“ The phenomenon of “same origin, different efficacy” refers to the situation in which medicinal materials derived from the same medicinal plant yield different prepared slices due to variations in the part used, stage of maturity, processing methods, and other factors. Ancient Chinese medical texts have long documented this phenomenon of “same origin, different efficacy” in the use of herbal medicines and the traditional practice of “drawing analogies based on symbolic correspondences” in pharmacopoeia formulation, while preserving extensive information on the botanical origins, properties, and therapeutic effects of such herbs. This has provided crucial clues for subsequent research on the verification and interpretation of materia medica. In recent years, as studies on the “same origin, different efficacy” phenomenon have deepened, related publications have steadily increased, with scholars primarily employing textual analysis of classical materia medica and investigations into the material basis of these herbs to elucidate their mechanisms of action. However, these mechanisms have yet to be systematically clarified within the framework of current pharmacological theory, and their underlying principles still require integrated research and synthesis that bridge macroscopic TCM theoretical foundations with microscopic mechanistic insights. Our research group has consistently sought to apply supramolecular chemistry to the study of TCM theory and has achieved breakthrough progress in this area. ^[1-5] It has been found that the “homologous but different efficacy” mechanism can be preliminarily explained by supramolecular chemistry theory: both traditional Chinese medicines and the human body are biological mega-supramolecular systems formed through supramolecular self-recognition, self-organization, self-assembly, and self-replication. When components of traditional Chinese medicines enter the body as guests, the “molecular imprinting template” complexes within the medicine interact with “target sites” that possess similar spatial cavities and channels under the influence of “gas-extraction interactions.” The underlying mechanism of action conforms to the autonomous operational principles of supramolecular “molecular imprinting templates,” such that identical (or similar) sets of “imprinting templates” exert identical (or similar) pharmacological effects on the meridians and viscera—and vice versa. Based on the characteristics of in vivo supramolecular “imprinting templates,” when “homologous” constituents enter the body, the degree of similarity or dissimilarity between their in vivo molecular “imprinting templates” and those of the host determines whether they produce “homologous” or “heterologous” effects after metabolism. This paper provides a comprehensive review of the historical evolution, materia medica verification, and research progress on the patterns of medication associated with the “homologous but different efficacy” phenomenon in traditional Chinese medicine, while elucidating its supramolecular mechanisms. Such an analysis is of significant economic and social value for advancing in-depth research on this phenomenon, enhancing quality control standards, and promoting industrialization.

1   “ Same origin, different effects ” Historical Evolution of Traditional Chinese Medicine Usage

The phenomenon of “same origin, different effects” in the use of traditional Chinese medicines was already documented as early as the Qin and Han dynasties, as recorded in the “Biographies of Famous Physicians,” a compendium compiled by physicians of successive generations during those periods. ^[6] The CPC Lists “Same Origin, Different Effects” Traditional Chinese Medicines 27 Species such as the root, leaves, and fruits of Alisma; the root and leaves of Polygala; the fruits, leaves, and stems of Vitex; Aconitum carmichaelii, Aconitum kusnezoffii, Aconitum ferox, and Aconitum laterale; Typha pollen and cattail; Chinese juniper wood, fruits, leaves, and inner bark; jujube fruit and leaves; pine knots, needles, cones, resin, and white bark from the roots; peach fruit and peach kernels. Their respective therapeutic effects are also listed, for example: “The root of Alisma is primarily indicated for deficiency and exhaustion, as well as the Five Debilities… The leaves (of Alisma) are mainly used to treat severe wind-related conditions and insufficient lactation… The fruits (of Alisma) are indicated for wind-stasis arthralgia and polydipsia.”

During the Sui and Tang dynasties, the economy and culture flourished, and significant achievements were made in the field of medicine, such as the Tang dynasty’s “Newly Revised Materia Medica.” ^[7] middle A total of “homologous but different-effect” traditional Chinese medicines are listed. 100 In addition, the text further expands the category of “medicinal herbs with the same origin but different effects,” such as soapberry and soapnut, elm bark and elm leaves, coix seed and coix root, peach flesh, peach kernel, peach gum, peach hairs, peach skin, and peach gall; neem fruit and neem root; trichosanthes fruit and trichosanthes root; sophora fruit and sophora branches; hound’s-tongue and tianmingjing; citrus peel and pomelo peel; pomegranate root and pomegranate bark; buckthorn and buckthorn bark; sour jujube and sour jujube seed; curcuma and turmeric; white lotus and lotus rhizome; willow cinnamon and cassia bark; maple bark and fragrant resin; winter melon and winter melon seeds; plum root and plum kernel; water smartweed and smartweed fruit; papaya and papaya seed; evodia and evodia root; five-leafed aralia and five-leafed aralia bark, among others. During the Tang dynasty, officials adhered to the principle that “Although the ‘Shennong’s Classic of Materia Medica’ may be incomplete, any remedy with proven efficacy must be recorded; although the ‘Supplementary Records’ may still exist, any claim lacking empirical support must be corrected. By comparing similarities and differences and carefully selecting what to retain or discard,” conducting on-site investigations into the origins and varieties of medicinal materials, thereby clarifying previous errors in the nomenclature and botanical origins of drugs as documented in earlier materia medica works and providing some guidance for the rational use of “medicinal herbs with the same origin but different effects.” The work also includes a greater number of foreign medicinal substances widely used in folk practice, some of which likewise fall under the category of “medicinal herbs with the same origin but different effects,” such as curcuma and turmeric, as well as pomegranate root and pomegranate bark.

During the Song, Jin, and Yuan dynasties, rapid developments in the economy, culture, and science and technology—particularly the widespread adoption of movable-type printing—further advanced the theoretical framework of “same origin, different effects” in the use of traditional Chinese medicines. On the one hand, during the Song dynasty, Tang Shenwei compiled and authored the “Compendium of Materia Medica Verified by Classics and Histories.” ^[8] Based on the “Tang Ben Cao,” additional “homologous but differently effective” traditional Chinese medicines were added, with a total of such medicines listed. 200 Other varieties include toon seed pods and toon leaves, fishing camphor root and fishing camphor bark, ear fruit and ear fruit leaves, thorny spines and thorny spines flowers, plum fruits and plum kernels, magnolia flowers and magnolia bark, sour jujubes and sour jujube seeds, citron peel and citron fruit, cornelian cherry roots and cornelian cherry bark, catalpa white bark and catalpa leaves, and so on. On the other hand, during this period, medical scholars began to discuss the phenomenon of “same origin, different effects” in the use of Chinese medicinal herbs, as well as the principles governing their clinical application; for example, Li Dongyuan, one of the Four Great Masters of the Jin–Yuan period, in his “Supplementary Treatise on the Properties of Medicinal Herbs in the Pearl Chamber,” ^[9] As stated: “The root (Dang Gui) stops bleeding and ascends; the body (Dang Gui) nourishes the blood and remains in the middle.” “The root of Dang Gui is used to arrest and direct the blood downward, while the whole plant of Dang Gui is employed to invigorate the blood without causing it to disperse”; in his work “Yong Yao Fa Xiang,” he states: “All medicinal roots are classified as upper, middle, and lower. For conditions affecting the upper half of the body, the head of the herb is used; for the middle region, the body; and for the lower half, the tip. Thus, herbs are divided into upper, middle, and lower based on their head, body, and tip—this classification is grounded in analogy and resemblance.”

During the Ming and Qing dynasties, research on the TCM pharmacological theory of “shared origin, different effects” reached a peak. In the Ming dynasty, Li Shizhen authored the Compendium of Materia Medica. ^[10] A total of “homologous but different-effect” traditional Chinese medicines are listed. 300 He examined numerous other species, such as ferns and fern roots, quinoa and quinoa stems, taro corms, taro stems and leaves, and taro petioles; lily roots, lily flowers, and lily seeds; mountain peony roots, mountain peony flowers, and mountain peony stamens; daylily seedlings and flowers, and daylily roots; cucumber fruits, cucumber leaves, and cucumber roots; coix seeds, coix roots, and coix leaves, among others. In addition, he meticulously investigated the botanical origins, nomenclature, geographic origins, processing methods of each medicinal material, and systematically categorized “same origin, different effects” Chinese herbs based on their distinct parts. He also expounded on the principles governing the clinical application of such herbs, stating: “Within a single substance, the root ascends while the tip descends; raw materials ascend, whereas processed ones descend—this principle of ascending and descending applies both to the herb itself and to the human body… In general, for roots that grow underground, those extending more than half their length above ground will ascend, while those remaining below half their length will descend. Although it is the same herb, its root and tip exhibit distinct properties; if used improperly, the therapeutic effect may be lost, and the medicine may prove entirely ineffective.” Other scholars have likewise discussed “same origin, different effects” in their respective works. Regularity in medication, as exemplified by Cheng Xingxuan of the Qing dynasty in his “Yi Shu.” ^[11] It is stated: “When the natures are identical, they correspond accordingly: for example, the head of a medicinal substance corresponds to the head; the stem corresponds to the limbs; and the bark corresponds to the bark.” During the Qing dynasty, Chen Shiduo wrote in his work “New Compilation of Materia Medica”… ^[12] “It is often asked: ‘Ephedra promotes sweating, yet the root and nodes of ephedra arrest it—why is this so? It is one and the same herb, yet it is employed in two distinct therapeutic ways.’” — Wu Yiluo of the Qing dynasty, in his Compendium of Materia Medica, Revised and Updated. ^[13] It summarizes the relationship between “homologous yet different effects” in traditional Chinese medicine and the properties and therapeutic actions of herbs: “Herbs that act on the limbs do so through the branches; those that act on the skin do so through the皮; those that act on the heart or the trunk penetrate internally to reach the zang-fu organs. Herbs with a light, airy nature ascend to the heart and lungs; those with a heavy, dense nature descend to the liver and kidneys. Hollow herbs disperse the exterior; solid herbs attack the interior. Dry, desiccating herbs enter the qi level; moist, nourishing herbs enter the blood level. Thus, whether ascending or descending, internal or external, each follows its own kind.”

In modern times, with the rapid development of disciplines such as Chinese medicinal chemistry, pharmaceutical analysis, and pharmacology, scholars have intensified their efforts to develop “homologous but different in efficacy” traditional Chinese medicines, and the number of such preparations continues to grow. The author has examined works such as the Compendium of Chinese Herbal Medicines Nationwide, the Great Dictionary of Traditional Chinese Medicine, and the Chinese Materia Medica. ^[14-16] Statistical analysis in reference works reveals a total of “homologous but different-effect” traditional Chinese medicines. 800 Other species. The same botanical origin only 1 Those with a single medicinal part are called single-part varieties, while those with 2 Species with two or more medicinal parts are referred to as multi-part varieties; the single-part entries for Chinese medicinal materials listed in successive editions of the Chinese Pharmacopoeia The number of single-site and multiple-site cases has generally shown a steady increasing trend, with the number of multiple-site cases specified in the Chinese Pharmacopoeia. 2015 Reached the annual edition 83 kind ^[17] 。 In addition, when scholars have examined the patterns of change in the same botanical origin across multiple parts in successive editions of the Chinese Pharmacopoeia, they have summarized the factors underlying these changes as follows: 2 Points where the toxic effects differ, or where changes in the parts used have occurred due to the comprehensive utilization of Chinese medicinal material resources or the endangered status of wild resources, such as in the *Chinese Pharmacopoeia*. 1985 The annual edition stipulates that Asarum is entirely The herb is used in traditional medicine; however, subsequent research has shown that the stems and leaves of Asarum contain aristolochic acid, a toxic compound, whereas the roots and rhizomes do not. Therefore, the Chinese Pharmacopoeia 2005 The 20XX edition stipulates that the medicinal parts of Asarum are the roots and rhizomes. ^[17-18] ， Furthermore, changes in the parts used for medicinal purposes may occur due to the comprehensive development and utilization of Chinese medicinal resources or the endangerment of wild resources; the Chinese Pharmacopoeia 1995 The current edition adds the leaf of Panax ginseng as a new medicinal part, as stipulated in the Chinese Pharmacopoeia. 2005 The current edition adds hawthorn leaf as a new medicinal part for hawthorn, eucommia leaf as a new medicinal part for eucommia, and schizonepeta spike as a new medicinal part for schizonepeta. The Chinese Pharmacopoeia 2010 The latest edition adds peach branches as a new medicinal part of the peach, according to the Chinese Pharmacopoeia. 2015 The latest edition adds new medicinal parts of Poria, such as the periderm of Poria, among others.

In summary, the original meaning of the “same origin, different effects” phenomenon in traditional Chinese medicine stems from the observation that harvesting different parts of a medicinal herb at different times of the year yields varying therapeutic outcomes. This phenomenon was systematically generalized through “analogy and classification” based on the clinical efficacy of various herbal parts, rooted in centuries of clinical practice in TCM. Ancient practitioners attributed to this principle the function of “analogy and classification,” thereby embodying the distinctive dialectical thinking characteristic of TCM. From a TCM perspective, the “same origin, different effects” phenomenon is not merely a matter of “roots, stems, leaves, flowers, fruits, and seeds” conforming to their respective categories; it also reflects the principle that “the head of a drug corresponds to the head, the stem to the limbs, and the bark to the bark,” indicating that similar substances share common underlying qualities. Early scholars first identified this universal principle for guiding herbal prescription, then proceeded to analyze and compare the distinct pharmacological effects of different parts of each individual herb, ultimately grounding their conclusions in clinical efficacy. However, due to the limited scientific and technological resources available to ancient practitioners, their understanding of the “same origin, different effects” phenomenon remained constrained: they relied primarily on subjective, macroscopic observations of how herbs acted upon the human body, often neglecting more refined, microscopic rational analysis and lacking objective experimental methods and evaluation metrics. Accordingly, this paper seeks to elucidate the microchemical mechanisms underlying the “same origin, different effects” phenomenon by applying supramolecular chemistry theory, investigating the interaction between groups of herbal constituents and the “imprint templates” of the meridians and zang-fu organs, and thereby advancing the modernization of TCM theory.

2 “ Same origin, different effects ” Current Research Status on the Use of Traditional Chinese Medicines

2.1   The textual research on materia medica is “ Same origin, different effects ” An important basis for the use of traditional Chinese medicine

      1963 Xie Zongwan, a renowned herbalist of the year ^[19] It is proposed that the objective of materia medica verification is to examine, from the perspective of botanical identity, the medicinal substances recorded in pharmacopeias of successive dynasties, with the aim of identifying the authentic, genuine preparations used by ancient practitioners. At present, materia medica verification is defined as a research approach grounded in historical pharmacopeial literature, involving the analysis, comparison, and critical appraisal of the names, origins, morphological characteristics, olfactory and gustatory attributes, and therapeutic properties of drugs as documented across the ages, thereby clarifying the historical usage of complex taxonomic categories such as superior, inferior, and adulterated products. ^[20] 。

The development of “homologous but different in efficacy” traditional Chinese medicines involves identifying, within a particular herbal materia medica, variations arising from factors such as maturity level, processing methods, and the specific plant part used in medicinal preparation. Traditional Chinese medicines with the same therapeutic effects. For “homologous but different in efficacy” TCMs, from their discovery and promotion to gaining recognition from physicians and patients, the first step is to conduct a meticulous textual study of the materia medica: ( 1 ) Exam To verify “same origin, different efficacy,” it is necessary to examine the botanical origin, name, place of production, and processing methods of the traditional Chinese medicine in order to determine whether the condition of “same origin” is met, thereby assessing “same origin, different efficacy.” Conduct in-depth exploration of the “common origin” relationships among traditional Chinese medicines. 2 ) Exam To verify the “same origin, different efficacy” of traditional Chinese medicines, this study examines the differences in their physical characteristics, odor, medicinal properties, and primary indications and therapeutic functions, and compares the extent of “different efficacy,” thereby providing support for research into their material basis.

Whether a traditional Chinese medicine qualifies as “same origin, different efficacy” can be determined by assessing whether its botanical origin and processing methods meet the criteria of “same origin” and “different efficacy.” If it fails to satisfy either the “same origin” or the “different efficacy” criterion, it is not considered a “same origin, different efficacy” TCM. ” Traditional Chinese medicine. When examining the botanical origins, although names such as “Zizhu Ye” (Purple Pearl Leaf) and “Guangdong Zizhu,” “Daye Zizhu,” and “Luhua Zizhu” may suggest that they are “same source, different effects,” their botanical origins are actually distinct: Zizhu Ye refers to the dried leaves of Duranta erecta, a plant in the Verbenaceae family, whereas Guangdong Zizhu, Daye Zizhu, and Luhua Zizhu respectively refer to the dried stems, branches, and leaves of Guangdong Zizhu, Daye Zizhu, and Luhua Zizhu, all plants in the Verbenaceae family. ^[21] Therefore, it does not fall under the category of “traditional Chinese medicines with the same origin but different effects”; furthermore, according to research by some scholars, bee nests are constructed by insects of the Vespidae family, such as the giant hornet, the Japanese long-legged hornet, or the heteromorphic hornet. ^[22] Moreover, its botanical origin differs from that of propolis (from the Italian honeybee), beeswax (from the Chinese honeybee or the Italian honeybee), and honey (from the Chinese honeybee or the Italian honeybee); therefore, it cannot be classified as a “same-source, different-effect” traditional Chinese medicine. In addition, a traditional Chinese medicinal material and its synthetically produced substitute also do not fall under the category of “same-source, different-effect” medicines; for example, artificial bezoar (synthetically produced) and natural bezoar (the dried gallstone derived from bovine animals) are not considered “same-source, different-effect” medicines because their botanical origins are distinct. ^[23-24] However, crude herbal medicines obtained solely through simple processing methods do not qualify as “same origin, different efficacy” herbs. For example, tortoise shell and tortoise-shell glue are not considered “same origin, different efficacy” herbs, because tortoise-shell glue is merely a solid adhesive prepared by decocting and concentrating tortoise shell in water, without the addition of any excipients; essentially, it is simply a refined product that does not alter the herb’s intrinsic properties or therapeutic effects. ^[25] For example, talc, talcum powder, deer antler and deer antler glue, and deer antler frost all fall into this category; therefore, they are not considered “homologous but with different efficacies” traditional Chinese medicines. In addition, many TCMs listed in the Chinese Pharmacopoeia originate from multiple plant parts, and thus are also not classified as “homologous but with different efficacies” TCMs—for instance, catechu (peeled branches and stems), evodia (leaves and young twigs with leaves), notoginseng (roots and rhizomes), cortex of dictamni (root bark or near-root bark), and senecio (above-ground parts)—all of which are regarded as having no discernible differences in therapeutic efficacy. Although the primary root, the cut end (rhizome), and the lateral roots of notoginseng can be distinguished as distinct parts through pattern recognition, their high-performance liquid chromatographic profiles high performance liquid chromatography ， High-Performance Liquid Chromatography ) The fingerprint profiles exhibit a very high degree of similarity ( 0.994 ~ 1.000 ), making it difficult to reflect 3 Differences among parties ^[26] 。

Therefore, pharmacopoeial verification serves as a crucial basis for identifying “same origin, different efficacy” traditional Chinese medicines. Through such verification, the historical usage of these varieties can be clarified, thereby providing support for their further development.

2.2   “ Same origin, different effects ” Classification of Traditional Chinese Medicines and Principles of Prescription

“Same origin, different effects” traditional Chinese medicines mainly include 3 Three scenarios: Chinese medicinal materials from different parts with different therapeutic effects; the same part of a Chinese medicinal material at different stages of maturity, each with distinct therapeutic effects; and the same part of a Chinese medicinal material before and after processing, each exhibiting different therapeutic effects. Pharmacopoeia of the People’s Republic of China 2020 Year edition ^[27] List of commonly used traditional Chinese medicines 614 species, collectively referred to as “homologous but different in efficacy” traditional Chinese medicines 128 Species ( 53 Group “homologous but different effects” traditional Chinese medicines), accounting for 20.85% , among which there are Chinese medicinal herbs with different parts and different effects. 37 For example, there are Chinese medicinal herbs from the same part of the body that differ in their degree of maturity and therapeutic effects. 5 Example: Traditional Chinese medicines that exhibit different therapeutic effects before and after processing on the same part of the body include: 19 For example, “homologous but different in efficacy” traditional Chinese medicines mainly consist of herbs from different parts of the same plant that exhibit distinct therapeutic effects.

“Same origin, different effects” refers to traditional Chinese medicines that share similar chemical compositions yet possess distinct characteristics, resulting in overlapping functional similarities while also exhibiting unique properties. The degree of “different effects” among such medicines varies, and can broadly be categorized as follows: 2 class, 1 “Homologous yet different in efficacy” refers to traditional Chinese medicines with similar therapeutic effects, meaning the degree of their “differential efficacy” is relatively small. For example, ginseng and ginseng leaves both belong to the category of qi-tonifying herbs and can both tonify qi, benefit the lungs, and generate body fluids. ^[28] ; Eucommia bark and Eucommia leaves both belong to the category of yang-tonifying herbs and can both tonify the liver and kidneys and strengthen the tendons and bones. ^[29] ; Hawthorn and hawthorn leaves both belong to the category of herbs that regulate qi and disperse blood stasis, and they both can regulate qi, disperse blood stasis, transform turbid substances, and modulate lipids. ^[30] ; Albizzia bark and Albizzia flowers both belong to the category of herbs that nourish the heart and calm the spirit, and both can relieve depression and tranquilize the mind. ^[31] Furthermore, the aforementioned herbs all belong to different body parts and exhibit distinct therapeutic effects. For example, Zhike, Zhi Shi, Qingpi, and Chenpi are all classified as qi-regulating herbs; they share the same botanical origin but differ in their stage of maturity and corresponding clinical actions. Similarly, Gancao and Zhi Gancao, Hongqi and Zhi Hongqi, as well as Huangqi and Zhi Huangqi, are all categorized as qi-tonifying herbs; they originate from the same part of the plant but differ in their processing methods—before and after stir-frying—and consequently in their therapeutic properties. 2 This refers to the phenomenon of “homologous but different effects” in traditional Chinese medicine, where the degree of “different efficacy” is substantial. For example, Ephedra and Ephedra Root: Ephedra is a pungent-warm exterior-releasing herb that promotes sweating to dispel cold, whereas Ephedra Root is an astringent herb that consolidates the exterior and stops perspiration, used for spontaneous sweating and night sweats. ^[32] ; for example, goji berries, earth Gupi and goji berries are blood-tonifying herbs that nourish the liver and kidneys, enrich essence, and improve vision; in contrast, digupi is a herb that clears deficient heat, cooling the blood to eliminate internal heat and clearing the lungs to reduce fire. ^[33] ， All of the above are Chinese medicinal herbs that differ in both their part of the plant used and their therapeutic effects. For example, Rehmannia root and prepared Rehmannia root: Rehmannia root is a heat-clearing and blood-cooling herb, whereas prepared Rehmannia root is a blood-tonifying herb that nourishes the blood, enriches yin, benefits essence, and fills the marrow. Another example is Dryopteris crassirhizoma and charred Dryopteris crassirhizoma: Dryopteris crassirhizoma is a heat-clearing and detoxifying herb with anthelmintic properties, while charred Dryopteris crassirhizoma is a blood-cooling and hemostatic herb that can astringe and stop bleeding. All of these examples involve the same herbal material processed before and after preparation, yet exhibiting different therapeutic effects.

Through the Ancient and Modern Medical Case Cloud Platform ^[34-35] The frequency of each herb’s inclusion in prescriptions, as well as its distribution across ancient medical case records, modern medical case records, and case records of renowned physicians, was retrieved; the results are presented in the table. 1 Among the formulas of renowned physicians, herbs such as hawthorn leaves, eucommia leaves, aconite leaves, beeswax, propolis, liquidambar resin, and red astragalus have never been used. In modern medical case records, the number of Chinese medicinal herbs whose frequency of use in “homologous yet different effects” prescriptions exceeds that in ancient medical case records is 84 species, among which there are drugs that were not used in ancient medical records. 13 species; in ancient medical case records, the number of Chinese medicinal herbs with “same origin, different effects” that appear more frequently than those in modern medical case records is 32 species, among which those not used in modern medical case records are 4 species; by comparing this 2 Under these circumstances, it can be inferred that, with substantial advances in pharmacological and toxicological research, the frequency of use of most “homologous but different-effect” traditional Chinese medicines in modern clinical prescriptions has increased.

Scholars generally hold the view that, in the case of “homologous yet different effects” among various parts of a single herbal medicine, lighter-textured parts such as flowers, leaves, twigs, and bark are predominantly ascending-and-floating herbs. Examples include chrysanthemum flowers, senna leaves, cinnamon twig, and eucommia bark. These herbs are typically warm or hot in nature, with pungent and sweet flavors, and exert effects such as uplifting yang and dispersing exterior pathogenic factors, expelling wind and dispelling cold, and opening orifices. They are commonly employed in the treatment and prevention of conditions localized in the upper body or on the surface, or of disorders characterized by downward collapse of vital energy. The ascending-and-floating properties of flowers, leaves, twigs, and bark often arise from their content of aromatic volatile oils, such as protocatechuic acid, coumarin, cinnamic acid, cinnamaldehyde, and cinnamyl alcohol, 2- Methoxycinnamic acid and 2- Methoxy cinnamaldehyde can serve as a quality marker for Guizhi, while cinnamaldehyde can serve as a quality marker for Cinnamon. ^[36-37] Meanwhile, heavy-textured herbs such as seeds, fruits, and roots (or rhizomes) are mostly sinking herbs, including Gualouzi, ShanZha, and Dahuang; they generally have a cold or cool nature and a sour taste. Bitter, salty, and astringent flavors are typically employed to counteract pathological conditions that tend to descend or reside internally, often exerting effects such as purgation, heat clearance, reversal of upward-moving pathogenic factors, and astringency. Seeds, fruits, and roots (or rhizomes) frequently exhibit sedimentary properties due to their content of alkaloids, terpenes, steroids, flavonoids, and polysaccharides; for example, the main active constituents of Trichosanthes peel include flavonoids and amino acids, while Trichosanthes seeds are rich in terpenes and sterols, and Hedyotis root primarily contains proteins, terpenes, and polysaccharides. ^[38] , these constituents have a greater molecular weight than the volatile oil components, resulting in sedimentation. Studies have also demonstrated that, for traditional Chinese medicines with “homologous origin but different effects,” the active ingredient groups and mechanisms of action vary significantly across different parts used in medicinal preparations, as reported by Li Delong et al. ^[39] Based on network pharmacology - Molecular docking studies on the active ingredient clusters and mechanisms of action of different medicinal parts of mulberry in the prevention and treatment of diabetes have shown that the various medicinal parts of mulberry primarily: 11 Individual differential active ingredients and mitogen-activated protein kinases 8、 alpha- Serine / Threonine - Protein kinases, vascular endothelial growth factor A , Interleukin -6 , Peroxisome Proliferator-Activated Receptor gamma Wait 32 There is a core target, and the types of bioactive compounds and their respective molecular targets vary significantly depending on which part of the plant is used for medicinal purposes in the prevention and treatment of diabetes. In particular, mulberry fruits and mulberry branches appear to exert markedly different mechanisms of action in this context, which is consistent with the distinct properties, flavors, and meridian tropism of each plant part.

Moreover, the degree of maturity also influences the properties and therapeutic effects of “homologous but heteroactive” traditional Chinese medicines. As medicinal animals and plants mature, the types and amounts of metabolic products they produce vary, thereby giving rise to “heteroactivity.” For example, Citri Fructus Immaturus and Citri Pericarpium. 2 A commonly used qi-regulating herb is differentiated based on its degree of maturity; Zhi Shi is 5 ~ 6 The fruit falls naturally in autumn; the bitter orange is 7 Immature fruits with green peels. As the harvest period extends, the contents of various chemical constituents in lime fruits exhibit a declining trend. ^[40] For example, green tangerine peel and aged tangerine peel are derived from the pericarp of young or immature fruits, respectively; studies have shown that their contents of active constituents differ, as do their in vivo drug metabolism profiles. ^[41-42] 。

After processing, the “rising, descending, floating, and sinking” properties of medicinal materials can change: stir-frying with wine promotes rising, stir-frying with ginger disperses, stir-frying with vinegar astringes, and stir-frying with salt directs downward. For example, with licorice and honey-processed licorice (prepared by honey-frying), “it is not suitable for cases of fullness; if fullness is present, honey-processed licorice should be used to tonify, whereas if there is fullness, raw licorice should be used to purge.” Some scholars have analyzed the compositional changes in licorice before and after processing, finding that both the crude drug and its processed form, honey-processed licorice, exhibit alterations in chemical constituents. Alcohol-soluble extracts and glycyrrhizin can serve as key quality evaluation indicators for assessing the quality of honey-processed licorice before and after processing, while glycyrrhizic acid… G2 Glycyrrhizic acid, liquiritin, glycyrrhizin, isoliquiritin, glycyrrhizic acid glucoside, and isoliquiritigenin can serve as potential quality markers for licorice. ^[43-44] 。

On the surface, the phenomenon of “same origin, different effects” in traditional Chinese medicine appears to arise from variations in plant parts, maturity levels, processing methods, and other factors. In reality, however, such herbs share similar properties and therapeutic actions while also possessing distinct characteristics, which account for their overlapping pharmacological profiles—modern pharmacological studies have indeed demonstrated that some of their functions and mechanisms of action are comparable—yet their primary indications and clinical applications often exhibit unique features. Although scholars have conducted extensive research on the material basis of “same origin, different effects” herbs, a systematic theoretical framework has yet to be established. This gap reflects an oversight in integrating micro-level mechanisms with macro-level theories of traditional Chinese medicine. The underlying principles governing the clinical use of these herbs can be elucidated by the self-organizing regulatory patterns of supramolecular “molecular imprinting templates.”

3   “ Same origin, different effects ” The principles governing the use of traditional Chinese medicine can be elucidated by supramolecular chemistry. “ Imprint Template ” Interpretation of the Law of Autonomous Action

3.1   Supramolecular Chemistry Theory

French scientist Lehn ^[45] To begin, supramolecular chemistry, which arises from the interdisciplinary integration of chemistry, biology, informatics, life sciences, and other fields, is a type of host–guest chemistry in which ligands serve as the hosts and complexes act as the guests; it is also referred to as apparent chemistry. Molecular chemistry focuses on molecules as its objects of study, examining how atoms are linked by chemical bonds to form molecular entities; in contrast, supramolecular chemistry investigates intermolecular interactions by taking multiple molecules as its subject, with such interactions mediated by weak, noncovalent intermolecular forces. Supramolecular compounds are complex, highly organized chemical systems that arise from noncovalent interactions between a host molecule and one or more guest molecules. ^[46-47] 。

3.2  Main Characteristics of Supramolecular Structures and Their Functions ^[1-5,48-50]

Supramolecules are hosts and guests. 2 Some non-bonded compounds are composed of discrete molecular units, with the degree of their association determined by conformation; the host molecule possesses a well-defined cavity that can accommodate small molecules whose shape is identical or similar to the cavity’s template, thereby establishing a lock-and-key relationship. The host molecule may cyclize to form a closed cavity, or it may undergo non-cyclic polymerization to generate an open cavity, adopting various architectures such as helical structures, sheets, micelles, nanocapsules, organelles, and even whole cells, thus giving rise to diverse supramolecular assemblies ranging from small to large molecules. Cells themselves constitute vast supramolecular assembly systems, while the human body represents an even more complex, hierarchical supramolecular system, encompassing channel-like structures and imprint templates that span the spectrum from single molecules to various supramolecular aggregates. Supramolecular host–guest complexes, linked through specific cavity templates at different levels, organize into meridians and viscera, as well as tissues and organs, enabling interactions with guest molecules that match the corresponding template. Once the host and guest components of a supramolecular assembly combine, the resulting supramolecule undergoes alterations in the properties of both the host and guest molecules; on a macroscopic scale, this manifests as the migration of guest molecules within the host matrix and the emergence of anisotropic physicochemical properties, while the host molecule’s own physicochemical characteristics also change.

3.3   “ Same origin, different effects ” Supramolecules in Traditional Chinese Medicine “ Imprint Template ” The Interpretation of Theory

From a supramolecular perspective, biomolecules in the human body—such as amino acids, purines, and pyrimidines—as well as macromolecules like polypeptides and polynucleotides—self-organize, self-assemble, undergo self-recognition, and replicate to form supramolecular structures with specific functions. Various small biomolecules serve as template molecules, while amino acids, monosaccharides, and nucleotides act as functional monomers for the synthesis of molecularly imprinted polymers. Examples include enzymatic catalysis in diverse biochemical metabolic reactions, protein synthesis based on amino acids, and glycogen synthesis in the liver driven by glucose. ^[48] These synthetic supramolecular hosts further assemble into large, functional supramolecular assemblies through subunit integration, which then organize into organelles, subsequently giving rise to cells. These cells, through self-replication and differentiation, generate various specialized cell types that interconnect to form tissues and organs, ultimately constituting the entire human body. In this multilevel process of supramolecular assembly, the parent supramolecular structure retains the “imprint template” of its daughter supramolecular structures; thus, the human body is a giant, highly complex supramolecular entity—a “giant imprinted polymer”—formed by the hierarchical arrangement of diverse “imprint templates” linked together according to a specific spatial architecture of cavities and channels. ^[48-50] 。

Supramolecular “imprinting templates” are template molecules that exhibit complete spatial structural and binding-site complementarity; essentially, they are 2 The interaction processes involving one or more molecules, characterized by spatial and energetic matching, constitute both the spatially active structural framework of traditional Chinese medicine constituents and the spatial arrangement lattice of their active atomic groups, thereby providing a fundamental chemical basis for elucidating the universal principles governing host–guest molecular interactions. ^[48,51] The group of active constituents in traditional Chinese medicine serves as the “imprinted template” assembly within this supramolecular system. Its bioactive components—including carbohydrates, amino acids, proteins, alkaloids, flavonoids, terpenes, volatile oils, and steroids—exhibit the characteristics of small-molecule “imprinted templates” while also undergoing complexation, coordination, and charge-transfer interactions to form supramolecular structures. Moreover, carbohydrates, amino acids, and nucleotides function as functional monomers to synthesize supramolecular polymers, thereby organizing the structural architecture. ^[48-50] Therefore, in traditional Chinese medicine, the various molecular components can interact with one another and with the organism to form biomolecular supramolecular complexes according to an “imprint template,” thereby exerting their therapeutic effects.

Take “pi ru pi” as an example: “Pi refers to the superficial layer of the meridians; when pathogenic factors invade the skin, the pores and collaterals open.” Herbal medicines of the “pi” category often contain highly dispersing aromatic volatile oils—what we may call an “imprinting template” functional group—which facilitate the ascending and dispersing of clear yang to the surface of the pores and collaterals. Further elaboration reveals that the pharmacological effects arise from the binding of this aromatic-volatile-oil “imprinting template” functional group with specific recognition sites on the skin’s imprint polymers and cavities. Moreover, since “the four limbs are the root of all yang,” the intensity of the “clear yang” effect exerted by the aromatic-volatile-oil “imprinting template” functional groups in branch-based herbs is generally weaker than that of the skin-based herbs. For instance, guizhi (the twig of cinnamon) has a weaker “clear yang” effect than rougui (cinnamon bark), yet it can unblock the meridians and disperse wind-cold from the nutritive level; moreover, it is lighter in texture, more ethereal in nature, and milder in flavor than rougui. This further corroborates the possibility that there are differences in both the types and contents of aromatic “imprinting template” compounds between skin-based and branch-based herbs. Supramolecular “imprinting templates” constitute the microscopic material basis underlying the fundamental theories of traditional Chinese medicine: when molecules with identical or similar “imprinting template” channel structures come together, they form the meridians and zang-fu organs; and when medicinal molecules bearing the same or similar “imprinting template” interact with these structures, they give rise to the active constituents of the herb. It is precisely through the imprinting interactions between these active constituents and the meridians and zang-fu organs that the theories of herbal properties and therapeutic effects are established.

The degree of variation in the pharmacological properties and therapeutic efficacy of “homologous but heteroeffective” traditional Chinese medicines depends on the extent of change in the “imprint template” of the host–guest system. Previous studies have shown that if significant differences are observed in the total statistical moments, information entropy, and biological entropy of the fingerprint profiles of such medicines, this suggests that their “imprint templates” may differ, thereby implying potential differences in their pharmacological properties and therapeutic effects. Zhu Zhifei et al. ^[52] Application of the segmental total-statistics moment method and information entropy to mulberry branches, mulberry leaves, mulberry bark, and mulberry fruits 4 of Weisangyuan medicinal materials High-Performance Liquid Chromatography Analysis of the fingerprint spectrum revealed that, over a specific time period, the second-order moment of the total quantity and the information entropy exhibited significant differences, indicating 4 Sangyuan medicinal materials may contain identical or similar constituents, but their respective contents and ratios, as well as the overall characteristics of their “imprinted templates,” may differ. In the future, preparative chromatography, molecular imprinting experiments, and pharmacodynamic studies can be employed to further elucidate the types and relative abundances of the “imprinted template” functional groups within specific fractionation ranges, as well as the differences between individual herbal components and the overall therapeutic efficacy of the traditional Chinese medicine formulation.

“Homologous yet different in efficacy” traditional Chinese medicines, to varying degrees, exhibit similar and dissimilar “imprint-template” interaction clusters. Upon entering the bloodstream, under the supramolecular “gas-extraction” effect, they bind to the meridians and zang-fu organs that possess the same spatial structural features of the “imprint template,” thereby eliciting imprinting effects. Moreover, the human body harbors a naturally interconnected metabolic enzyme network; within this network, the various constituents of traditional Chinese medicines are mutually linked, exchanged, and transmitted, with individual components capable of being metabolized into multiple metabolites. Both the parent compounds and their metabolites follow similar kinetic models, and the derivative groups of the same core scaffold’s active constituents can mutually inhibit, accelerate, and transform one another in vivo. Consequently, when a single core scaffold gives rise to multiple derivative constituents in traditional Chinese medicine, these derivatives produce similar metabolic products and pharmacological effects within the body. In contrast, active constituent groups derived from different core scaffolds, due to their greater divergence within the vast metabolic enzyme and effector network system, undergo longer-distance transmission and require extended cycles of transformation and regulation; thus, multiple derivatives stemming from different core scaffolds yield Different metabolites and pharmacological effects ^[53] By employing bioinformatics and computational biology approaches to analyze the topology of biological networks and calculating topological metrics such as characteristic path length, clustering coefficient, network diameter, average node degree, degree distribution, and network density, it is possible to characterize the “multi-component, holistic, and dynamic” network features of traditional Chinese medicine pharmacokinetics. ^[54-55] . Our research group previously developed a mathematical model of network dynamics. ^[54-58] , thereby providing a framework for research on the network pharmacokinetics and pharmacodynamics of “same origin, different effects” traditional Chinese medicines.

In addition, metabolic clusters can be delineated by calculating the structural similarity between parent compounds and their metabolic derivatives, thereby identifying “fingerprint template” groups, which is of great significance for elucidating the material basis of “homologous but different effects” in traditional Chinese medicines. In previous studies, This research group It was found that by calculating the molecular connectivity indices of prototype products and metabolites ( molecular connectivity index ， MCI ) By identifying their structural characteristics and then applying the cosine similarity method to calculate similarity, the “imprint template” among their metabolites can be characterized. Zhou Yanzǐ et al. ^[59] A study was conducted on the universal “imprinting template” for metabolites of Houttuynia cordata volatile oil using an in vitro metabolic model, and the results showed that a total of Houttuynia cordata volatile oil metabolites were obtained. 62 One, among which there are common components. 6 namely tetradecane, phytane, decanoic acid, caproic acid, isobornyl acetate, and n-hexanol; with the exception of isobornyl acetate, MCI Similarity to the overall metabolites ( 0.914 ~ 0.964 ) is relatively high, indicating that these common components are highly representative of the overall metabolites and may be the potential active constituents responsible for the pharmacological effects. By categorizing the non-common components, we obtain 6 a component group, whose average MCI and total metabolites MCI the similarity ( 0.939 ~ 0.999 ) are all relatively high; however, the average among the various component groups MCI The differences in similarity are significant: while the overall structure within each component group is broadly similar, distinct differences exist among the groups, suggesting their independence. In summary, this 6 This component group can serve as an “imprinting template” that represents the universal metabolic targets of Houttuynia cordata volatile oil, and provides a reference for identifying “imprinting templates” of traditional Chinese medicines with “homologous but different effects.”

Supramolecules formed through the binding of supramolecular hosts and guests within the human body’s meridians and zang-fu organs can alter the properties of both host and guest molecules. On a macroscopic level, this manifests as the migration of small molecules within the host molecule and anisotropic physicochemical properties; concurrently, the physicochemical properties of the host molecule itself also undergo changes. The “lock-and-key” relationship between host and guest molecules can be characterized by the specific “imprinted template” interaction patterns that act upon particular zang-fu organs and meridians. Therefore, it is theoretically feasible to apply the supramolecular chemistry concept of “imprinted templates” to investigate the phenomenon of “homologous but different effects” in traditional Chinese medicines.

4   Conclusion

The phenomenon of “same origin, different effects” was first documented in the “Biographies of Famous Physicians” from the Qin and Han dynasties. At its core, it stems from the clinical observations and summaries made by ancient practitioners, who, based on the observed therapeutic effects, deduced the principle of “analogical reasoning” and attributed to such herbs the functional characteristics of “analogical reasoning,” thereby embodying the diagnostic and differential-thinking approach of traditional Chinese medicine. Herbs exhibiting “same origin, different effects” primarily include 3 Three scenarios: Chinese medicinal materials from different parts with different therapeutic effects; Chinese medicinal materials from the same part at different stages of maturity with different therapeutic effects; and Chinese medicinal materials from the same part before and after processing with different therapeutic effects, among which the first... 1 This situation accounts for a substantial proportion. The main research approaches to the phenomenon of “same origin, different effects” in drug use include pharmacognostic verification and the study of their patterns of application. Pharmacognostic verification can determine whether the criteria of “same origin” are met by examining the botanical origin, nomenclature, geographic origin, and processing methods of Chinese medicinal materials, thereby enabling an in-depth exploration of the “homologous” relationships among herbs with “same origin but different effects.” It also involves investigating the differences in the characteristics, odor, properties, and functions and indications of these herbs, as well as comparing the extent of their “different effects.” Meanwhile, studies on the material basis can elucidate the mechanisms underlying the “different effects,” thus guiding clinical medication.

Although numerous studies have been conducted on the “same origin, different effects” phenomenon, yielding substantial progress, a systematic explanation of this pharmacological pattern has yet to be established. Current research on such herbs generally fails to integrate micro-level mechanisms with macro-level theoretical frameworks, thereby limiting their clinical relevance. In contrast, the foundational theories of Traditional Chinese Medicine emphasize that the human body is constituted by qi, which serves as the fundamental substance sustaining life: “Essence, qi, body fluids, blood, and the meridians are all transformations of qi.” The human body is an active, dynamic organism in which continuous processes of form–qi transformation—such as ascending, descending, entering, and exiting—are constantly at work; this conceptualization is, in essence, aligned with the supramolecular “imprinting template” self-organization theory. Upon entering the body, “same origin, different effects” herbs, under the influence of supramolecular gas-extraction interactions, release “imprinting templates” that exert their therapeutic effects through “lock-and-key” binding. These “imprinting templates” constitute the material basis of the herbs. By summing the fingerprint profiles of “same origin, different effects” herbs and applying total-quantity statistical moment analysis, it becomes possible to identify their characteristic “imprinting templates.” Subsequently, network metabolic analysis based on the principle of network resonance reveals both the similarities and differences in the mechanisms underlying the actions of these herbs. Therefore, the supramolecular chemistry theory of “imprinting templates” can offer new perspectives for research on “same origin, different effects” herbs and provide valuable guidance for related studies.