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Progress in the Research and Application of the Aerial Parts of Codonopsis

Release Date:

2021-08-12

Progress in the Research and Application of the Aerial Parts of Codonopsis

Abstract: Codonopsis pilosula is a major medicinal herb, with the root traditionally regarded as the primary medicinal part; research on its aerial parts, by contrast, has been relatively limited. Yet the aerial parts contain a diverse array of bioactive compounds and exhibit considerable potential for utilization. Despite this, their exploitation and investigation remain at an early stage, with no systematic or efficient development and application having been implemented, resulting in significant resource waste. Comprehensive utilization of the aerial parts of Codonopsis pilosula can promote the integrated use of medicinal plant resources, extend the Codonopsis industry chain, enhance its economic value and farmers’ incomes, and foster the growth of local medicinal herb industries. Therefore, research on the comprehensive utilization of the aerial parts is of great significance. This review summarizes current research and the status of comprehensive utilization of the aerial parts of Codonopsis pilosula—namely the stems, leaves, and flowers—and provides an overview of their chemical constituents, biological activities, and applications in animal husbandry and food production, with the aim of providing a reference for the integrated utilization of these aerial parts and the further expansion of the Codonopsis industry chain.

The dried roots of Codonopsis pilosula are a commonly used traditional tonic herbal medicine in China, with a history of medicinal and culinary use spanning several centuries. [1-2] Various historical works, including “Ben Cao Cong Xin,” all document the use of Codonopsis pilosula in medicinal preparations. [3] The 1963 edition of the Chinese Pharmacopoeia already included Codonopsis pilosula. [4] Its roots contain a variety of chemical constituents, including polysaccharides, sesquiterpene lactones, polyynes, and glycosides. [5] , with effects such as enhancing immunity, providing antioxidant protection, and combating fatigue. [6] In addition to its traditional use in clinical practice as a Chinese medicinal herb, Codonopsis pilosula is also widely employed in traditional veterinary medicine. [7-9] Therefore, the cultivated area of Codonopsis pilosula is extensive, and it holds high economic value. [10] Among them, Gansu is the largest native production area for Codonopsis pilosula, with a current cultivated area of 3 × 10 4 hm 2 , with annual exports of at least 700–800 tonnes [10-11] The aerial parts of Codonopsis are growing vigorously. [12] , including the stem, leaves, and flowers; in production, the primary target part for cultivation is the root. [13] Typically, the aboveground parts provide the necessary nutrients and energy for the roots’ normal growth. [14] . Beyond this, it has not been reasonably developed or utilized. Moreover, appropriately removing the aboveground parts during the cultivation of Codonopsis pilosula has a positive effect on its growth. [15] For example, appropriately pruning vines can improve the microenvironment of ventilation and light transmission in the field, thereby regulating the environmental conditions conducive to disease development and reducing the incidence and severity index of root rot; topping and flower thinning are beneficial for increasing yield and improving quality. [16-17] . The appropriate removal of the aboveground parts has already been applied on a certain scale in production. [17] However, the removed aboveground parts are often treated as waste, resulting in significant resource wastage.
Traditional Chinese medicinal resources are national strategic resources, and with the advancement of TCM science, the demand for Chinese medicinal materials and natural medicines is increasing rapidly. [18-19] Meanwhile, the cultivation and production of medicinal materials generate substantial quantities of non-medicinal parts, waste, and by-products, leading to significant resource wastage. Given their continued high scientific and economic value, the utilization of unconventional parts of Chinese medicinal materials and their by-products has emerged as a critical social and scientific issue that urgently requires exploration and resolution. [20] Research has found that the aerial parts of Codonopsis pilosula—namely the flowers, stems, and leaves—still contain a variety of chemical constituents and thus possess high utilization value. [16,21] However, research in this area is still at an early stage. Comprehensive utilization of the aerial parts of Codonopsis pilosula can enhance its economic value and product added value, thereby extending the Codonopsis industry chain to a certain extent. This approach is of great significance for increasing the income of medicinal herb farmers and for promoting the development of the local medicinal material industry and the broader regional economy. [22] This paper provides a comprehensive review of the existing research and current status of the integrated utilization of the aerial parts of Codonopsis pilosula (stems, leaves, and flowers), with the aim of offering reference for the development and application of these aerial components.

1  Chemical composition

Research on the chemical constituents of the aerial parts of Codonopsis pilosula is relatively limited, with most studies conducted domestically; Korean researchers have also carried out related work. As early as 1987, He Guoyao and others [21] A study on the chemical constituents of the stems and leaves of Codonopsis pilosula revealed that they contain many of the same chemical compounds found in the roots, with higher levels of amino acids and inorganic elements than the roots. Jiang Peifen et al. [16] Similar studies have also been conducted, yielding consistent results that demonstrate that the stems, leaves, and flowers of Codonopsis pilosula contain 17 amino acids and 22 trace elements. The total amino acid content in these aerial parts is 1.3 to 5.3 times that of the root, while the trace element content is 2.27 to 3.57 times that of the root.

Using techniques such as GC, GC-MS, and NMR, a total of 52 chemical compounds listed in Table 1 have been identified; among these, the contents of polysaccharides and codonopsis saponins in the aerial parts are no lower than those in the roots, according to Jiang Peifen et al. [16] Relatively high polysaccharide content (9.40%–22.85%) was detected in the aerial parts; Cheng Ming et al. [31] A certain amount of codonopsis alkyne glycoside was detected in the leaves, flowers, and stems of Codonopsis pilosula, at levels of 0.40, 0.22, and 0.27 mg/g, respectively. Cai Xinghang et al. [32] The aerial parts yielded a relatively high content of saponins (4.12%). In addition, bioactive compounds such as chlorogenic acid, radicamine A, lancemaside, and luteolin exhibit significant pharmacological activities and hold considerable research value. [33-37] 。

The aforementioned studies provide a scientific basis for the isolation and extraction of bioactive compounds—such as total saponins, codonopsis alkyne glycosides, and codonopsis polysaccharides—from the aerial parts of Codonopsis pilosula, thereby enabling the substitution of root material in chemical component extraction, reducing extraction costs, and conserving traditional Chinese medicinal resources.

2 Biological activity

2.1 Antioxidant

Oxidative stress can trigger a wide range of human diseases and is also a major contributing factor to aging and various pathological conditions; exogenous antioxidants can effectively eliminate or mitigate oxidative damage. [37-38] . The stems, leaves, and flowers of plants exhibit strong antioxidant activity; in recent years, numerous studies have been conducted on this topic, such as those focusing on the leaves of Dendrobium officinale. [38] , the flowers, stems, and leaves of chrysanthemums [39] , Salvia miltiorrhiza leaves [40] Moreover, it exhibits strong scavenging activity against both free radicals and reactive oxygen species. [41] The aerial parts of Codonopsis pilosula, as a natural plant material, are no exception; relevant studies on their free-radical-scavenging activity are shown in Table 2. Yang et al. [22] The antioxidant activities of aqueous and alcoholic extracts of Codonopsis pilosula leaves were investigated and compared with those of the roots. At a mass concentration of 200 μg/mL, the aqueous extract exhibited a DPPH radical scavenging rate of 92.24% and an ABTS radical scavenging rate of 99.21%, demonstrating strong reducing ability toward ferric ions; moreover, at concentrations above 1.5 mg/mL, its antioxidant activity was comparable to that of vitamin C.

Notably, the antioxidant activity of the aerial parts is significantly higher than that of the roots. Antioxidant activity is generally associated with higher levels of polyphenols, flavonoids, and saponins in the samples; thus, the antioxidant activity of Codonopsis pilosula stems and leaves may be closely linked to their saponin content. [38,40-42] , and may also be related to polysaccharides. Zou et al. [43] Two pectin polysaccharides were obtained by ion-exchange chromatography and exhibited notable antioxidant activity by modulating the metabolism of intestinal epithelial cells, thereby influencing the body’s antioxidant defense system and protecting intestinal cells from oxidative damage and suppression of cellular viability induced by oxidative stress. This potent antioxidant activity represents a significant advantage for the comprehensive utilization of the aerial parts of Codonopsis pilosula, suggesting that they could be developed as antioxidants for applications in various fields, including cosmetics, health supplements, and food products.

2.2 Antibacterial

In general, saponins, flavonoids, and polysaccharides exhibit certain antibacterial activity. [19,42-43] The aerial parts of Codonopsis pilosula are rich in total flavonoids, polysaccharides, and saponins. [47] Studies have found that the methanol, water, and ethanol extracts of Codonopsis pilosula leaves exhibit a certain inhibitory effect on common bacteria, including foodborne pathogens such as Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. [22,41] , see Table 2. Bhardwaj et al. [41] The inhibitory effects of Codonopsis pilosula leaf extract on bacteria, molds, and yeasts were investigated. Moreover, these microbial strains are associated with common foodborne illnesses and food spoilage; therefore, extracts from the aerial parts of Codonopsis pilosula hold promising potential for antibacterial applications, such as the suppression of foodborne pathogens and spoilage microorganisms.

2.3 Immune regulatory function

Codonopsis polysaccharides exhibit potent immunomodulatory effects in both humans and animals. [48-49] It promotes the development and protects immune organs, activates the proliferation of macrophages and lymphocytes, elevates systemic antibody levels, and stimulates immune cells to secrete a variety of cytokines. [49] Moreover, the stems, leaves, and flowers of Codonopsis pilosula exhibit relatively high polysaccharide contents, with leaf contents reaching 0.42–0.49 mg/g, stem contents reaching 0.28–0.34 mg/g, and flower contents reaching 0.20–0.26 mg/g. [21,31] , see Table 2. Wu Zhiyong et al. [44] It was found that the addition of Codonopsis stem-and-leaf astragalus powder to chicken feed can, both individually and in synergy with polyhydroxyalkanoates, significantly stimulate T-lymphocyte proliferation and enhance antibody titers. Immunity is essential for human health and the normal growth and development of animals; the aerial parts of Codonopsis possess certain immunomodulatory effects, making their immunoregulatory functions worthy of further investigation. In particular, research on natural plant-based immunomodulation has the potential to appropriately reduce antibiotic usage, thereby holding significant scientific and practical importance.

2.4  Lipid regulation

Xie Min et al. [23] Eight lipid-regulating bioactive compounds were isolated from the stems and leaves of Codonopsis pilosula. These compounds exhibit inhibitory activity against pancreatic lipase, with inhibition rates ranging from 15% to 31%. Pancreatic lipase plays a crucial role in lipid metabolism; therefore, its inhibition can reduce dietary fat absorption. Although no in vivo studies related to this mechanism have been reported yet, many natural plant extracts are known to possess potent lipid-regulating properties. Furthermore, other lipid-regulating compounds, such as phytic acid, have also been detected in the stems and leaves of Codonopsis pilosula. [27,46] , as shown in Table 2. Therefore, the aerial parts of Codonopsis pilosula may hold certain research and application value in lipid regulation.

3 Toxicity Study

He Guoyao et al. [50] A study was conducted on the acute toxicity of Codonopsis pilosula stems and leaves in mice, and the results indicated that these plant parts did not elicit any significant toxic effects on hepatic and renal tissues or on cellular proliferation; moreover, body weight in the test animals increased. A chronic toxicity study was then carried out using roosters, which revealed no notable impacts on blood biochemical parameters. Neither gross anatomical examination nor electron microscopy disclosed any abnormalities. Therefore, the toxicity of Codonopsis pilosula stems and leaves is minimal, with a wide safety margin, thereby providing a scientific basis for the development and utilization of these plant resources. Tian Kun et al. [51] Acute, subacute, and cumulative toxicity studies were conducted on Codonopsis pilosula pollen. Based on these studies, a dose of 25 g/kg was determined to be the safe dosage, with a safety factor of 100. Within this dosage range, Codonopsis pilosula pollen is safe, non-toxic, and does not exhibit chronic cumulative toxicity. Therefore, the stems, leaves, and flowers of Codonopsis pilosula exhibit very low toxicity and high safety, making them suitable as a basis and reference for research in other fields—particularly providing a scientific rationale for the feasibility of their development and utilization in the food industry and animal husbandry.

4 Applications in Animal Husbandry

The stems and leaves of Codonopsis pilosula, as waste resources generated during its cultivation, are low-cost. Their application in animal husbandry can significantly reduce production costs while, to a certain extent, enhancing growth performance and feed utilization efficiency, thereby improving economic returns and demonstrating promising prospects for wider adoption in the livestock industry. The specific applications in animal husbandry are summarized in Table 3.

Notably, the antioxidant activity of the aerial parts is significantly higher than that of the roots. Antioxidant activity is generally associated with higher levels of polyphenols, flavonoids, and saponins in the samples; thus, the antioxidant activity of Codonopsis pilosula stems and leaves may be closely linked to their saponin content. [38,40-42] , and may also be related to polysaccharides. Zou et al. [43] Two pectin polysaccharides were obtained by ion-exchange chromatography and exhibited notable antioxidant activity by modulating the metabolism of intestinal epithelial cells, thereby influencing the body’s antioxidant defense system and protecting intestinal cells from oxidative damage and suppression of cellular viability induced by oxidative stress. This potent antioxidant activity represents a significant advantage for the comprehensive utilization of the aerial parts of Codonopsis pilosula, suggesting that they could be developed as antioxidants for applications in various fields, including cosmetics, health supplements, and food products.

2.2 Antibacterial

In general, saponins, flavonoids, and polysaccharides exhibit certain antibacterial activity. [19,42-43] The aerial parts of Codonopsis pilosula are rich in total flavonoids, polysaccharides, and saponins. [47] Studies have found that the methanol, water, and ethanol extracts of Codonopsis pilosula leaves exhibit a certain inhibitory effect on common bacteria, including foodborne pathogens such as Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. [22,41] , see Table 2. Bhardwaj et al. [41] The inhibitory effects of Codonopsis pilosula leaf extract on bacteria, molds, and yeasts were investigated. Moreover, these microbial strains are associated with common foodborne illnesses and food spoilage; therefore, extracts from the aerial parts of Codonopsis pilosula hold promising potential for antibacterial applications, such as the suppression of foodborne pathogens and spoilage microorganisms.

2.3 Immune regulatory function

Codonopsis polysaccharides exhibit potent immunomodulatory effects in both humans and animals. [48-49] It promotes the development and protects immune organs, activates the proliferation of macrophages and lymphocytes, elevates systemic antibody levels, and stimulates immune cells to secrete a variety of cytokines. [49] Moreover, the stems, leaves, and flowers of Codonopsis pilosula exhibit relatively high polysaccharide contents, with leaf contents reaching 0.42–0.49 mg/g, stem contents reaching 0.28–0.34 mg/g, and flower contents reaching 0.20–0.26 mg/g. [21,31] , see Table 2. Wu Zhiyong et al. [44] It was found that the addition of Codonopsis stem-and-leaf astragalus powder to chicken feed can, both individually and in synergy with polyhydroxyalkanoates, significantly stimulate T-lymphocyte proliferation and enhance antibody titers. Immunity is essential for human health and the normal growth and development of animals; the aerial parts of Codonopsis possess certain immunomodulatory effects, making their immunoregulatory functions worthy of further investigation. In particular, research on natural plant-based immunomodulation has the potential to appropriately reduce antibiotic usage, thereby holding significant scientific and practical importance.

2.4  Lipid regulation

Xie Min et al. [23] Eight lipid-regulating bioactive compounds were isolated from the stems and leaves of Codonopsis pilosula. These compounds exhibit inhibitory activity against pancreatic lipase, with inhibition rates ranging from 15% to 31%. Pancreatic lipase plays a crucial role in lipid metabolism; therefore, its inhibition can reduce dietary fat absorption. Although no in vivo studies related to this mechanism have been reported yet, many natural plant extracts are known to possess potent lipid-regulating properties. Furthermore, other lipid-regulating compounds, such as phytic acid, have also been detected in the stems and leaves of Codonopsis pilosula. [27,46] , as shown in Table 2. Therefore, the aerial parts of Codonopsis pilosula may hold certain research and application value in lipid regulation.

3 Toxicity Study

He Guoyao et al. [50] A study was conducted on the acute toxicity of Codonopsis pilosula stems and leaves in mice, and the results indicated that these plant parts did not elicit any significant toxic effects on hepatic and renal tissues or on cellular proliferation; moreover, body weight in the test animals increased. A chronic toxicity study was then carried out using roosters, which revealed no notable impacts on blood biochemical parameters. Neither gross anatomical examination nor electron microscopy disclosed any abnormalities. Therefore, the toxicity of Codonopsis pilosula stems and leaves is minimal, with a wide safety margin, thereby providing a scientific basis for the development and utilization of these plant resources. Tian Kun et al. [51] Acute, subacute, and cumulative toxicity studies were conducted on Codonopsis pilosula pollen. Based on these studies, a dose of 25 g/kg was determined to be the safe dosage, with a safety factor of 100. Within this dosage range, Codonopsis pilosula pollen is safe, non-toxic, and does not exhibit chronic cumulative toxicity. Therefore, the stems, leaves, and flowers of Codonopsis pilosula exhibit very low toxicity and high safety, making them suitable as a basis and reference for research in other fields—particularly providing a scientific rationale for the feasibility of their development and utilization in the food industry and animal husbandry.

4 Applications in Animal Husbandry

The stems and leaves of Codonopsis pilosula, as waste resources generated during its cultivation, are low-cost. Their application in animal husbandry can significantly reduce production costs while, to a certain extent, enhancing growth performance and feed utilization efficiency, thereby improving economic returns and demonstrating promising prospects for wider adoption in the livestock industry. The specific applications in animal husbandry are summarized in Table 3.

Image

Non-traditional parts of Chinese medicinal herbs, owing to their rich content of root-like bioactive compounds, are increasingly being studied and applied in health supplements and food products. [72-73] For example, research on the development and utilization of eucommia leaves and flowers involves processing eucommia leaves into eucommia leaf tea. [74-75] ; Wei Yuanyuan [76] and Zhu Lirong, among others [77] The processing technology and antioxidant activity of eucommia male flower tea were investigated. Currently, eucommia leaf tea and eucommia male flower tea are already on the market, and eucommia leaves have been included in the Catalogue of Medicinal and Food Homology, indicating promising economic value and development prospects. [78-79] Research and development on eucommia leaves and flowers provide valuable reference for the future development of codonopsis stems, leaves, and flowers. Accordingly, the comprehensive utilization of the aerial parts of codonopsis holds significant potential for integration with the food industry, offering substantial economic development prospects and a promising outlook for future growth.

6 Summary and Outlook

With the increasing demand, wild medicinal resources of traditional Chinese medicine are currently declining rapidly, and non-traditional medicinal parts of major medicinal materials cultivated in agricultural settings are often discarded during the cultivation process, leading to significant resource waste. The comprehensive utilization of non-medicinal parts of TCM materials is still at an early stage and has become a research hotspot. Codonopsis pilosula, as an important medicinal plant, has aboveground parts with high utilization value; however, to date, there has been no rational development or utilization of these parts. To promote the rational use of resources, extend the industrial chain of Codonopsis pilosula, enhance its economic value, increase the income of medicinal herb farmers, and accelerate the development of local medicinal material industries as pillar sectors, this paper reviews the existing research and current status of the comprehensive utilization of the aboveground parts of Codonopsis pilosula (stems, leaves, and flowers), with the aim of providing a reference for related research and applications. The results indicate that the aboveground parts of Codonopsis pilosula have considerable development potential, and the studies conducted so far have mainly focused on the detection and isolation of their chemical constituents, biological activities, and applications in animal husbandry and food. Overall, research on these parts started relatively late, and their development and utilization remain at an early stage, although He Guoyao et al. [21] Research was initiated as early as 1987, but to this day its development and utilization remain in the exploratory stage.

The aerial parts of Codonopsis pilosula contain a variety of natural phytochemicals that exhibit potent antioxidant activity and immunomodulatory effects, among other important bioactivities. In animal husbandry, these aerial parts can enhance feed utilization, improve production and growth performance, and elevate the quality of livestock products. Consequently, they hold great promise for application and development across multiple industries and sectors, with a generally optimistic outlook and particularly high economic value. It is recommended that comprehensive utilization of the aerial parts of Codonopsis pilosula be pursued in the following areas: (1) incorporation into animal feed, either as a standalone feed ingredient or as a component added to feed at specific inclusion levels; (2) formulation into animal growth regulators, such as immune-enhancing agents; (3) development into food-grade antioxidants or preservatives, or integration with the cosmetics industry to create products with antioxidant and anti-aging properties; and (4) use as a raw material for the isolation and extraction of bioactive compounds, thereby substituting for the root of Codonopsis pilosula—for example, for the extraction of codonopsis polysaccharides, codonopsis alkyne glycosides, saponins, luteolin, and other bioactive constituents—thus reducing production costs and promoting the rational utilization of traditional Chinese medicinal resources.

 

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