing resources, threatening the depletion of some species in their natural habitats. The situation has spurred researchers to develop innovative methods for the cultivation of herbal plants to meet the market needs and encourage ecological conservation. Therefore, the sustainability of rare and precious Chinese medicine resources and Chinese medicine in general relies on a well-balanced combination of wild collection, cultivation, and natural fostering. Funding None. Ethical approval This article does not contain any studies with human or animal subjects performed by either of the authors. Author contributions Hong-Xi Xu and Zhi-Xiu Lin wrote and reviewed the article. Conflict of interest None

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