Background

In recent years, as the use of Chinese medicinal materials (CMMs) has increased, the international attention paid to the safety, stability and efficacy of CMMs has increased. Some authentic and superior CMMs that are grown in specific regions and widely recognized as having better therapeutic effects are called daodi medicinal materials (DMMs) [1]. DMMs, based on the theory, origin, processing, and prominent curative effect of CMMs, are the essence of Chinese cultural heritage [45], Polygonum multiflorum Thunb. [46], Morinda officinalis How [47], Aquilaria sinensis (Lour.) Gilg [48], Rheum tanguticum Maxim. ex Balf. [49], Amomum villosum Lour. [50], etc.

Traditional descriptions of daodi medicinal materials by famous physicians in ancient China

In the use of CMMs, a large emphasis has been placed on the identification of DMMs since ancient times. As recorded in Shen Nong Ben Cao **g (The Divine Shennong’s Classic of Materia Medica, 25–220 A.D.) [51], “each medicinal material has laws for its production region, authenticity, and freshness.” In various chapters of that book, locations in ancient kingdoms and regions, such as mountain valley, river valley or marshes, were mentioned for the first time as medicinal herbs sources. This record indicates that different CMMs come from certain specific areas. In his immense book Ben Cao **g Ji Zhu (Collection of Commentaries on the Classic of the Materia Medica, 480–498 A.D.) [52], Tao Hong**g, a well-known physician in the Northern and Southern Dynasties (420–589 A.D.), used such terms “good”, “quite good”, “fairly good”, “excellent” and “best” to describe the effects of over 40 medicinal herbals commonly used in medical treatment. Moreover, correlations between the sources, developmental stages and efficacy of these medicinal herbs were described. Sun Simiao, a famous physician and pharmacologist of the Tang Dynasty (618–907 A.D.), stated the following in his book Qian ** Yi Fang (Formulas Worth a Thousand Gold Pieces, 682 A.D.) [53]: “Medicinal herbs used by ancient physicians were always from designated original sources, which accounted for their great effectiveness in medical treatment”. In that book, he comprehensively sorted 519 DMMs and systematically stipulated 133 regions of production. According to Kou Zongshi, a famous physician of the Song Dynasty (960–1279 A.D.), in his book Ben Cao Yan Yi (Extension of the Materia Medica, 1116 A.D.), “in prescribing medicinal herbs, care should always be taken to select those from proper sources to ensure their effectiveness”, greatly emphasizing the designated original sources of medicinal herbs [54]. During the ** and Yuan Dynasties (1115–1368 A.D.), the text Yong Yao Fa **ang (Medication Method, 1249 A.D.) also suggested that one could achieve excellent treatment results only by using DMMs with proper production regions and harvest time. Then, the Ming Dynasty (1368-1644 A.D.) document Ben Cao Meng Quan (Materia Medica Companion, 1565 A.D.) stated that “the effect will be definitely different if medicinal materials are produced in a different environment” [55]. The record in Yi Xue Yuan Liu Shi (Origins of Medicine, 1767 A.D.) attached similar importance to the use of DMMs collected from certain original sources [56]. All of this historical literature showed that the use of DMMs has been a practice since ancient times.

The scientific elucidation of daodi medicinal materials

DMMs are the subset of CMMs that meet the highest quality criteria. DMMs are not only associated with specific geographic regions (Fig. 4) but also linked to the chemical components and pharmacological function of CMMs.

Fig. 4
figure 4

The distribution of some daodi medicinal materials in China

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Chemical components

As we described above, ecological environments such as topography, sunshine, soil, and water directly influence the secondary metabolites (many of which are bioactive components) in medicinal herbs. The many names of DMMs reflect the connotations of production regions; for instance, “qin pi” (Fraxinus chinensis Roxb.), “fen qi” (Astragalus membranaceus (Fisch.) Bge.), “huai di huang” (Rehmannia glutinosa Libosch.) and “ba dou” (Croton tiglium L.), where “qin”, “fen”, “huai”, and “ba” refer to the names of regions used over the course of ancient Western Zhou Dynasty (1046–771 B.C.) [1]. Modern experimental research has validated that DMMs growing in a certain production region are often of high quality (Table 1). For example, the ancient Chinese medicine book **n **u Ben Cao (Newly Revised Materia Medica, 659 A.D.) [57] said that “Fraxinus chinensis Roxb., which can change the color of water to a fluorescent color after soaking, is thought to be superior in quality” (Fig. 5). Currently, scientific evidence supporting the rational for such description is available. F. chinensis produced from Shaanxi province has a higher content of aesculin and aesculetin than that produced in Sichuan province and Liaoning province, and its stronger fluorescence reaction is consistent with the description written in ancient times [58, 59]. The same observation is true for Astragalus membranaceus (Fisch.) Bge. This herb is principally cultivated in a region in Shanxi province, and the cultivar produced in this region contains more astragaloside than do cultivars produced in Shandong, Inner Mongolia, Hebei and Jilin provinces [60]. It is generally recognized that Rehmannia glutinosa Libosch. cultivated in Henan province is of particularly high quality. Modern experimental studies have demonstrated that higher levels of the active constituent catalpol content are present in R. glutinosa grown in this region than in cultivars grown in areas of **anyang (in Shaanxi province) and Dali (in Shaanxi province) [61]. Similarly, A. villosum cultivated in Yangchun (in Guangdong province) is believed to be superior in quality. The effective medicinal elements in A. villosum is bornyl acetate. Modern experimental research has validated that Yangchun-cultivated A. villosum has the highest effective component content among different populations [62,63,64]. In other example, P. cablin cultivated in Shipai (in Guangzhou city, Guangdong province) is of particularly high quality. It produced higher levels of the active constituent pogostone than that cultivated in Gaoyao (in Zhaoqing city, Guangdong province), Leizhou (in Zhanjiang city, Guangdong province), Wuchuan (in Zhanjiang city, Guangdong province) and Hainan province [65,66,67,68,69,70]. Interestingly, the same is true for toxicology. A. carmichaelii produced from plantation sites at Jiangyou county of Sichuan province is believed to be superior in quality. The proportions of the major bioactive constituents monoester alkaloids to toxic constituents diester alkaloids amount among 5 samples of A. carmichaelii from different localities were well correlative with their regions of cultivation. The highest proportion occurred in cultivar Jiangyou (in Sichuan province), followed by cultivars Hanzhong (in Shaaxi province), Butuo (in Sichuan province), Weishan (in Yunnan province), and Anxian (in Sichuan province) [71].

Table 1 The contents (%) of active constituents in different Chinese medicinal materials in daodi production region and non-daodi production regions
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Fig. 5
figure 5

The herbal classic **n **u Ben Cao (Newly Revised Materia Medica) describes the metachromatism-based quality evaluation of “qin pi” (Fraxinus chinensis Roxb.)

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Pharmacological functions

Pharmacological functions are actually the outside manifestations of CMMs. In the case of DMMs, the conditions in a certain region are thought to confer clinical superiority, and for this reason, DMMs are considered the most efficacious among CMMs [72]. Scientific evidence supporting the alleged clinical superiority of DMMs is the subject of ongoing research. For example, Dendrobium huoshanense C. Z. Tang et S. J. Cheng produced in Huoshan (in Anhui province) is considered to be superior in quality. Accordingly, the hepatoprotective effect is the best for the Huoshan cultivar, second for the Yunnan cultivar, and last for the other region cultivars [73]. P. cablin has been classified into two chemotypes, the patchoulol-type, including cultivars HN and ZJ, and the pogostone-type, including cultivars SP and GY. Accordingly, this cultivars produced in GY are more potent than those from ZJ in terms of promoting digestion [74] and antibacterial [75] effects. In addition, the toxicity of DMMs is often less potent than that of non-DMMs. For instance, P. multiflorum is principally cultivated in region Deqing county of Guangdong province, which has the largest output and the longest history of medicinal use. Accordingly, cultivar Deqing showed less potent cytotoxicity than cultivar Chongqing in HepG2 and LO2 cells [76]. These studies show considerable promise for explaining the scientific mechanism of DMM superiority.

Daodi medicinal materials are the basis of the medicinal industry and clinical practice

CMMs are the materials processed into decoction ingredients or used to produce proprietary drugs. The identification of DMMs is important in quality evaluation and disease treatment. In addition to the optimum harvest season, the processing and standard prescription of CMMs produce the unique characteristics of DMMs, and a plausible production chain of CMMs is hypothesized in Fig. 6. The production chain of CMMs is based on the content we described above, including populations, designated growing regions (daodi), and harvest season, as well as the extensive quality control knowledge accumulated for CMMs by Liu et al. [77,78,79,80]. Compared to previous production chain of CMMs [77,78,79,80], factors such as populations, designated growing regions and harvest time directly influenced the quality of CMMs were emphasized. Every procedure in the production chain should be standardized to guarantee the prominent curative effect of medicinal materials. For example, the manufacturing procedure for Pinellia ternata (Thunb.) Breit. was standardized by orthogonal design [81]. In addition, modern analytical methods have revealed the processing mechanism of many CMMs, including Coptis chinensis Franch. [82,83,84], Xanthium sibiricum Patr. [85,86,87], Siegesbeckia orientalis L. [88, 89], Descurainia sophia (L.) Webb. ex Prantl. [90, 91], Cassia obtusifolia L. [92, 93], etc. Additionally, cooperation among universities, research institutes and pharmaceutical manufacturers should be strengthened to communicate information regarding CMMs.

Fig. 6
figure 6

A putative production chain for CMMs

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Conclusions

DMMs have long maintained, currently have, and will continue to maintain a good reputation on the basis of their excellent curative effects. In our review, DMM is the specific term for pure, superior medicinal herbs with the following characteristics: optimum harvest season (reflecting the appropriate developmental stage of the plant), scrupulous processing, traditional preparation technology, etc. Historical literature, modern phytochemical and pharmacological methods have provided additional scientific data and a theoretical basis to validate the mechanisms of DMMs. In addition, every procedure in the production chain of CMMs should be standardized to guarantee the prominent curative effect of medicinal materials. Effectively establishing a correlation among the active components, clinical efficacy and identity of DMMs is an important aspect in the quality evaluation of CMMs. The core scientific elucidation of DMMs should be continuously carried out, and multidisciplinary measures should be adopted to explore scientific and practical methodologies for the further research of DMMs.