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2024 Volume 3
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Abstract
Introduction
Bioactive components and pharmacological effects of E. ulmoides
Distribution and harvesting of the bioactive components of E. ulmoides
Synthesis and genetic regulation of the bioactive components of E. ulmoides
Genetic variation and breeding of superior E. ulmoides varieties
Problems and prospects
Author contributions
Data availability
Acknowledgments
Conflict of interest
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Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides

  • State Key Laboratory of Tree Genetics and Breeding, National Engineering Research Center of Tree Breeding and Ecological Restoration, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

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  • Eucommia ulmoides, a tertiary relict plant species, remains the only extant representative of both the genus Eucommia and the family Eucommiaceae. With a history of more than two millennia of use in traditional Chinese medicine, its bark, leaves, and fruits harbor a diverse array of bioactive compounds, including flavonoids, iridoids, lignans, and phenylpropanoids. These compounds have various effects, such as regulating blood pressure, preventing osteoporosis, providing neuroprotection, modulating the immune system, and exhibiting antimicrobial and antiviral activities, as well as improving hypoxia tolerance and reducing lipid levels. In recent years, significant advancements have been made in the identification of bioactive components, pharmacological research, understanding the genetic basis of biosynthesis, breeding of new varieties, and the development of efficient cultivation techniques. These advancements have positioned Eucommia as a species with an extensive range of research interests. However, several challenges persist in the advanced development of Eucommia. These include insufficient research on pharmacological mechanisms, limited genetic diversity, and prolonged traditional cultivation cycles. To overcome these challenges, future research efforts should focus on breaking these bottlenecks by selecting high-yield, high-quality varieties through a combination of conventional and unconventional breeding methods. Additionally, integrating intensive cultivation techniques with comprehensive utilization strategies is crucial. Promoting the establishment of a green circular economy centered around the active ingredients of Eucommia can further enhance the economic benefits of the Eucommia industry.

  • Introduction

    Eucommia ulmoides (E. ulmoides), a tertiary relict species belonging to the family Eucommiaceae, is a monotypic genus with a chromosome count of 2n = 2X = 34. It is a versatile economic tree species endemic to China. Its distribution is primarily concentrated in the middle and lower reaches of the Yangtze River in China[1,2]. E. ulmoides likely exhibited broad adaptability in its evolutionary history[3]. Fossil evidence indicates that primitive E. ulmoides had a widespread distribution during the Miocene epoch, spanning nearly the entire Northern Hemisphere, but became restricted to central China following the Quaternary glaciation[4]. Consequently, this species can be introduced and cultivated in numerous regions worldwide. Presently, it is cultivated extensively across a vast geographic range in China, including between latitudes 22° N and 42° N and longitudes 100° E to 121° E, encompassing a planting area exceeding 400,000 hectares. This accounts for more than 99% of the global E. ulmoides resources[5]. Furthermore, the species has been successfully introduced to countries such as the United States, the United Kingdom, France, Ukraine, Russia, Australia, Japan, and South Korea.

    E. ulmoides, a traditional and esteemed Chinese medicinal herb has a medicinal history spanning over two millennia (Fig. 1a). It was classified as a superior herb in the Han Dynasty's 'Shennong Ben Cao Jing' and is renowned for its antiaging properties[5]. Modern research has identified biologically active substances such as chlorogenic acid, aucubin, geniposidic acid, and geniposide in its bark, leaves, and fruits, which contribute to its efficacy in regulating blood pressure, preventing osteoporosis, improving neuroprotection, immune modulation, and antimicrobial and antiviral activities, enhancing hypoxia tolerance, and lowering blood lipids[1,2,5−7]. Furthermore, E. ulmoides shows promise as a temperate tree species for industrial gum production because its leaves contain 2%−3% gum (Fig. 1c), its bark contains 10%−12% gum (Fig. 1b), and its fruits contain 10%−18% gum[1,2]. The gum from E. ulmoides shares the same chemical composition as natural rubber but differs in its chemical structure, being trans-polyisoprene, which lacks elasticity. However, when modified, this compound combines the dual properties of rubber and plastic. It can be processed into sulfur-cured elastic rubber, like Hevea rubber, and possesses unique features such as low-temperature shape memory[8,9]. This finding demonstrates the extensive versatility and immense value of E. ulmoides, as every part of the plant is valuable. It shows significant potential for application and development in medicine, food, and the gum industry, as well as in materials, urban and rural landscaping, and soil and water conservation.

    Figure 1.  Characteristics of the E. ulmoides, bark, and leaves. (a) The morphology of the adult E. ulmoides. (b) Gums contained in the bark of E. ulmoides. (c) Gums contained in the leaf of E. ulmoides.
    DownLoad: Full-Size Img PowerPoint

    Since the 1950s, because of the significant development value of E. ulmoides in pharmaceuticals and rubber production, research has increasingly focused on pharmacological effects; extraction and identification of active components; rubber and drug manufacturing; germplasm resources; seedling breeding; introduction and cultivation; genetic foundation; and selection of improved varieties[1,2]. E. ulmoides has become one of the most widely studied and highly regarded tree species globally. Building on existing research, it is crucial to address and overcome the theoretical and technical bottlenecks in the development and utilization of E. ulmoides resources. Enhancing the precision and efficiency of industrial development, reducing the production costs of rubber and pharmaceuticals, and promoting the development of a green circular economy centered on the active components of E. ulmoides are vital goals. These efforts aim to meet the significant demands of human economic development and health. This review aims to provide a comprehensive overview of recent advancements in the identification, distribution, synthesis, and genetic regulation of bioactive components in E. ulmoides. It also seeks to explore the challenges and issues associated with the industrial application of these active ingredients and to propose future research directions. Ultimately, the goal is to offer significant references for the sustainable industrial utilization of E. ulmoides.

    Bioactive components and pharmacological effects of E. ulmoides

    Modern medical research has shown that the medicinal value of E. ulmoides is associated primarily with the rich bioactive components found in its bark, leaves, male flowers, and seeds. To date, more than 200 compounds have been isolated from various parts of E. ulmoides, with the leaves containing the greatest variety and quantity of bioactive components, followed by the male flowers, with relatively fewer in the bark and seeds. These components include mainly flavonoids, iridoids, lignans, phenylpropanoids, phenolic acids, terpenes, and steroids[5,7,10] (Table 1). The flavonoids in E. ulmoides include quercetin, rutin, astragulin, kaempferol, hyperoside, isoquercitrin, catechin, and others, most of which are flavonoids of the quercetin and kaempferol glycoside types. Present lignans are mostly glycosides, including pinoresinol, olivine, dehydrodiconiferyl alcohol, and directed lipoxyglucoside, with the major component being pinoresinol diglucoside (PDG). Present iridoids are primarily monoterpene compounds, such as geniposidic acid, aucubin, asperuloside, harparin acetate, ajugoside, eucommiol, and reptoside. Phenylpropanoids have a C6-C3 structure and are precursors to lignans and flavonoids, including chlorogenic acid, caffeic acid, isochlorogenic acids A and C, guaiacylglycerol, and cobrazin[5,7,10]. Research has shown that E. ulmoides is rich in many bioactive components with high utilization values.

    Table 1.  Key active components, main existing parts, and pharmacological effects of E. ulmoides.
    Compound name Molecular formula Molecular structural formula Main existing parts Pharmacology Ref.
    Phenolic acid monomer compounds Chlorogenic acid C16H18O9 Leaves, bark, fruit pods, male flowers Antioxidant,
    anti-inflammatory,
    anti-tumor, etc    		 [11]
    Protocatechuic acid C7H6O4 Leaves, bark, fruit pods, male flowers [12]
    Caffeic acid C9H8O4 Leaves, bark, fruit pods, male flowers [13]
    Cyclohexene ether terpenes Geniposidic acid C16H22O10 Leaves, bark, fruit pods, male flowers Anti-inflammatory, promoting wound healing, diuresis, etc. [13]
    Aucubin C15H22O9 Leaves, bark, fruit pods, male flowers [14]
    Asperuloside C18O11H22 Leaves, bark, fruit pods, male flowers [13]
    Geniposide C17H24O10 Leaves, bark, male flowers [13]
    Flavonoids Quercetin C15H10O7 Leaves, fruit pods, male flowers Antioxidant, blood lipid-lowering, anti-allergy, anti-inflammatory, antiviral, anticancer, etc.
    		 [12]
    Kaempferol C15H10O6 Leaves, fruit pods, male flowers [11,15]
    Rutin C27H30O16 Leaves, bark, fruit pods, male flowers [11]
    Astragalin C21H20O11 Leaves, male flowers [11]
    Hyperoside C21H20O12 Leaves, bark [16]
    Catechin C15H14O6 Leaves, bark, fruit pods, male flowers [17]
    Lignans Pinoresinol C20H22O6 Leaves, bark Blood pressure-lowering, neuroprotective, etc. [18]
    Olivil C20H24O7 Leaves, bark [18]
    Pinoresinol diglucoside C32H42O16 Leaves, bark, fruit pods, male flowers [13]
     | Show Table
    DownLoad: CSV

    Ancient Chinese medical practices and modern pharmacological studies have indicated that E. ulmoides contains several important bioactive components with various beneficial effects, including blood pressure regulation, osteoporosis prevention, neuroprotection, immune modulation, and antibacterial and antiviral properties[1,2,5,7]. Among these compounds, lignan compounds such as pinoresinol diglucoside, dehydrodiconiferyl alcohol, and pinoresinol monoglucoside; phenylpropanoid compounds such as chlorogenic acid and caffeic acid; iridoid compounds such as geniposidic acid, geniposide, and aucubin; and flavonoid compounds such as quercetin and rutin all exhibit blood pressure-regulating effects. The mechanisms involve promoting nitric oxide (NO) release and inhibiting angiotensin II, calcium (Ca2+) influx, and phosphodiesterase synthesis[19−21]. E. ulmoides compounds such as pinoresinol diglucoside, kaempferol, rutin, quercetin, and geniposidic acid can promote osteoblast formation[22,23], whereas aucubin can prevent steroid hormone-induced osteoblast apoptosis, thereby helping to prevent osteoporosis[24]. Lignans from E. ulmoides bark, geniposide, and aucubin also have neuroprotective effects, such as inhibiting acetylcholinesterase activity to protect ganglion cells from damage[25], reducing the loss of dopaminergic neurons[26], and alleviating neuroinflammatory responses[27]. These compounds are potentially beneficial in treating neurodegenerative diseases such as glaucoma, Parkinson's disease, epilepsy, and Alzheimer's disease. Additionally, extracts from E. ulmoides bark and leaves exhibit varying degrees of inhibition against fungi such as Candida albicans and bacteria such as Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium[28,29]. Compounds such as chlorogenic acid and caffeic acid from E. ulmoides have been shown to protect HIV-infected cells from pathological changes to a certain extent[30]. Furthermore, pinoresinol monoglucoside inhibits H1N1 virus[31]. In the realm of pharmacological effects, the leaves and bark of E. ulmoides exhibit similar activities, which include antioxidant, hypoglycemic, and hypotensive properties[32]. However, there may be differences in the intensity and efficacy of certain pharmacological actions between the two. For instance, the leaves of E. ulmoides are more prominent in antioxidant activity, while the effects of mature leaves are superior to those of tender and old leaves in terms of central sedation, and also superior to the bark[32]. The outcomes of modern pharmacological research have illuminated the direction for the in-depth development and utilization of E. ulmoides resources. The specific pharmacological effects of E. ulmoides fruit have not been extensively discussed in existing evidence, and future research can further explore the pharmacological effects of the fruit and its differences and connections with the leaves and bark of E. ulmoides.

    Distribution and harvesting of the bioactive components of E. ulmoides

    The bark, leaves, male flowers, and seeds of E. ulmoides all contain bioactive components, but there are significant differences in the concentrations of these components across different tissues and organs[9,10,33−35]. In general, the leaves of E. ulmoides are rich in flavonoids, iridoids, phenolic acids, terpenoids, and steroids[32]. The male flowers primarily contain iridoids, flavonoids, and triterpenoids. Seeds are rich in iridoids, whereas bark has the highest content of lignans[4,5,8,33,36]. Flavonoids are relatively most abundant in the leaves, followed by the male flowers, with lower concentrations in the bark and seeds[8,33,34,36]. The determination of total flavonoids in E. ulmoides leaves, male flowers, bark, and seeds collected from various regions in China, such as Hanzhong in Shaanxi, Yichang in Hubei, and Changzhi in Shanxi, revealed that their average contents decreased in the following order: 9.02%, 3.02%, 1.33%, and 1.22%, respectively[34]. The measurement of the total flavonoid content of various tissues and organs at different growth stages revealed that mature leaves presented the highest total flavonoid content, which was significantly different from that of young leaves. In contrast, the flavonoid contents in branches, trunks, bark, and roots at different parts or developmental stages show little variation[35]. Phenylpropanoid components are most abundant in the leaves, followed by the fruit pods, with the lowest content in the bark[9,10,32]. For example, chlorogenic acid is present in all parts of E. ulmoides, but its content in the leaves is the highest, reaching approximately 2.5%[10,33,36,37]. Lignan components are most abundant in the bark, followed by the leaves, and are least abundant in the fruit pods. For example, the content of pinoresinol diglucoside in dried bark is approximately 0.5%, which is significantly greater than that in other parts[10,33,36,38]. Iridoid components are most abundant in the fruit pods, followed by the bark and male flowers, with relatively lower leaf content. For example, the content of geniposidic acid in the leaves of E. ulmoides is approximately 1.5%, whereas in the bark of branches, it can reach up to 6.71%[10,33,36]. The spatial and temporal distribution characteristics of bioactive components in E. ulmoides suggest that in the industrial development process of this plant, it is necessary to determine the direction of utilization of different organs and tissues and the corresponding cultivation and utilization methods according to the differences in the content of the main active components.

    Research indicates that as the age of E. ulmoides trees increases, the contents of flavonoids and phenylpropanoids in the leaves tend to decrease, whereas the content of lignans increases. Conversely, the contents of lignans and protocatechuic acid in the branch bark and trunk bark of E. ulmoides tend to increase[33]. Moreover, the active components of E. ulmoides vary depending on the harvest time. For example, the total flavonoid content in E. ulmoides leaves is highest in April and May, decreases in June and July, and then slightly increases and then stabilizes after that. Consequently, this suggests that the optimal time for harvesting leaves is April and May[35]. Notably, variations in the contents of the bioactive components of E. ulmoides can be attributed to differences in planting location, tree age, organ or tissue, developmental stage or position, and preservation and processing methods[10,33,35,39−41]. This results in different optimal harvesting times; for example, the highest average content of chlorogenic acid in E. ulmoides leaves was observed in July in Zhangjiajie, Hunan, China[39], whereas in Xi'an, the highest content was found in August and September[30]. The significant differences in the bioactive component contents and optimal harvesting times of E. ulmoides are likely due to variations in the natural environments of different planting locations[10,41].

    Additionally, there are differences in the bioactive components between leaves from current-year seedling forests and those from arboreal forests. Compared with those from arboreal forests, the leaves from current-year seedling forests contain significantly greater levels of various active components, such as total flavonoids, chlorogenic acid, geniposidic acid, aucubin, and pinoresinol diglucoside. These levels were several times greater than those of E. ulmoides leaves collected from arboreal forests at the same time, indicating substantial potential for wider application[36]. Importantly, newly emerged young leaves accumulate lower levels of bioactive components. Harvesting in a leaf-oriented tree model should be based on changes in the bioactive component contents of the leaves. This can be accomplished by selecting leaves of suitable age for batch harvesting or by performing concentrated coppicing when most leaves have matured.

    Synthesis and genetic regulation of the bioactive components of E. ulmoides

    E. ulmoides has achieved high-quality chromosome-level genome assembly and functional annotation via a haploid approach[42]. Concurrently, studies have been conducted on the key enzymes involved in the synthesis of bioactive components such as lignans, phenylpropanoids, terpenoids, and flavonoids, as well as their genetic regulation. Lignans are the principal medicinal compounds in E. ulmoides, whereas lignin plays a role in the plant's defense against pests and diseases. Both lignans and lignin share the common precursor pineol. Research indicates that the formation of pinoresinol is a critical step in the biosynthetic pathway of lignans[43]. The dirigent protein oxidase (DIR)-encoding gene plays a critical role in the biosynthesis of lignans[44]. The transcriptome of E. ulmoides contains 58 unigenes encoding the ten key enzymes involved in the biosynthetic pathways of lignans and lignin. These unigenes encompass critical processes in the biosynthesis of lignans and lignin in E. ulmoides. The expression levels of 4-coumarate-CoA ligase (4CL), hydroxycinnamoyl-CoA (HCT), cinnamoyl CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), caffeoyl-CoA 3-O-methyltransferase (CCoAOMT), DIR, and peroxidase (POD) are greater in the stem than in the leaves, whereas PAL and C4H are expressed at higher levels in the leaves than in the stem[44].

    The primary flavonoids in E. ulmoides are quercetin and kaempferol[45]. The biosynthetic pathways of these two bioactive substances are highly similar. Initially, phenylalanine is converted into p-coumaroyl-CoA by phenylalanine ammonia-lyase (PAL) and 4-coumaroyl-CoA ligase (4CL). This process is subsequently catalyzed by chalcone synthase (CHS) to produce chalcone, which is then converted into naringenin by chalcone isomerase (CHI). Naringenin undergoes consecutive catalysis by flavanone 3-hydroxylase (F3H) and flavonoid 3'-hydroxylase (F3'H) to form dihydroquercetin, which ultimately transforms into quercetin[46]. Additionally, dihydrokaempferol can be directly converted into kaempferol by flavonol synthase (FLS)[47]. Studies have shown that there are three and four family members of CHS and E. ulmoides FLS, respectively, in E. ulmoides. In contrast, CHI and flavanone F3H are highly conserved, with only one gene identified in both the fruits and leaves of E. ulmoides[48]. The gene expression of these two enzymes shows significant tissue specificity. For example, within the CHS gene family, EuCHS1 is expressed primarily in the leaves, whereas EuCHS2 is expressed mainly in the fruits[48]. In the FLS gene family, EuFLS3 and EuFLS4 have much higher expression levels in leaves than in young fruits, whereas EuFLS1 and EuFLS2 show the opposite trend[48]. Transcription factors such as MYBs and bHLHs may play crucial regulatory roles in the flavonoid synthesis and phenylpropanoid synthesis pathways in E. ulmoides leaves[49].

    The main phenylpropanoid compound is chlorogenic acid[50]. Three biosynthetic pathways for chlorogenic acid have been identified in plants[51]. The latest genome data for E. ulmoides indicate that only two pathways are involved in the biosynthesis of chlorogenic acid[42]. One pathway involves the hydroxylation of p-coumaroylquinic acid by p-coumaroylquinic acid/shikimate 3′-hydroxylase (C3′H)[52], and the other pathway involves synthesis from caffeoyl-CoA and quinic acid catalyzed by hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (HQT)[53]. In the E. ulmoides genome, 23 candidate genes related to six key enzyme-encoding gene families involved in the chlorogenic acid biosynthesis pathway were identified. These genes included seven PAL genes, eight 4CL genes, two C4H genes, two C3'H genes, one HCT gene, and three HQT genes[42]. Analysis of gene expression profiles in leaves and bark revealed that the expression levels of PAL (PAL2 and PAL5), C3'H2, C4H6, HQT2, and HCT are significantly greater than those of other genes[42]. Some transcription factors (TFs) from the MYB, ZIP, ERF, and WRKY families may be involved in regulating the biosynthesis of chlorogenic acid in E. ulmoides[54].

    The biosynthetic pathway of terpenoids in plants can generally be divided into three stages: the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids, which synthesize the five-carbon skeleton isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP)[55,56]. DMAPP and IPP, under the catalysis of geranyl diphosphate synthase (GPS), synthesize geranyl diphosphate (GPP). GPP is then converted to farnesyl diphosphate (FPP) under the catalysis of farnesyl diphosphate synthase (FPS), and finally, geranylgeranyl diphosphate (GGPP) is synthesized under the catalysis of geranylgeranyl diphosphate synthase (GGPS)[57]. Under the action of various terpenoid synthases and modifying enzymes, structurally and functionally specific terpenoid compounds are produced[58]. In E. ulmoides, 13 genes involved in the six reactions of the MVA pathway and 11 genes involved in the seven reactions of the MEP pathway were identified. Additionally, the genes involved in the catalytic synthesis of FPP, GPP, and GGPP include three GPS genes, seven GGPS genes, and four FPS genes[42]. HMGR is the first rate-limiting enzyme in the MVA pathway and serves as a crucial regulatory point in cytoplasmic terpenoid metabolism[58]. Members of the EuHMGR gene family in the MVA pathway, along with other genes such as EuMK, EuPMK, and EuMDP, show significant differential expression in young and mature fruits of E. ulmoides[59].

    Genetic variation and breeding of superior E. ulmoides varieties

    Currently, natural forests of E. ulmoides are extremely rare, with only a few ancient trees occasionally found in their original habitats[60,61]. Although E. ulmoides is cultivated primarily in plantations, its dioecious nature and cross-pollination, coupled with seed propagation, result in significant trait variation both within and between half-sibling and full-sibling families[62,63]. Therefore, the species still maintains relatively rich genetic diversity within its populations, with the semiwild population in Shennongjia exhibiting a relatively high level of genetic diversity[62−66]. E. ulmoides exhibits rich morphological variation, with genetic differences observed in traits such as bark, leaves, branches, and fruits, leading to the formation of unique natural types. For example, bark characteristics can be categorized into smooth-barked and rough-barked types. Leaf shape variations can be classified into types such as small leaves, long leaves, and dense leaves, among others[1,2,66−68]. Under the influence of different environmental selection pressures across its vast cultivation areas, E. ulmoides has developed various geographic provenances. These geographic provenances differ in terms of leaf and seed morphology; Eucommia rubber; and the contents of bioactive compounds, such as aucubin, chlorogenic acid, total flavonoids, geniposidic acid, and geniposide[66,69,70]. Notably, E. ulmoides from southern Shaanxi, northeastern Sichuan, northwestern Hunan, and northwestern Guizhou are considered superior provenances[66].

    Cross-pollination in E. ulmoides results in abundant genetic variation within the species, allowing significant results to be achieved by directly selecting for natural variations. Currently, a series of superior varieties, such as 'Huazhong' and 'Qinzhong', have been selected from natural populations. These varieties are characterized by fast growth and high yields of leaves, male flowers, samaras, and effective compounds[71−76], thereby promoting the improvement of E. ulmoides cultivars. Because E. ulmoides is a relict tree species that is dioecious and wind-pollinated, the superior types found in nature are themselves products of intraspecific hybridization. Elite trees bred through intensive selection from large natural populations should exhibit greater genetic gains. Consequently, the difficulty of breeding new, improved E. ulmoides varieties through simple parental hybridization is very high, making it challenging to surpass the existing selected varieties. Due to the doubling of chromosome numbers, polyploid plants often exhibit significant morphological and physiological changes, such as increased cell volume, larger and thicker leaves, and higher metabolite content. Therefore, polyploid breeding has always been a promising approach for the genetic improvement of E. ulmoides[2]. Researchers have conducted extensive studies on the doubling of chromosomes in both somatic and germ cells of this species. These studies include inducing triploidy through endosperm culture[77], treating germinating seeds and seedling growth points with colchicine solution to induce tetraploidy[78,79], and doubling pollen chromosomes[80,81]. Additionally, a series of triploid E. ulmoides plants were successfully obtained by inducing the doubling of chromosomes in female gametes through high-temperature treatment[82,83]. These triploid E. ulmoides plants often exhibit excellent characteristics, such as larger leaves, faster growth, and significantly increased contents of Eucommia rubber and medicinal components[84], highlighting the potential for the genetic improvement of E. ulmoides.

    Problems and prospects

    The bark of E. ulmoides has been a well-established medicinal herb for centuries; however, the utilization of other plant parts has not been as extensively explored. Unlike the bark, the leaves of E. ulmoides are a renewable resource that is abundantly available. Therefore, the efficient exploitation of E. ulmoides leaves is crucial for the sustainable exploitation of this plant's resources. In 2005, the leaves of E. ulmoides were officially recognized in the Chinese Pharmacopoeia. Subsequent studies have revealed that these leaves contain a plethora of physiologically active compounds, often in higher concentrations than those present in the bark. Moreover, in terms of pharmacological efficacy, the leaves and bark of E. ulmoides have been found to possess comparable potency[41]. In 2023, the leaves of E. ulmoides were officially included in the catalog of substances recognized as both food and traditional Chinese medicinal materials by the National Health Commission and the State Administration for Market Regulation of China. This recognition has opened up significant opportunities for the research, development, and application of E. ulmoides leaves across diverse industries, including pharmaceuticals, food products, dietary supplements, animal feed additives, and chemical products.

    In reviewing current research, development, and utilization of the bioactive components of E. ulmoides, significant milestones have been achieved through collaborative endeavors of all scientific researchers and industrial developers. These advancements encompass the identification of bioactive compounds and their pharmacological properties, the genetic underpinnings of biosynthesis, the spatiotemporal distribution characteristics of these components, the implementation of efficient agricultural practices, the cultivation of new varieties, and the development of comprehensive extraction techniques. These breakthroughs have laid a foundational framework for the comprehensive development of the E. ulmoides industry, contributing to the promotion of the entire industrial chain for E. ulmoides. However, it is important to recognize that current research on the bioactive substances of E. ulmoides still faces several restrictive challenges, which hinder its development and efficient utilization. For instance, current pharmacological research is predominantly confined to ethanol or water extracts of mixed components from E. ulmoides. While these extracts have shown notable pharmacological activities in areas such as antioxidant effects, blood pressure reduction, and lipid-lowering, studies on individual components are comparatively limited, and there is a significant lack of in-depth research and understanding of the synergistic effects among the various components. Although the genome sequencing of E. ulmoides has been completed, the genetic regulatory mechanisms of most of its bioactive components are still not clearly understood, primarily due to the lack of an established system for ex vitro regeneration and genetic function validation of E. ulmoides. Research on allelic variations related to relevant traits is rare, and there is a need to enhance the supportive role of basic research in breeding and its applications. The limited size of the remaining wild populations of E. ulmoides trees restricts the effectiveness of simple crossbreeding; despite breakthroughs in polyploid breeding, these advancements still depend on a somewhat random selection of parent varieties, indicating a substantial room for improvement in seed selection. The traditional cultivation of E. ulmoides as a tree crop involves long cycles, and the mechanization of harvesting is challenging, leading to high labor costs for raw material collection. Meanwhile, the cultivation model for leafy forests is still in the early stages of exploration. The utilization of bioactive substances from E. ulmoides is rudimentary, and the benefits are minimal; a comprehensive strategy for the preparation and utilization of various types of bioactive compounds has yet to be fully developed, which represents a key challenge for future industrial applications.

    Thus, it is imperative to fully acknowledge and address the restrictive challenges hindering the development of the E. ulmoides industry. Focused efforts should be directed toward key medicinal properties and other major target traits, emphasizing efficient detection, and precise assessment of active ingredients in E. ulmoides. This approach should build upon the comprehensive collection and preservation of superior genetic resources of E. ulmoides, exploring advanced techniques for high-throughput screening and accurate evaluation of active components. Research initiatives should also delve into population genetic diversity, allelic variation patterns of key traits, regulatory networks of genes related to target traits, distinctive gene expression characteristics, and their genetic effects. Such endeavors will effectively promote the integration of conventional breeding with unconventional approaches such as chromosome doubling, genetic transformation, or gene editing, aiming to cultivate new E. ulmoides varieties characterized by high yields and elevated levels of medicinal components. Moreover, enhancing the foundational work on the isolation, purification, and pharmacology of key active compounds in E. ulmoides is crucial. This includes comprehensive research on the mechanisms of action of individual active compounds and their synergistic effects when used in combination, thereby establishing a robust basis for the development of E. ulmoides-derived biopharmaceuticals. Furthermore, there is a pressing need to enhance the foundational work related to the separation, purification, and pharmacological investigation of the key active components of E. ulmoides, particularly regarding the mechanisms of action of individual bioactive compounds. A comprehensive understanding of the synergistic effects among various active ingredients and their collective impact on human and animal physiology is equally imperative. Such efforts are essential for establishing a robust foundation for the development of biopharmaceuticals derived from E. ulmoides.

    By adopting superior varieties, ultrashort-cycle leaf forest cultivation, and mechanized harvesting, raw material costs can be significantly reduced. Additionally, the comprehensive utilization of different plant parts will help distribute raw material costs more effectively. Specifically, leaf veins and bark can be used for gum production and extraction of medicinal compounds, whereas leaf mesophyll can be utilized for pharmaceutical production or as a feed additive or health supplement. The stems can be used for manufacturing particleboard, reconstituted wood, or as substrates for edible fungi, thereby achieving multiple benefits from a single source of raw material. Resolving these issues will undoubtedly catalyze the efficient development of a green circular economy centered on E. ulmoides, with a primary focus on pharmaceutical and rubber production. This advancement will propel the E. ulmoides industry into a new phase of accelerated growth, fostering sustainable innovation and economic progress.

  • The authors confirm contribution to the paper as follows: writing - original draft preparation: Li Y; writing - review & editing: Kang X. Both authors reviewed the results and approved the final version of the manuscript.

  • Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

    • Acknowledgments

    This work was supported by the National Natural Science Foundation of China (32301620) and the Eucommia ulmoides series new varieties from Beijing Forestry University's horizontal projects.

  • The authors declare that they have no conflict of interest.

  • [1]

    Li FD, Du HY. 2001. Eucommia ulmoides. Beijing: China Press of Traditional Chinese Medicine
    [2]

    Kang XY. 2017. Status and prospect of improved variety selection in Eucommia ulmoides. Journal of Beijing Forestry University 39(3):1−6

    doi: 10.13332/j.1000-1522.20160377

    CrossRef   Google Scholar

    [3]

    Wuyun TN, Wang L, Liu H, Wang X, Zhang L, et al. 2018. The hardy rubber tree genome provides insights into the evolution of polyisoprene biosynthesis. Molecular Plant 11(3):429−42

    doi: 10.1016/j.molp.2017.11.014

    CrossRef   Google Scholar

    [4]

    Zhou ZhK, Arata M. 2005. Fossil history of some endemic seed plants of East Asia and its phytogeographical significance. Acta Botanica Yunnanica 27(5):449−70

    doi: 10.3969/j.issn.2095-0845.2005.05.001

    CrossRef   Google Scholar

    [5]

    Du H, Hu W, Yu R. 2013. Green book on the Eucommia industry: a report on China's Eucommia rubber resources and industry development. China: Social Sciences Academic Press. 384 pp
    [6]

    Zhang M, Liang FN, Sun YW, et al. 2023. Research progress on chemical constituents, pharmacological effects and clinical application of Eucommia ulmoides. Chinese Traditional and Herbal Drugs 54(14):4740−61

    Google Scholar

    [7]

    Xing YF, He D, Wang Y, Zeng W, Zhang C, et al. 2019. Chemical constituents, biological functions and pharmacological effects for comprehensive utilization of Eucommia ulmoides Oliver. Food Science and Human Wellness 8(2):177−88

    doi: 10.1016/j.fshw.2019.03.013

    CrossRef   Google Scholar

    [8]

    Li D, Yang C, Huang Y, Li L, Han W, et al. 2022. Novel green resource material: Eucommia ulmoides gum. Resources Chemicals and Materials 1(1):114−28

    doi: 10.1016/j.recm.2022.01.005

    CrossRef   Google Scholar

    [9]

    Zhang JC, Xue ZH, Yan RF, Fang SB. 2011. Natural polymer material—recent studies on Eucommia ulmoides gum. Acta Polymerica Sinica 10:1105−16

    Google Scholar

    [10]

    Zeng M, Long YQ, Zeng J, Yang M, Zhou XR, et al. 2023. Comparison of chemical constituents in different parts of Eucommiae Cortex. Chinese Traditional Patent Medicine 45(4):1184−94

    Google Scholar

    [11]

    Takamura C, Hirata T, Yamaguchi Y, Ono M, Miyashita H, et al. 2007. Studies on the chemical constituents of green leaves of Eucommia ulmoides Oliv. Journal of Natural Medicines 61(2):220−21

    doi: 10.1007/s11418-006-0027-5

    CrossRef   Google Scholar

    [12]

    Nakamura, T, Nakazawa, Y, Onizuka S, Satoh S, Chiba A, et al. 1997. Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves): 1. The clastogen-suppressing effects of Tochuu tea in CHO cells and mice. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 388(1):7−20

    doi: 10.1016/s1383-5718(96)00096-4

    CrossRef   Google Scholar

    [13]

    Deyama T, Ikawa T, Kitagawa S, Nishibe S. 1987. The constituents of Eucommia ulmoides Oliv. V. Isolation of dihydroxydihydrocinnamyl alcohol isomers and phenolic compounds. Chemical and Pharmaceutical Bulletin 35(5):1785−89

    doi: 10.1248/cpb.35.1785

    CrossRef   Google Scholar

    [14]

    Bianco, A, Iavarone, C, Trogolo, C. 1974. Structure of eucommiol, a new cyclopentenoid-tetrol from Eucommia ulmoides. Tetrahedron 30(23−24):4117−21

    doi: 10.1016/S0040-4020(01)97394-6

    CrossRef   Google Scholar

    [15]

    Cheng J, Zhao YY, Cui YX. 2000. Studies on Flavonoids from Leave of Eucommia ulmoides Oliv. China Journal of Chinese Materia Medica 25(5):284

    doi: 10.3321/j.issn:1001-5302.2000.05.010

    CrossRef   Google Scholar

    [16]

    Tang FR, Zhang ZL, Zuo YM, Chen LY, Luo J, et al. 2014. Chemical components of flavonoids of Eucommiae folium. Chinese Journal of Experimental Traditional Medical Formulae 20(5):90−92

    Google Scholar

    [17]

    Sun LP, Ma L, Zhang B, Xu H. 2009. Research process of flavonoids in Eucommia ulmoides. Science and Technology of Food Industry 2009(3):359−63

    Google Scholar

    [18]

    Zuo YM, Zhang ZL, Li YY, Chen LY, Liu RH, et al. 2014. Study on the chemical components of lignans of Folium eucommiae. Lishizhen Medicine and Materia Medica Research 25:1317−19

    doi: 10.3969/j.issn.1008-0805.2014.06.014

    CrossRef   Google Scholar

    [19]

    Luo LF, Wu WH, Ouyang DS, Zhou HH. 2006. Antihypertensive components and mechanisms of Eucommia ulmoides. Chinese Traditional and Herbal Drugs 37(1):150−52

    doi: 10.3321/j.issn:0253-2670.2006.01.052

    CrossRef   Google Scholar

    [20]

    Deyama T. 1983. The constituents of Eucommia ulmoides Oliv. I. Isolation of (+)-medioresinol di-O-β-D-glucopyranoside. Chemical and Pharmaceutical Bulletin 31(9):2993−97

    doi: 10.1248/cpb.31.2993

    CrossRef   Google Scholar

    [21]

    Kwan CY, Zhang WB, Deyama T, Nishibe S. 2004. Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small vessels. Naunyn-Schmiedeberg's Archives of Pharmacology 369(2):206−21

    doi: 10.1007/s00210-003-0822-4

    CrossRef   Google Scholar

    [22]

    Wu SM, Sun W, Gao YH, Ren L, Chen KM. 2021. Promoted effect of pinoresinol diglucoside on bone formation of osteoblasts in vitro culture. Journal of Chinese Medicinal Materials 33(5):9−12

    doi: 10.3969/j.issn.2095-140X.2021.05.003

    CrossRef   Google Scholar

    [23]

    Chen L, Huang X, Li X, Zhang T, Hao C, et al. 2020. Geniposide promotes the proliferation and differentiation of MC3T3-E1 and ATDC5 cells by regulation of microRNA-214. International Immunopharmacology 80:106121

    doi: 10.1016/j.intimp.2019.106121

    CrossRef   Google Scholar

    [24]

    Li Y, Zhang Y, Zhang X, Lu W, Liu X, et al. 2020. Aucubin exerts anti-osteoporotic effects by promoting osteoblast differentiation. Aging 12(3):2226−45

    doi: 10.18632/aging.102742

    CrossRef   Google Scholar

    [25]

    Kwon SH, Lee HK, Kim JA, Hong SI, Kim SY, et al. 2011. Neuroprotective effects of Eucommia ulmoides Oliv. bark on amyloid beta25-35-induced learning and memory impairments in mice. Neuroscience Letters 487(1):123−27

    doi: 10.1016/j.neulet.2010.10.042

    CrossRef   Google Scholar

    [26]

    Zhu YL, Sun MF, Jia XB, Zhang PH, Xu YD, et al. 2018. Aucubin alleviates glial cell activation and preserves dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian mice. NeuroReport 29(13):1075−83

    doi: 10.1097/WNR.0000000000001075

    CrossRef   Google Scholar

    [27]

    Chen S, Zeng X, Zong W, Wang X, Chen L, et al. 2019. Aucubin alleviates seizure activity in Li-pilocarpine-induced epileptic mice: Involvement of inhibition of neuroinflammation and regulation of neurotransmission. Neurochemical Research 44(2):472−84

    doi: 10.1007/s11064-018-2700-y

    CrossRef   Google Scholar

    [28]

    Zhang L, Ravipati AS, Koyyalamudi SR, Jeong SC, Reddy N, et al. 2013. Antifungal and anti-bacterial activities of ethanol extracts of selected traditional Chinese medicinal herbs. Asian Pacific Journal of Tropical Medicine 6(9):673−81

    doi: 10.1016/S1995-7645(13)60117-0

    CrossRef   Google Scholar

    [29]

    Wang MY, Zhu YL. 2018. Study on the bacteriostasis effects of Folium Eucommiae extracting solution on five common bacteria in vitro. Journal of Traditional Chinese Veterinary Medicine 37(2):51−52

    doi: 10.13823/j.cnki.jtcvm.2018.02.014

    CrossRef   Google Scholar

    [30]

    Sun YL, Dong JX, Wu SG. 2004. Experimental study on anti-HIV activity of Eucommia ulmoides Oliv. Journal of Preventive Medicine of Chinese People's Liberation Army 22(2):101−3

    doi: 10.3969/j.issn.1001-5248.2004.02.007

    CrossRef   Google Scholar

    [31]

    Li J, Liang X, Zhou B, Chen X, Xie P, et al. 2019. (+)-pinoresinol-O-β-D-glucopyranoside from Eucommia ulmoides Oliver and its anti-inflammatory and antiviral effects against influenza A (H1N1) virus infection. Molecular Medicine Reports 19(1):563−72

    doi: 10.3892/mmr.2018.9696

    CrossRef   Google Scholar

    [32]

    Li WY, Zhang JX, Xie XW, Shi XF. 2024. Research progress on chemical components, pharmacological activities, and modern applications of Eucommiae Folium. Natural Product Research and Development, 36(5):900−17

    doi: 10.16333/j.1001-6880.2024.5.018

    CrossRef   Google Scholar

    [33]

    Zhang WP, Zhu W, Zhang L, Fu DM, Zhang ZD, et al. 2023. Contents of main active ingredients and correlation with different ages and parts of Eucommia ulmoides Oliv. Non-wood Forest Research 38(3):46−57

    doi: 10.14067/j.cnki.1003-8981.2020.03.006

    CrossRef   Google Scholar

    [34]

    Zhong SJ, Yang X, Li J, Li YM, Li XS. 2017. Study on the total flavonoids content and antioxidant activity in different parts of Eucommiae ulmoides. China Pharmacy 28(13):1787−90

    doi: 10.6039/j.issn.1001-0408.2017.13.17

    CrossRef   Google Scholar

    [35]

    Deng SL, Yu JH, Guan L. 2007. The determination of flavonoids in different parts of Eucommia ulmoides Oliver. Biomass Chemical Engineering 41(03):37−38

    doi: 10.3969/j.issn.1673-5854.2007.03.010

    CrossRef   Google Scholar

    [36]

    Lv Q, Peng M J, Peng S, Lan WJ, Zhang CW, et al. 2012. Effects of different cultivation modes on the content of various active ingredients in leaves and bark of Eucommia ulmoides. Non-wood Forest Research 30(1):73−76

    doi: 10.3969/j.issn.1003-8981.2012.01.014

    CrossRef   Google Scholar

    [37]

    Zhang Z, Fu D, Zhang W, Zhang L, Zu Y. 2019. Simultaneous determination of 5 phenylpropanoids in Eucommia ulmoides Oliv. in different parts with different growth ages by HPLC. Food Science 40(8):186−91

    doi: 10.7506/spkx1002-6630-20180417-231

    CrossRef   Google Scholar

    [38]

    Li L, Guo Y, Zhao L, Zu Y, Gu H, et al. 2015. Enzymatic hydrolysis and simultaneous extraction for preparation of genipin from bark of Eucommia ulmoides after ultrasound, microwave pretreatment. Molecules 20(10):18717−31

    doi: 10.3390/molecules201018717

    CrossRef   Google Scholar

    [39]

    Huang S, Zhang Z, Wang Z, Chen Y, Jin X, et al. 2022. Study on difference of chlorogenic acid content in Eucommia ulmoides leaves under different harvesting time and optimization of chlorogenic acid extraction process. Feed Research 45(15):84−87

    doi: 10.13557/j.cnki.issn1002-2813.2022.15.018

    CrossRef   Google Scholar

    [40]

    He XR, Li YS, Yang F, Rao H, Chang Y, et al. 2013. The effect of different harvesting time and drying methods on the contents of chlorogenic acid in Eucommia ulmoides Oliv. leaves. Northwest Pharmaceutical Journal 28(2):130−32

    doi: 10.3969/j.issn.1004-2407.2013.02.007

    CrossRef   Google Scholar

    [41]

    Wu KX, Wu B, Peng XX, Tang ZH, Chen LW. 2019. Active constituents and Eucommia gum content of Eucommia ulmoides Oliver from multiple origins. Journal of Northeast Forestry University 47(10):40−43,74

    doi: 10.3969/j.issn.1000-5382.2019.10.009

    CrossRef   Google Scholar

    [42]

    Li Y, Wei H, Yang J, Du K, Li J, Du K, Li J, et al. 2020. High-quality de novo assembly of the Eucommia ulmoides haploid genome provides new insights into evolution and rubber biosynthesis. Horticulture Research 7:183

    doi: 10.1038/s41438-020-00406-w

    CrossRef   Google Scholar

    [43]

    Vanholme R, Demedts B, Morreel K, Ralph J, Boerjan W. 2010. Lignin biosynthesis and structure. Plant Physiology 153(3):895−905

    doi: 10.1104/pp.110.155119

    CrossRef   Google Scholar

    [44]

    Zhang SS, Zhao LQ, Xu JY, Shan CM, Wu JW. 2022. Identification of key enzyme genes involved in biosynthesis pathways of lignan and lignin in Eucommia ulmoides based on transcriptome assembly. China Journal of Chinese Materia Medica 47(14):3765−72

    doi: 10.19540/j.cnki.cjcmm.20220414.101

    CrossRef   Google Scholar

    [45]

    Kim HY, Moon BH, Lee HJ, Choi DH. 2004. Flavonol glycosides from the leaves of Eucommia ulmoides O. with glycation inhibitory activity. Journal of Ethnopharmacology 93(2):227−30

    doi: 10.1016/j.jep.2004.03.047

    CrossRef   Google Scholar

    [46]

    Li YF, Guo CJ. 2002. Metabolic research progress of quercetin. Progress in Physiological Sciences 2002(1):53−55

    doi: 10.3321/j.issn:0559-7765.2002.01.014

    CrossRef   Google Scholar

    [47]

    Zhou T, Yu Y, Xiao B, Bao L, Gao Y. 2017. Engineering of a flavonoid 3′-hydroxylase from tea plant (Camellia sinensis) for biosynthesis of B-3′,4′-dihydroxylated flavones. Acta Microbiologica Sinica 57(3):447−58

    doi: 10.13343/j.cnki.wsxb.20160330

    CrossRef   Google Scholar

    [48]

    Li TZ, Du HY, Wang L. 2014. Differential expression of related genes of flavonoids biosynthesis in Eucommia ulmoides. Non-wood Forest Research 32(1):21−26

    doi: 10.14067/j.cnki.1003-8981.2014.01.004

    CrossRef   Google Scholar

    [49]

    Li L, Liu M, Shi K, Yu Z, Zhou Y, et al. 2019. Dynamic changes in metabolite accumulation and the transcriptome during leaf growth and development in Eucommia ulmoides. International Journal of Molecular Sciences 20(16):4030

    doi: 10.3390/ijms20164030

    CrossRef   Google Scholar

    [50]

    Wu LQ, Zhu WX, Zhang YX, Fu DD, Zhang ZX. 2005. Analysis of chlorogenic acid content and extraction detection method in Eucommia ulmoides Oliv. Food Science 26:187−92

    doi: 10.3321/j.issn:1002-6630.2005.z1.048

    CrossRef   Google Scholar

    [51]

    Kundu A, Vadassery J. 2019. Chlorogenic acid-mediated chemical defence of plants against insect herbivores. Plant Biology 21(2):185−89

    doi: 10.1111/plb.12947

    CrossRef   Google Scholar

    [52]

    Franke R, Humphreys JM, Hemm MR, Denault JW, Ruegger MO, et al. 2002. The Arabidopsis REF8 gene encodes the 3-hydroxylase of phenylpropanoid metabolism. Plant Journal 30:33−45

    doi: 10.1046/j.1365-313X.2002.01266.x

    CrossRef   Google Scholar

    [53]

    Niggeweg R, Michael AJ, Martin C. 2004. Engineering plants with increased levels of the antioxidant chlorogenic acid. Nature Biotechnology 22:746−54

    doi: 10.1038/nbt966

    CrossRef   Google Scholar

    [54]

    Ye J, Han W, Deng P, Jiang Y, Liu M, et al. 2019. Comparative transcriptome analysis to identify candidate genes related to chlorogenic acid biosynthesis in Eucommia ulmoides. Trees 33(5):1373−84

    doi: 10.1007/s00468-019-01865-y

    CrossRef   Google Scholar

    [55]

    Bamba T, Murayoshi M, Gyoksen K, Nakazawa Y, Okumoto H, et al. 2010. Contribution of mevalonate and methylerythritol phosphate pathways to polyisoprenoid biosynthesis in the rubber-producing plant Eucommia ulmoides Oliver. Zeitschrift für Naturforschung C 65:363−72

    doi: 10.1515/znc-2010-5-608

    CrossRef   Google Scholar

    [56]

    Vranová E, Coman D, Gruissem W. 2012. Structure and dynamics of the isoprenoid pathway network. Molecular Plant 5:318−33

    doi: 10.1093/mp/sss015

    CrossRef   Google Scholar

    [57]

    McGarvey DJ, Croteau R. 1995. Terpenoid metabolism. The Plant Cell 7(7):1015−26

    doi: 10.2307/3870054

    CrossRef   Google Scholar

    [58]

    Chen X, Li J, Yang C, Fang X, Wang L. 2013. Biosynthesis and regulation of secondary terpenoid metabolism in plants. Scientia Sinica (Vitae) 43(12):1030−46

    doi: 10.1360/052013-307

    CrossRef   Google Scholar

    [59]

    Wang L, Wuyun TN, Ye SJ. 2013. Analysis on gene differential expression in ripe and young fruits of Eucommia ulmoides by MVA pathway. Non-wood Forest Research 31(4):45−51

    doi: 10.14067/j.cnki.1003-8981.2013.04.010

    CrossRef   Google Scholar

    [60]

    Chen PL, Wu JY, He SA. 1992. The present status and conservation strategies for Eucommia ulmoides. Journal of Plant Resources and Environment 1(4):6−11

    Google Scholar

    [61]

    Deng JY, Li JQ, Huang HW. 2006. Discovery of an originally wild tree of Eucommia ulmoides by AFLP fingerprinting. Journal of Wuhan Botanical Research 24(6):509−13

    doi: 10.3969/j.issn.2095-0837.2006.06.005

    CrossRef   Google Scholar

    [62]

    Zhou SH, Li ZQ, Li Y. 2010. Variation of plus tree opening pollinated family of Eucommia ulmoides and primary selection of seedling. Journal of Northwest Forestry University 25(1):57−60

    Google Scholar

    [63]

    Wei YC, Li ZQ, Li Y, et al. 2012. Genetic analysis of morphological trait of Eucommia ulmoides hybrid offspring. Journal of Northwest A&F University 40(8):137−43

    Google Scholar

    [64]

    Mi YN, Zhang SH, Cai Y, Liang XJ, Jiang C, et al. 2015. Genetic diversity and relationship analysis of the Eucommia ulmoides germplasm using simple sequence repeat (SSR) markers. Lishizhen Medicine and Materia Medica Research 26(10):2507−9

    Google Scholar

    [65]

    Yao X, Deng J, Huang H. 2012. Genetic diversity in Eucommia ulmoides, an endangered traditional Chinese medicinal plant. Conservation Genetics 13(6):1499−507

    doi: 10.1007/s10592-012-0393-3

    CrossRef   Google Scholar

    [66]

    Zhang BY, Zhang KJ, Wang YQ, Bai MS. 2003. The selection of fine germplasm regions and variant types of Eucommia ulmoides. Journal of Northwest Forestry University 18(4):32−34

    doi: 10.3969/j.issn.1001-7461.2003.04.010

    CrossRef   Google Scholar

    [67]

    Hu DJ. 1952. The Eucommia ulmoides in Hunan province. Plant Physiology Communications 1952(2):26−27

    Google Scholar

    [68]

    Zhu JL, Du HY, Li FD, Zhao Y, Sun Z, et al. 2014. Leaf traits and active component content in three varieties of Eucommia ulmoides. Journal of Northeast Forestry University 42(3):42−44

    doi: 10.3969/j.issn.1000-5382.2014.03.010

    CrossRef   Google Scholar

    [69]

    Du HY, Sun XY, Du LY, Sun ZQ. 2005. Variation of gutta-percha content characteristics of leaves of Eucommia ulmoides in different areas. Journal of Beijing Forestry University 27(5):103−6

    doi: 10.3321/j.issn:1000-1522.2005.05.018

    CrossRef   Google Scholar

    [70]

    Du HY, Li FD, Du LY, Xie B. 2006. Difference of samara's form characters and gutta-percha content from different producing areas associated with Eucommia ulmoides. Scientia Silvae Sinicae 42(3):35−39

    doi: 10.11707/j.1001-7488.20060307

    CrossRef   Google Scholar

    [71]

    Tang SJ, Sheng N, Lu CG, et al. 1999. The contents of chlorogenic acid and total flavonoids of Eucommia ulmoides leaves among provenances. Journal of Plant Resources and Environment 8(1):59−60

    Google Scholar

    [72]

    Tang SJ, He SA, Sheng N, Li W. 2004. The content analysis of syringaresnol diglucoside and geniposidic acid in Eucommia ulmoides leaves of different provenances. Journal of Plant Resources and Environment 13(2):58−59

    doi: 10.3969/j.issn.1674-7895.2004.02.015

    CrossRef   Google Scholar

    [73]

    Zhang BY, Zhang KJ, Zhang T, Su YQ, Dong JE, et al. 2004. Researches on the selection and breeding of superior of Qingzhong 1-4. Journal of Northwest Forestry College 19(3):18−20

    doi: 10.3969/j.issn.1001-7461.2004.03.006

    CrossRef   Google Scholar

    [74]

    Du HY, Zhang ZY, Liu BD, et al. 1994. Selection and breeding of five excellent clones of Eucommia ulmoides. Journal of Northwest Forestry University 9(4):27−31

    Google Scholar

    [75]

    Du HY, Li FD, Li FT, Fu JM, Sun ZQ, et al. 2010. An elite variety for samara use: Eucommia ulmoides 'Huazhong No. 7'. Scientia Silvae Sinicae 46(9):186

    Google Scholar

    [76]

    Du QX, Liu PF, Wang L, Du LY, Sun ZQ, et al. 2024. 'Huazhong No. 23': a new cultivar of Eucommia ulmoides. Journal of Nanjing Forestry University (Natural Sciences Edition) 48(1):257

    doi: 10.12302/j.issn.1000-2006.202204016

    CrossRef   Google Scholar

    [77]

    Zhu DY, Jiang JH, Pei DQ, et al. 1997. Plant regeneration from dry mature seed's endosperm of Eucommia ulmoides. Chinese Science Bulletin 42(5):559−560

    doi: 10.3321/j.issn:0023-074X.1997.05.032

    CrossRef   Google Scholar

    [78]

    Zhang HL, Li JH, Li ZQ. 2008. Studies on polyploidy induction in vitro of Eucommia ulmoides. Journal of Northwest Forestry University 23(1):78−81

    Google Scholar

    [79]

    Zhang HF, Guo BL, Zhang CH, Yang JX, Guo J, et al. 2008. Induction and identification of tetraploids in Eucommia ulmoides. Acta Horticulturae Sinica 35(7):1047−1052

    doi: 10.3321/j.issn:0513-353X.2008.07.016

    CrossRef   Google Scholar

    [80]

    Gao P, Lin W, Kang XY. 2004. Pollen chromosome doubling of Eucommia ulmoides induced by colchicine. Journal of Beijing Forestry University 26(4):39−42

    doi: 10.3321/j.issn:1000-1522.2004.04.008

    CrossRef   Google Scholar

    [81]

    Mao YK, Zhang PD, Shi L, et al. 2013. The optimum conditions for inducing 2n pollen chromosome doubling by high temperature in Eucommia ulmoides. Journal of Beijing Forestry University 35(1):53−58

    Google Scholar

    [82]

    Li Y, Wang Y, Wang P, Yang J, Kang X. 2016. Induction of unreduced megaspores in Eucommia ulmoides by high temperature treatment during megasporogenesis. Euphytica 212(3):515−24

    doi: 10.1007/s10681-016-1781-4

    CrossRef   Google Scholar

    [83]

    Li Y, Geng X, Song L, Kang X. 2024. Chromosome doubling of embryo sac induced by high temperature for selective breeding of triploid in Eucommia ulmoides. Molecular Plant Breeding 16(17):5743−51

    doi: 10.13271/j.mpb.016.005743

    CrossRef   Google Scholar

    [84]

    Li Y, Yang J, Song L, Qi Q, Du K, et al. 2019. Study of variation in the growth, photosynthesis, and content of secondary metabolites in Eucommia triploids. Trees 33(8):817−26

    doi: 10.1007/s00468-019-01818-5

    CrossRef   Google Scholar

  • Cite this article

    Li Y, Kang X. 2024. Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides. Medicinal Plant Biology 3: e027 doi: 10.48130/mpb-0024-0028
    Li Y, Kang X. 2024. Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides. Medicinal Plant Biology 3: e027 doi: 10.48130/mpb-0024-0028
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Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides

  • State Key Laboratory of Tree Genetics and Breeding, National Engineering Research Center of Tree Breeding and Ecological Restoration, College of Biological Sciences and Technology, Beijing Forestry University, Beijing 100083, China

  • Received: 20 July 2024
  • Revised: 23 October 2024
  • Accepted: 28 October 2024
  • Published online: 05 December 2024
Medicinal Plant Biology  3,  Article number: e027  (2024)  |  Cite this article

Abstract: Eucommia ulmoides, a tertiary relict plant species, remains the only extant representative of both the genus Eucommia and the family Eucommiaceae. With a history of more than two millennia of use in traditional Chinese medicine, its bark, leaves, and fruits harbor a diverse array of bioactive compounds, including flavonoids, iridoids, lignans, and phenylpropanoids. These compounds have various effects, such as regulating blood pressure, preventing osteoporosis, providing neuroprotection, modulating the immune system, and exhibiting antimicrobial and antiviral activities, as well as improving hypoxia tolerance and reducing lipid levels. In recent years, significant advancements have been made in the identification of bioactive components, pharmacological research, understanding the genetic basis of biosynthesis, breeding of new varieties, and the development of efficient cultivation techniques. These advancements have positioned Eucommia as a species with an extensive range of research interests. However, several challenges persist in the advanced development of Eucommia. These include insufficient research on pharmacological mechanisms, limited genetic diversity, and prolonged traditional cultivation cycles. To overcome these challenges, future research efforts should focus on breaking these bottlenecks by selecting high-yield, high-quality varieties through a combination of conventional and unconventional breeding methods. Additionally, integrating intensive cultivation techniques with comprehensive utilization strategies is crucial. Promoting the establishment of a green circular economy centered around the active ingredients of Eucommia can further enhance the economic benefits of the Eucommia industry.

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    Introduction

    • Eucommia ulmoides (E. ulmoides), a tertiary relict species belonging to the family Eucommiaceae, is a monotypic genus with a chromosome count of 2n = 2X = 34. It is a versatile economic tree species endemic to China. Its distribution is primarily concentrated in the middle and lower reaches of the Yangtze River in China[1,2]. E. ulmoides likely exhibited broad adaptability in its evolutionary history[3]. Fossil evidence indicates that primitive E. ulmoides had a widespread distribution during the Miocene epoch, spanning nearly the entire Northern Hemisphere, but became restricted to central China following the Quaternary glaciation[4]. Consequently, this species can be introduced and cultivated in numerous regions worldwide. Presently, it is cultivated extensively across a vast geographic range in China, including between latitudes 22° N and 42° N and longitudes 100° E to 121° E, encompassing a planting area exceeding 400,000 hectares. This accounts for more than 99% of the global E. ulmoides resources[5]. Furthermore, the species has been successfully introduced to countries such as the United States, the United Kingdom, France, Ukraine, Russia, Australia, Japan, and South Korea.

      E. ulmoides, a traditional and esteemed Chinese medicinal herb has a medicinal history spanning over two millennia (Fig. 1a). It was classified as a superior herb in the Han Dynasty's 'Shennong Ben Cao Jing' and is renowned for its antiaging properties[5]. Modern research has identified biologically active substances such as chlorogenic acid, aucubin, geniposidic acid, and geniposide in its bark, leaves, and fruits, which contribute to its efficacy in regulating blood pressure, preventing osteoporosis, improving neuroprotection, immune modulation, and antimicrobial and antiviral activities, enhancing hypoxia tolerance, and lowering blood lipids[1,2,5−7]. Furthermore, E. ulmoides shows promise as a temperate tree species for industrial gum production because its leaves contain 2%−3% gum (Fig. 1c), its bark contains 10%−12% gum (Fig. 1b), and its fruits contain 10%−18% gum[1,2]. The gum from E. ulmoides shares the same chemical composition as natural rubber but differs in its chemical structure, being trans-polyisoprene, which lacks elasticity. However, when modified, this compound combines the dual properties of rubber and plastic. It can be processed into sulfur-cured elastic rubber, like Hevea rubber, and possesses unique features such as low-temperature shape memory[8,9]. This finding demonstrates the extensive versatility and immense value of E. ulmoides, as every part of the plant is valuable. It shows significant potential for application and development in medicine, food, and the gum industry, as well as in materials, urban and rural landscaping, and soil and water conservation.

      Figure 1. 

      Characteristics of the E. ulmoides, bark, and leaves. (a) The morphology of the adult E. ulmoides. (b) Gums contained in the bark of E. ulmoides. (c) Gums contained in the leaf of E. ulmoides.

      Since the 1950s, because of the significant development value of E. ulmoides in pharmaceuticals and rubber production, research has increasingly focused on pharmacological effects; extraction and identification of active components; rubber and drug manufacturing; germplasm resources; seedling breeding; introduction and cultivation; genetic foundation; and selection of improved varieties[1,2]. E. ulmoides has become one of the most widely studied and highly regarded tree species globally. Building on existing research, it is crucial to address and overcome the theoretical and technical bottlenecks in the development and utilization of E. ulmoides resources. Enhancing the precision and efficiency of industrial development, reducing the production costs of rubber and pharmaceuticals, and promoting the development of a green circular economy centered on the active components of E. ulmoides are vital goals. These efforts aim to meet the significant demands of human economic development and health. This review aims to provide a comprehensive overview of recent advancements in the identification, distribution, synthesis, and genetic regulation of bioactive components in E. ulmoides. It also seeks to explore the challenges and issues associated with the industrial application of these active ingredients and to propose future research directions. Ultimately, the goal is to offer significant references for the sustainable industrial utilization of E. ulmoides.

    Bioactive components and pharmacological effects of E. ulmoides

    • Modern medical research has shown that the medicinal value of E. ulmoides is associated primarily with the rich bioactive components found in its bark, leaves, male flowers, and seeds. To date, more than 200 compounds have been isolated from various parts of E. ulmoides, with the leaves containing the greatest variety and quantity of bioactive components, followed by the male flowers, with relatively fewer in the bark and seeds. These components include mainly flavonoids, iridoids, lignans, phenylpropanoids, phenolic acids, terpenes, and steroids[5,7,10] (Table 1). The flavonoids in E. ulmoides include quercetin, rutin, astragulin, kaempferol, hyperoside, isoquercitrin, catechin, and others, most of which are flavonoids of the quercetin and kaempferol glycoside types. Present lignans are mostly glycosides, including pinoresinol, olivine, dehydrodiconiferyl alcohol, and directed lipoxyglucoside, with the major component being pinoresinol diglucoside (PDG). Present iridoids are primarily monoterpene compounds, such as geniposidic acid, aucubin, asperuloside, harparin acetate, ajugoside, eucommiol, and reptoside. Phenylpropanoids have a C6-C3 structure and are precursors to lignans and flavonoids, including chlorogenic acid, caffeic acid, isochlorogenic acids A and C, guaiacylglycerol, and cobrazin[5,7,10]. Research has shown that E. ulmoides is rich in many bioactive components with high utilization values.

      Table 1.  Key active components, main existing parts, and pharmacological effects of E. ulmoides.

      Compound name Molecular formula Molecular structural formula Main existing parts Pharmacology Ref.
      Phenolic acid monomer compounds Chlorogenic acid C16H18O9 Leaves, bark, fruit pods, male flowers Antioxidant,
      anti-inflammatory,
      anti-tumor, etc      		 [11]
      Protocatechuic acid C7H6O4 Leaves, bark, fruit pods, male flowers [12]
      Caffeic acid C9H8O4 Leaves, bark, fruit pods, male flowers [13]
      Cyclohexene ether terpenes Geniposidic acid C16H22O10 Leaves, bark, fruit pods, male flowers Anti-inflammatory, promoting wound healing, diuresis, etc. [13]
      Aucubin C15H22O9 Leaves, bark, fruit pods, male flowers [14]
      Asperuloside C18O11H22 Leaves, bark, fruit pods, male flowers [13]
      Geniposide C17H24O10 Leaves, bark, male flowers [13]
      Flavonoids Quercetin C15H10O7 Leaves, fruit pods, male flowers Antioxidant, blood lipid-lowering, anti-allergy, anti-inflammatory, antiviral, anticancer, etc.
      		 [12]
      Kaempferol C15H10O6 Leaves, fruit pods, male flowers [11,15]
      Rutin C27H30O16 Leaves, bark, fruit pods, male flowers [11]
      Astragalin C21H20O11 Leaves, male flowers [11]
      Hyperoside C21H20O12 Leaves, bark [16]
      Catechin C15H14O6 Leaves, bark, fruit pods, male flowers [17]
      Lignans Pinoresinol C20H22O6 Leaves, bark Blood pressure-lowering, neuroprotective, etc. [18]
      Olivil C20H24O7 Leaves, bark [18]
      Pinoresinol diglucoside C32H42O16 Leaves, bark, fruit pods, male flowers [13]

      Ancient Chinese medical practices and modern pharmacological studies have indicated that E. ulmoides contains several important bioactive components with various beneficial effects, including blood pressure regulation, osteoporosis prevention, neuroprotection, immune modulation, and antibacterial and antiviral properties[1,2,5,7]. Among these compounds, lignan compounds such as pinoresinol diglucoside, dehydrodiconiferyl alcohol, and pinoresinol monoglucoside; phenylpropanoid compounds such as chlorogenic acid and caffeic acid; iridoid compounds such as geniposidic acid, geniposide, and aucubin; and flavonoid compounds such as quercetin and rutin all exhibit blood pressure-regulating effects. The mechanisms involve promoting nitric oxide (NO) release and inhibiting angiotensin II, calcium (Ca2+) influx, and phosphodiesterase synthesis[19−21]. E. ulmoides compounds such as pinoresinol diglucoside, kaempferol, rutin, quercetin, and geniposidic acid can promote osteoblast formation[22,23], whereas aucubin can prevent steroid hormone-induced osteoblast apoptosis, thereby helping to prevent osteoporosis[24]. Lignans from E. ulmoides bark, geniposide, and aucubin also have neuroprotective effects, such as inhibiting acetylcholinesterase activity to protect ganglion cells from damage[25], reducing the loss of dopaminergic neurons[26], and alleviating neuroinflammatory responses[27]. These compounds are potentially beneficial in treating neurodegenerative diseases such as glaucoma, Parkinson's disease, epilepsy, and Alzheimer's disease. Additionally, extracts from E. ulmoides bark and leaves exhibit varying degrees of inhibition against fungi such as Candida albicans and bacteria such as Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium[28,29]. Compounds such as chlorogenic acid and caffeic acid from E. ulmoides have been shown to protect HIV-infected cells from pathological changes to a certain extent[30]. Furthermore, pinoresinol monoglucoside inhibits H1N1 virus[31]. In the realm of pharmacological effects, the leaves and bark of E. ulmoides exhibit similar activities, which include antioxidant, hypoglycemic, and hypotensive properties[32]. However, there may be differences in the intensity and efficacy of certain pharmacological actions between the two. For instance, the leaves of E. ulmoides are more prominent in antioxidant activity, while the effects of mature leaves are superior to those of tender and old leaves in terms of central sedation, and also superior to the bark[32]. The outcomes of modern pharmacological research have illuminated the direction for the in-depth development and utilization of E. ulmoides resources. The specific pharmacological effects of E. ulmoides fruit have not been extensively discussed in existing evidence, and future research can further explore the pharmacological effects of the fruit and its differences and connections with the leaves and bark of E. ulmoides.

    Distribution and harvesting of the bioactive components of E. ulmoides

    • The bark, leaves, male flowers, and seeds of E. ulmoides all contain bioactive components, but there are significant differences in the concentrations of these components across different tissues and organs[9,10,33−35]. In general, the leaves of E. ulmoides are rich in flavonoids, iridoids, phenolic acids, terpenoids, and steroids[32]. The male flowers primarily contain iridoids, flavonoids, and triterpenoids. Seeds are rich in iridoids, whereas bark has the highest content of lignans[4,5,8,33,36]. Flavonoids are relatively most abundant in the leaves, followed by the male flowers, with lower concentrations in the bark and seeds[8,33,34,36]. The determination of total flavonoids in E. ulmoides leaves, male flowers, bark, and seeds collected from various regions in China, such as Hanzhong in Shaanxi, Yichang in Hubei, and Changzhi in Shanxi, revealed that their average contents decreased in the following order: 9.02%, 3.02%, 1.33%, and 1.22%, respectively[34]. The measurement of the total flavonoid content of various tissues and organs at different growth stages revealed that mature leaves presented the highest total flavonoid content, which was significantly different from that of young leaves. In contrast, the flavonoid contents in branches, trunks, bark, and roots at different parts or developmental stages show little variation[35]. Phenylpropanoid components are most abundant in the leaves, followed by the fruit pods, with the lowest content in the bark[9,10,32]. For example, chlorogenic acid is present in all parts of E. ulmoides, but its content in the leaves is the highest, reaching approximately 2.5%[10,33,36,37]. Lignan components are most abundant in the bark, followed by the leaves, and are least abundant in the fruit pods. For example, the content of pinoresinol diglucoside in dried bark is approximately 0.5%, which is significantly greater than that in other parts[10,33,36,38]. Iridoid components are most abundant in the fruit pods, followed by the bark and male flowers, with relatively lower leaf content. For example, the content of geniposidic acid in the leaves of E. ulmoides is approximately 1.5%, whereas in the bark of branches, it can reach up to 6.71%[10,33,36]. The spatial and temporal distribution characteristics of bioactive components in E. ulmoides suggest that in the industrial development process of this plant, it is necessary to determine the direction of utilization of different organs and tissues and the corresponding cultivation and utilization methods according to the differences in the content of the main active components.

      Research indicates that as the age of E. ulmoides trees increases, the contents of flavonoids and phenylpropanoids in the leaves tend to decrease, whereas the content of lignans increases. Conversely, the contents of lignans and protocatechuic acid in the branch bark and trunk bark of E. ulmoides tend to increase[33]. Moreover, the active components of E. ulmoides vary depending on the harvest time. For example, the total flavonoid content in E. ulmoides leaves is highest in April and May, decreases in June and July, and then slightly increases and then stabilizes after that. Consequently, this suggests that the optimal time for harvesting leaves is April and May[35]. Notably, variations in the contents of the bioactive components of E. ulmoides can be attributed to differences in planting location, tree age, organ or tissue, developmental stage or position, and preservation and processing methods[10,33,35,39−41]. This results in different optimal harvesting times; for example, the highest average content of chlorogenic acid in E. ulmoides leaves was observed in July in Zhangjiajie, Hunan, China[39], whereas in Xi'an, the highest content was found in August and September[30]. The significant differences in the bioactive component contents and optimal harvesting times of E. ulmoides are likely due to variations in the natural environments of different planting locations[10,41].

      Additionally, there are differences in the bioactive components between leaves from current-year seedling forests and those from arboreal forests. Compared with those from arboreal forests, the leaves from current-year seedling forests contain significantly greater levels of various active components, such as total flavonoids, chlorogenic acid, geniposidic acid, aucubin, and pinoresinol diglucoside. These levels were several times greater than those of E. ulmoides leaves collected from arboreal forests at the same time, indicating substantial potential for wider application[36]. Importantly, newly emerged young leaves accumulate lower levels of bioactive components. Harvesting in a leaf-oriented tree model should be based on changes in the bioactive component contents of the leaves. This can be accomplished by selecting leaves of suitable age for batch harvesting or by performing concentrated coppicing when most leaves have matured.

    Synthesis and genetic regulation of the bioactive components of E. ulmoides

    • E. ulmoides has achieved high-quality chromosome-level genome assembly and functional annotation via a haploid approach[42]. Concurrently, studies have been conducted on the key enzymes involved in the synthesis of bioactive components such as lignans, phenylpropanoids, terpenoids, and flavonoids, as well as their genetic regulation. Lignans are the principal medicinal compounds in E. ulmoides, whereas lignin plays a role in the plant's defense against pests and diseases. Both lignans and lignin share the common precursor pineol. Research indicates that the formation of pinoresinol is a critical step in the biosynthetic pathway of lignans[43]. The dirigent protein oxidase (DIR)-encoding gene plays a critical role in the biosynthesis of lignans[44]. The transcriptome of E. ulmoides contains 58 unigenes encoding the ten key enzymes involved in the biosynthetic pathways of lignans and lignin. These unigenes encompass critical processes in the biosynthesis of lignans and lignin in E. ulmoides. The expression levels of 4-coumarate-CoA ligase (4CL), hydroxycinnamoyl-CoA (HCT), cinnamoyl CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), caffeoyl-CoA 3-O-methyltransferase (CCoAOMT), DIR, and peroxidase (POD) are greater in the stem than in the leaves, whereas PAL and C4H are expressed at higher levels in the leaves than in the stem[44].

      The primary flavonoids in E. ulmoides are quercetin and kaempferol[45]. The biosynthetic pathways of these two bioactive substances are highly similar. Initially, phenylalanine is converted into p-coumaroyl-CoA by phenylalanine ammonia-lyase (PAL) and 4-coumaroyl-CoA ligase (4CL). This process is subsequently catalyzed by chalcone synthase (CHS) to produce chalcone, which is then converted into naringenin by chalcone isomerase (CHI). Naringenin undergoes consecutive catalysis by flavanone 3-hydroxylase (F3H) and flavonoid 3'-hydroxylase (F3'H) to form dihydroquercetin, which ultimately transforms into quercetin[46]. Additionally, dihydrokaempferol can be directly converted into kaempferol by flavonol synthase (FLS)[47]. Studies have shown that there are three and four family members of CHS and E. ulmoides FLS, respectively, in E. ulmoides. In contrast, CHI and flavanone F3H are highly conserved, with only one gene identified in both the fruits and leaves of E. ulmoides[48]. The gene expression of these two enzymes shows significant tissue specificity. For example, within the CHS gene family, EuCHS1 is expressed primarily in the leaves, whereas EuCHS2 is expressed mainly in the fruits[48]. In the FLS gene family, EuFLS3 and EuFLS4 have much higher expression levels in leaves than in young fruits, whereas EuFLS1 and EuFLS2 show the opposite trend[48]. Transcription factors such as MYBs and bHLHs may play crucial regulatory roles in the flavonoid synthesis and phenylpropanoid synthesis pathways in E. ulmoides leaves[49].

      The main phenylpropanoid compound is chlorogenic acid[50]. Three biosynthetic pathways for chlorogenic acid have been identified in plants[51]. The latest genome data for E. ulmoides indicate that only two pathways are involved in the biosynthesis of chlorogenic acid[42]. One pathway involves the hydroxylation of p-coumaroylquinic acid by p-coumaroylquinic acid/shikimate 3′-hydroxylase (C3′H)[52], and the other pathway involves synthesis from caffeoyl-CoA and quinic acid catalyzed by hydroxycinnamoyl-CoA quinate hydroxycinnamoyl transferase (HQT)[53]. In the E. ulmoides genome, 23 candidate genes related to six key enzyme-encoding gene families involved in the chlorogenic acid biosynthesis pathway were identified. These genes included seven PAL genes, eight 4CL genes, two C4H genes, two C3'H genes, one HCT gene, and three HQT genes[42]. Analysis of gene expression profiles in leaves and bark revealed that the expression levels of PAL (PAL2 and PAL5), C3'H2, C4H6, HQT2, and HCT are significantly greater than those of other genes[42]. Some transcription factors (TFs) from the MYB, ZIP, ERF, and WRKY families may be involved in regulating the biosynthesis of chlorogenic acid in E. ulmoides[54].

      The biosynthetic pathway of terpenoids in plants can generally be divided into three stages: the mevalonate (MVA) pathway in the cytoplasm and the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in plastids, which synthesize the five-carbon skeleton isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP)[55,56]. DMAPP and IPP, under the catalysis of geranyl diphosphate synthase (GPS), synthesize geranyl diphosphate (GPP). GPP is then converted to farnesyl diphosphate (FPP) under the catalysis of farnesyl diphosphate synthase (FPS), and finally, geranylgeranyl diphosphate (GGPP) is synthesized under the catalysis of geranylgeranyl diphosphate synthase (GGPS)[57]. Under the action of various terpenoid synthases and modifying enzymes, structurally and functionally specific terpenoid compounds are produced[58]. In E. ulmoides, 13 genes involved in the six reactions of the MVA pathway and 11 genes involved in the seven reactions of the MEP pathway were identified. Additionally, the genes involved in the catalytic synthesis of FPP, GPP, and GGPP include three GPS genes, seven GGPS genes, and four FPS genes[42]. HMGR is the first rate-limiting enzyme in the MVA pathway and serves as a crucial regulatory point in cytoplasmic terpenoid metabolism[58]. Members of the EuHMGR gene family in the MVA pathway, along with other genes such as EuMK, EuPMK, and EuMDP, show significant differential expression in young and mature fruits of E. ulmoides[59].

    Genetic variation and breeding of superior E. ulmoides varieties

    • Currently, natural forests of E. ulmoides are extremely rare, with only a few ancient trees occasionally found in their original habitats[60,61]. Although E. ulmoides is cultivated primarily in plantations, its dioecious nature and cross-pollination, coupled with seed propagation, result in significant trait variation both within and between half-sibling and full-sibling families[62,63]. Therefore, the species still maintains relatively rich genetic diversity within its populations, with the semiwild population in Shennongjia exhibiting a relatively high level of genetic diversity[62−66]. E. ulmoides exhibits rich morphological variation, with genetic differences observed in traits such as bark, leaves, branches, and fruits, leading to the formation of unique natural types. For example, bark characteristics can be categorized into smooth-barked and rough-barked types. Leaf shape variations can be classified into types such as small leaves, long leaves, and dense leaves, among others[1,2,66−68]. Under the influence of different environmental selection pressures across its vast cultivation areas, E. ulmoides has developed various geographic provenances. These geographic provenances differ in terms of leaf and seed morphology; Eucommia rubber; and the contents of bioactive compounds, such as aucubin, chlorogenic acid, total flavonoids, geniposidic acid, and geniposide[66,69,70]. Notably, E. ulmoides from southern Shaanxi, northeastern Sichuan, northwestern Hunan, and northwestern Guizhou are considered superior provenances[66].

      Cross-pollination in E. ulmoides results in abundant genetic variation within the species, allowing significant results to be achieved by directly selecting for natural variations. Currently, a series of superior varieties, such as 'Huazhong' and 'Qinzhong', have been selected from natural populations. These varieties are characterized by fast growth and high yields of leaves, male flowers, samaras, and effective compounds[71−76], thereby promoting the improvement of E. ulmoides cultivars. Because E. ulmoides is a relict tree species that is dioecious and wind-pollinated, the superior types found in nature are themselves products of intraspecific hybridization. Elite trees bred through intensive selection from large natural populations should exhibit greater genetic gains. Consequently, the difficulty of breeding new, improved E. ulmoides varieties through simple parental hybridization is very high, making it challenging to surpass the existing selected varieties. Due to the doubling of chromosome numbers, polyploid plants often exhibit significant morphological and physiological changes, such as increased cell volume, larger and thicker leaves, and higher metabolite content. Therefore, polyploid breeding has always been a promising approach for the genetic improvement of E. ulmoides[2]. Researchers have conducted extensive studies on the doubling of chromosomes in both somatic and germ cells of this species. These studies include inducing triploidy through endosperm culture[77], treating germinating seeds and seedling growth points with colchicine solution to induce tetraploidy[78,79], and doubling pollen chromosomes[80,81]. Additionally, a series of triploid E. ulmoides plants were successfully obtained by inducing the doubling of chromosomes in female gametes through high-temperature treatment[82,83]. These triploid E. ulmoides plants often exhibit excellent characteristics, such as larger leaves, faster growth, and significantly increased contents of Eucommia rubber and medicinal components[84], highlighting the potential for the genetic improvement of E. ulmoides.

    Problems and prospects

    • The bark of E. ulmoides has been a well-established medicinal herb for centuries; however, the utilization of other plant parts has not been as extensively explored. Unlike the bark, the leaves of E. ulmoides are a renewable resource that is abundantly available. Therefore, the efficient exploitation of E. ulmoides leaves is crucial for the sustainable exploitation of this plant's resources. In 2005, the leaves of E. ulmoides were officially recognized in the Chinese Pharmacopoeia. Subsequent studies have revealed that these leaves contain a plethora of physiologically active compounds, often in higher concentrations than those present in the bark. Moreover, in terms of pharmacological efficacy, the leaves and bark of E. ulmoides have been found to possess comparable potency[41]. In 2023, the leaves of E. ulmoides were officially included in the catalog of substances recognized as both food and traditional Chinese medicinal materials by the National Health Commission and the State Administration for Market Regulation of China. This recognition has opened up significant opportunities for the research, development, and application of E. ulmoides leaves across diverse industries, including pharmaceuticals, food products, dietary supplements, animal feed additives, and chemical products.

      In reviewing current research, development, and utilization of the bioactive components of E. ulmoides, significant milestones have been achieved through collaborative endeavors of all scientific researchers and industrial developers. These advancements encompass the identification of bioactive compounds and their pharmacological properties, the genetic underpinnings of biosynthesis, the spatiotemporal distribution characteristics of these components, the implementation of efficient agricultural practices, the cultivation of new varieties, and the development of comprehensive extraction techniques. These breakthroughs have laid a foundational framework for the comprehensive development of the E. ulmoides industry, contributing to the promotion of the entire industrial chain for E. ulmoides. However, it is important to recognize that current research on the bioactive substances of E. ulmoides still faces several restrictive challenges, which hinder its development and efficient utilization. For instance, current pharmacological research is predominantly confined to ethanol or water extracts of mixed components from E. ulmoides. While these extracts have shown notable pharmacological activities in areas such as antioxidant effects, blood pressure reduction, and lipid-lowering, studies on individual components are comparatively limited, and there is a significant lack of in-depth research and understanding of the synergistic effects among the various components. Although the genome sequencing of E. ulmoides has been completed, the genetic regulatory mechanisms of most of its bioactive components are still not clearly understood, primarily due to the lack of an established system for ex vitro regeneration and genetic function validation of E. ulmoides. Research on allelic variations related to relevant traits is rare, and there is a need to enhance the supportive role of basic research in breeding and its applications. The limited size of the remaining wild populations of E. ulmoides trees restricts the effectiveness of simple crossbreeding; despite breakthroughs in polyploid breeding, these advancements still depend on a somewhat random selection of parent varieties, indicating a substantial room for improvement in seed selection. The traditional cultivation of E. ulmoides as a tree crop involves long cycles, and the mechanization of harvesting is challenging, leading to high labor costs for raw material collection. Meanwhile, the cultivation model for leafy forests is still in the early stages of exploration. The utilization of bioactive substances from E. ulmoides is rudimentary, and the benefits are minimal; a comprehensive strategy for the preparation and utilization of various types of bioactive compounds has yet to be fully developed, which represents a key challenge for future industrial applications.

      Thus, it is imperative to fully acknowledge and address the restrictive challenges hindering the development of the E. ulmoides industry. Focused efforts should be directed toward key medicinal properties and other major target traits, emphasizing efficient detection, and precise assessment of active ingredients in E. ulmoides. This approach should build upon the comprehensive collection and preservation of superior genetic resources of E. ulmoides, exploring advanced techniques for high-throughput screening and accurate evaluation of active components. Research initiatives should also delve into population genetic diversity, allelic variation patterns of key traits, regulatory networks of genes related to target traits, distinctive gene expression characteristics, and their genetic effects. Such endeavors will effectively promote the integration of conventional breeding with unconventional approaches such as chromosome doubling, genetic transformation, or gene editing, aiming to cultivate new E. ulmoides varieties characterized by high yields and elevated levels of medicinal components. Moreover, enhancing the foundational work on the isolation, purification, and pharmacology of key active compounds in E. ulmoides is crucial. This includes comprehensive research on the mechanisms of action of individual active compounds and their synergistic effects when used in combination, thereby establishing a robust basis for the development of E. ulmoides-derived biopharmaceuticals. Furthermore, there is a pressing need to enhance the foundational work related to the separation, purification, and pharmacological investigation of the key active components of E. ulmoides, particularly regarding the mechanisms of action of individual bioactive compounds. A comprehensive understanding of the synergistic effects among various active ingredients and their collective impact on human and animal physiology is equally imperative. Such efforts are essential for establishing a robust foundation for the development of biopharmaceuticals derived from E. ulmoides.

      By adopting superior varieties, ultrashort-cycle leaf forest cultivation, and mechanized harvesting, raw material costs can be significantly reduced. Additionally, the comprehensive utilization of different plant parts will help distribute raw material costs more effectively. Specifically, leaf veins and bark can be used for gum production and extraction of medicinal compounds, whereas leaf mesophyll can be utilized for pharmaceutical production or as a feed additive or health supplement. The stems can be used for manufacturing particleboard, reconstituted wood, or as substrates for edible fungi, thereby achieving multiple benefits from a single source of raw material. Resolving these issues will undoubtedly catalyze the efficient development of a green circular economy centered on E. ulmoides, with a primary focus on pharmaceutical and rubber production. This advancement will propel the E. ulmoides industry into a new phase of accelerated growth, fostering sustainable innovation and economic progress.

      Acknowledgments

      • This work was supported by the National Natural Science Foundation of China (32301620) and the Eucommia ulmoides series new varieties from Beijing Forestry University's horizontal projects.

      Author contributions

      • The authors confirm contribution to the paper as follows: writing - original draft preparation: Li Y; writing - review & editing: Kang X. Both authors reviewed the results and approved the final version of the manuscript.

      Data availability

      • Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

      Conflict of interest

      • The authors declare that they have no conflict of interest.

      Rights and permissions
      • Copyright: © 2024 by the author(s). Published by Maximum Academic Press, Fayetteville, GA. This article is an open access article distributed under Creative Commons Attribution License (CC BY 4.0), visit https://creativecommons.org/licenses/by/4.0/.
    Figure (1)  Table (1) References (84)
  • About this article
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    Li Y, Kang X. 2024. Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides. Medicinal Plant Biology 3: e027 doi: 10.48130/mpb-0024-0028
    Li Y, Kang X. 2024. Advances in research on the bioactive compounds and genetic improvement of Eucommia ulmoides. Medicinal Plant Biology 3: e027 doi: 10.48130/mpb-0024-0028
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  • Introduction
  • Bioactive components and pharmacological effects of E. ulmoides
  • Distribution and harvesting of the bioactive components of E. ulmoides
  • Synthesis and genetic regulation of the bioactive components of E. ulmoides
  • Genetic variation and breeding of superior E. ulmoides varieties
  • Problems and prospects
  • Acknowledgments
  • Author contributions
  • Data availability
  • Conflict of interest
  • Rights and permissions
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