Codonopsis

Codonopsis (Codonopsis pilosula): A Comprehensive Reference

1. Identity and Natural Source

Botanical and Chemical Names

The genus Codonopsis Wall. (family Campanulaceae) comprises perennial herbs mainly distributed throughout East, Southeast, and Central Asia, with approximately 46 species, of which around 39 are found in China. The primary medicinal species is Codonopsis pilosula (Franch.) Nannf., though the Chinese Pharmacopoeia and several regional pharmacopeias recognize two additional species as official sources of the drug.

In the 2020 Chinese Pharmacopoeia, the roots of three medicinal original plants are described: C. pilosula (Franch.) Nannf., C. pilosula var. modesta (Nannf.) L. D. Shen, and C. tangshen Oliv. The dried root is the official pharmaceutical part and is known by the Chinese name Dangshen, and in Japanese as Tojin.

The botanical name derives from the plant's bell-like flowers and the hairy character of its young growing parts. The Chinese name Dangshen indicates that the plant was deemed a ginseng-like herb from the Shandang region of Shanxi Province, which had historically been a principal source of ginseng. Common English designations include bellflower root and poor man's ginseng.

C. pilosula is extensively cultivated in the northwest provinces of China, such as Gansu, Sichuan, Shaanxi, Guizhou, and Shanxi, and is mainly distributed at altitudes from 1,500 to 3,000 metres.

Botanical Description

Codonopsis produces twining stems up to 2 m long. Branches are lateral, with alternately arranged leaves and small branchlets with oppositely arranged leaves. The ovate leaves are covered with short hairs and grow up to 7.3 cm long. The plant produces singular flowers at the branch tips. The bell-shaped flower is about 2 cm long and wide, yellow-green with purple spots inside, and the fruit capsule can be up to 2.4 cm long.

Common Preparations and Dosage Forms

Codonopsis extract is frequently incorporated into health products such as tablets and capsules. Additionally, it is commonly used in dietary applications like soups, teas, and porridges to nourish qi, enrich blood, and promote overall vitality.

Some species are also used as food materials in southern China and Southeast Asia, prepared as tea, wine, soup, plaster, and porridge. Alcohol tinctures are prepared by soaking the dried root in a solvent to extract its bioactive properties. Dried root powder is also used and can be added to foods and beverages.

Sulfur fumigation and drying treatment are the most critical steps in the postharvest processing of Codonopsis radix. The sulfur fumigation process involves placing fresh medicinal materials in an enclosed space and igniting sulfur to facilitate thorough contact between the material and sulfur fumes. This treatment facilitates preservation and alters the chemical composition of the finished drug.

In November 2023, China's National Health Commission and the State Administration for Market Inspection and Administration officially included Codonopsis radix in the list of substances that are both food and traditional Chinese medicine. The State Food and Drug Administration has approved nearly 200 health foods containing Codonopsis radix for production and sale.

2. Traditional and Historical Use

China

Codonopsis did not appear in any herbals prior to the Qing Dynasty; it was first mentioned in the Bencao Congxin (by Wu Yiluo; 1751) and in the Bencao Gangmu Shiyi (by Zhao Xuemin; 1765).

It is recorded in Ben Jing Feng Yuan (Qing Dynasty) that the Shang Dang herb has the power of calming and clearing the lung. According to the New Compilation of Materia Medica (Ben Cao Cong Xin, AD 1757), it can tonify the stomach and spleen and eliminate polydipsia. This is consistent with the modern pharmacological discovery that Codonopsis radix protects the gastrointestinal tract and enhances spleen and stomach function. The Gang Mu Shi Yi (AD 1765) recorded that Codonopsis radix can cure lung deficiency and benefit lung qi.

Documented as a Traditional Chinese Medicine since the Qing Dynasty in Ben Cao Cong Xin, it has been part of the Chinese Pharmacopoeia since the 1963 edition. It is frequently blended with other TCM ingredients to formulate diverse prescriptions; for instance, Si-jun-zi Decoction is employed to alleviate symptoms of qi insufficiency in the middle-jiao, spleen, and stomach weakness, reduced appetite, and bowel irregularities. The Bu-zhong-yi-qi Decoction shows promise in relieving symptoms associated with spleen and qi deficiency, including chronic diarrhea.

In traditional Chinese medicine (TCM), Codonopsis functions to replenish qi, strengthen the spleen, tonify the lungs, and nourish blood and fluids. It is commonly combined in formula with other herbs such as Astragalus and Reishi to support chronic illness, and key indications for its use include fatigue, shortness of breath, chronic cough, palpitations, loss of appetite, loose stools, and diarrhea.

Codonopsis pilosula is frequently used as a substitute for the more costly Panax ginseng, as according to TCM principles it exhibits similar therapeutic effects. In contrast to P. ginseng root, C. pilosula root does not contain ginsenosides.

The Pharmacopoeia of the People's Republic of China describes C. pilosula as having a sweet taste and neutral properties, which influence the spleen and lung meridians. This herb has been traditionally utilized to enhance the function of the middle burner and increase qi, as well as to nourish the blood, produce body fluids, fortify the spleen, and hydrate the lungs.

Korea, Japan, and Vietnam

C. pilosula is acknowledged as the accepted species of Codonopsis radix in the Korean Herbal Pharmacopoeia and is used to treat dyspepsia, relieve fatigue, and improve the respiratory system.

In the Japanese Pharmacopoeia, both the root of C. pilosula and C. pilosula subsp. tangshen are recognized as species of Codonopsis radix and are widely used as traditional medicines and as raw materials in many OTC drugs. Codonopsis radix is frequently employed as a traditional botanical drug in Vietnam, exhibiting similar applications to its usage in China.

3. Key Constituents and Active Compounds

The root of Codonopsis pilosula is the primary medicinal part, and its chemical composition is complex, containing various biologically active substances such as alkaloids, terpenoids, flavonoids, lignins, steroids, and sugars.

To date, over 100 distinct compounds, encompassing at least 21 classes, have been identified in Codonopsis radix. Although lobetyolin is regarded as its characteristic component, evidence indicates that codonopyrrolidum A/B and tangshenoside I are also key constituents.

Polysaccharides

Chemical studies have found that the main active constituents of Codonopsis radix are polysaccharides, lignans, and polyacetylenes. Among them, Codonopsis pilosula polysaccharide (CPP) has attracted considerable attention owing to its immunomodulatory, antioxidant, anti-tumor, anti-fatigue, and prebiotic activities. The polysaccharides are a heterogeneous group of macromolecules; one study found that the monosaccharide composition of a purified CPP fraction included mannose, glucose (at approximately 97%), and arabinose.

Polyacetylenes

Compounds including lobetyol, lobetyolin, 9-(tetrahydropyran-2-yl)-nona-trans,trans-2,8-diene-4,6-diyn-1-ol, and 5-hydroxymethylfurfural (5-HMF) have been isolated from the aqueous extract of C. pilosula. Lobetyolin, a polyacetylene glycoside, is considered a characteristic marker compound for the genus and has been studied for gastroprotective and anticancer properties.

Alkaloids

Alkaloids including codonopsine and codonopsinine are among the identified nitrogen-containing secondary metabolites of C. pilosula.

Flavonoids and Terpenoids

The reported constituents of C. pilosula extracts are diverse, covering both small-molecule and complex polysaccharides, bidesmosidic triterpenoid saponins (e.g., lancemasides A–B), pyrrolidine alkaloids, xanthone derivatives (e.g., coxanthone B, swertiperenine), and polyacetylene glycosides (e.g., lobetyolin).

Active compounds identified by network pharmacology approaches include stigmasterol and luteolin, both of which have been individually studied for their pharmacological properties.

5-Hydroxymethylfurfural (5-HMF)

5-HMF is a furan derivative found in C. pilosula roots and has been studied for its potential role in anti-inflammatory and hematopoietic-supportive activities, being one of the compounds that forms upon processing and drying of the root.

4. Mechanisms of Action

Research has found that Codonopsis pilosula mainly manifests its pharmacological roles through the mechanisms of inflammation regulation, oxidative stress modulation, immunomodulation, and apoptosis regulation.

Immunomodulation

Codonopsis exerts several different effects on the immune system as a result of its polysaccharides. Polysaccharides are well understood to exert immune-moderating actions.

In a mouse study, polysaccharides from C. pilosula var. modesta (CPP) were administered orally to BALB/c mice at 50, 100, and 200 mg/kg/day for seven days following cyclophosphamide-induced immunosuppression. CPP recovered the spleen index and restored levels of IFN-γ, IL-2, IL-10, and serum IgG. In addition, it elevated ileum secretory immunoglobulin A (sIgA) and the number of intestinal Lactobacillus and acetic acid content in the cecum.

Gastrointestinal Effects

Lobetyolin, a polyacetylene compound from Codonopsis radix, has a documented protective effect on gastric mucosal damage caused by ethanol and exhibits anti-ulcer effects. Modern pharmacology has demonstrated that Codonopsis radix and its active ingredients can treat stomach diseases by ameliorating gastrointestinal motility and regulating oxidase levels.

Codonopsis pilosula extract (CPE) can reduce gastric acid and pepsin secretion, possibly by inhibiting gastrointestinal movement and propulsion. Radix Codonopsis saponin extract can offset adverse influences on the intestinal tract through withstanding 5-HT, histamine, and BaCl2, and has been used to strengthen the spleen and stomach in clinical practice.

Neuroprotective Effects

Plant polysaccharides have attracted increasing attention due to their high efficiency and low toxicity. Codonopsis pilosula polysaccharide (CPP) is an essential substance known for its antioxidant and neuroprotective effects. Research has aimed to investigate the neuroprotective effect of CPP on Aβ25-35-induced damage in PC12 cells and its underlying molecular mechanisms.

CPPs have demonstrated neuroprotection against Aβ-induced toxicity and enhanced cognitive function in Alzheimer's disease models, while lobetyolin exhibits selective anticancer effects by disrupting glutamine metabolism.

Hypoglycemic Effects

Codonopsis pilosula crude polysaccharides (CPCPs) consist of β-type pyranose and inhibit the activity of α-amylase and α-glucosidase. At a dose of 1 g/kg, CPCPs reduced diabetic symptoms including modulation of body weight and blood biochemistry levels, reduced blood sugar and lipids, and decreased oxidative damage and inflammatory factor levels in a type 2 diabetic mouse model.

Antifatigue and Anti-Hypoxia Effects

A study investigated the antifatigue and anti-hypoxia activities of different extracts from C. pilosula, including polysaccharides (POL), inulin (INU), and oligosaccharides (OLI), administered orally to mice at doses of 0.25, 0.5, and 1.0 g/kg once a day for 21 days. Antifatigue activity was assessed through a weight-loaded swimming test on day 21. The results showed that only POL treatment significantly prolonged swimming time. POL groups had the strongest hypoxia tolerance, followed by OLI and water extract groups. Liver glycogen and muscle glycogen levels were significantly increased by POL at doses of 0.5 and 1.0 g/kg, whereas blood urea nitrogen and lactic dehydrogenase levels were significantly lower than in the control group. These findings are preclinical (animal-only) and have not been confirmed in human clinical trials.

5. Scientific Evidence by Area of Use

5.1 Respiratory System — Chronic Obstructive Pulmonary Disease (COPD)

A systematic review and meta-analysis assessed the efficacy and safety of Dang shen [Codonopsis pilosula (Franch.) Nannf., root] formulae for the treatment of COPD. English and Chinese databases were searched, and 48 randomized controlled trials were included. Dang shen formulae improved lung function (forced expiratory volume in 1 second) compared with conventional pharmacotherapy (mean difference 0.22 L, 95% CI 0.13–0.31, p < 0.001, I² = 5%) and quality of life (St. George's Respiratory Questionnaire) compared with placebo.

Dang shen formulae also increased distance walked in 6 minutes when combined with conventional pharmacotherapy versus conventional pharmacotherapy alone (mean difference 51.43 m, 95% CI 30.06–72.80, p < 0.001, I² = 27%) and reduced frequency and days with COPD exacerbations.

Evidence characterization: This meta-analysis represents the strongest available clinical evidence for Codonopsis in any single indication. However, a critical limitation is that all trials used Codonopsis as part of a multi-herb formula, not as an isolated monotherapy. Attributing outcomes to Codonopsis alone is therefore not possible. Additionally, most included trials were of Chinese origin, which raises methodological concerns about blinding and outcome reporting bias.

5.2 Immune System

Research has confirmed that Codonopsis helps to restore immunity post-operatively in patients after chemotherapy. The bulk of immunological evidence, however, derives from preclinical models. CPPs have been extensively explored for multiple pharmacological activities, including immunomodulatory, antitumor, antioxidant, neuroprotective, antiviral, prebiotic, hypoglycemic, anti-inflammatory, antifatigue, gastroprotective, hepatoprotective, renoprotective, and anti-hypoxia activities.

The capacity of selenized CPPs to enhance immunomodulatory, antiviral, and antitumor activities has been positively correlated with modification. These findings are currently limited to animal and cell-based studies, and controlled human clinical trials focusing specifically on Codonopsis's immune effects are lacking.

5.3 Gastrointestinal System

This herb has been clinically shown to treat hematopoietic dysfunction, coronary heart disease, hypotension, gastric ulcer, and chronic atrophic gastritis. These clinical associations, while described in TCM literature and some observational data, are not yet backed by large-scale, well-controlled randomized trials for Codonopsis as monotherapy.

Results of serum pharmacology indicate that Codonopsis radix-containing serum can ameliorate gastritis injury and selectively inhibit the proliferation of gastric cancer cells rather than normal cells, closely related to ATP production in the relevant cells. Codonopsis radix exerted anti-gastric precancerous lesion effects by ameliorating gastritis injury, and its efficacy was closely related to regulation of the energy-metabolism pathway. This evidence is at the preclinical (animal and cell) level.

5.4 Nervous System and Cognitive Function

With the continuous development of modern pharmacology, studies have gradually revealed the critical role of Codonopsis pilosula in the fields of neuroprotection, anti-aging, antioxidant, and antitumor.

As a healthcare product, Codonopsis has been reported to improve learning and memory abilities and delay senility. The underlying evidence for cognitive benefits is predominantly from animal models (particularly using β-amyloid-induced injury paradigms) and in vitro cell studies. No adequately powered human clinical trials confirming cognitive benefits have been identified in the available literature.

5.5 Blood Glucose and Metabolic Regulation

Codonopsis's hypoglycemic action is believed to be a result of its polysaccharides and likely the synergistic effect of its other active compounds. Evidence is primarily preclinical. In type 2 diabetic mouse models, Codonopsis polysaccharides demonstrated inhibition of carbohydrate-hydrolyzing enzymes (α-amylase, α-glucosidase) and modulation of gut microbiota toward more favorable compositions. Human clinical trials investigating Codonopsis as an antidiabetic agent have not been identified in the available literature.

5.6 Hematopoiesis and Cardiovascular System

Codonopsis radix and its active substances exhibit pharmacological effects including cardiotonic action and hematopoietic enhancement.

Codonopsis pilosula has significant roles in immunity, hematopoiesis, and gastrointestinal and endocrine aspects. The hematopoietic effects have been most thoroughly studied in animal models of bone marrow suppression, where CPPs restored blood cell counts. Direct human clinical trial data on hematopoietic outcomes remain limited.

5.7 Anticancer / Antitumor Activity

The anticancer effects of Radix Codonopsis's active ingredients involve multiple systems, including the respiratory, digestive, and reproductive systems. The mechanisms of action include direct induction of tumor cell apoptosis, inhibition of tumor cell proliferation, and anti-metastatic effects.

16S rDNA sequencing results have shown that C. pilosula alkali-extracted polysaccharide (CPAP) can effectively promote the enrichment of intestinal Lactobacillus in tumor-bearing mice. It may activate T cell-mediated antitumor immune functions by regulating purine metabolism and alleviate tumor-caused inflammation by promoting neutrophil degranulation, thereby inducing apoptosis in tumor cells.

Evidence characterization: All available anticancer evidence for Codonopsis as an isolated ingredient is preclinical (cell culture and animal models). No peer-reviewed human clinical trial has established Codonopsis monotherapy as an effective cancer treatment. Its use in oncology settings in China is typically as an adjunct, embedded within multi-herb TCM formulae alongside standard oncological care.

6. Body Systems and Health Areas of Association

Reviews of the literature find that Codonopsis pilosula mainly manifests important roles in several disease areas, including the cardiovascular system, nervous system, digestive system, and immune system, and it regulates the development of many diseases primarily through the mechanisms of inflammation regulation, oxidative stress, immunomodulation, and apoptosis.

• Immune system: Modulation via polysaccharides; effects on macrophage activation, T- and B-lymphocyte stimulation, and restoration of immune suppression in animal models.
• Gastrointestinal system: Associated with strengthening the immune system, improving gastrointestinal function, alleviating gastric ulcers, enhancing appetite, and reducing blood pressure.
• Respiratory system: Tonification of the lung meridian; evidence from the COPD meta-analysis of multi-herb formulae.
• Hematopoietic / blood system: Restoration of bone-marrow-related blood parameters in animal models of suppression.
• Endocrine / metabolic system: Hypoglycemic and lipid-lowering effects in preclinical models.
• Nervous system: Neuroprotective effects demonstrated in Alzheimer's and oxidative stress cell models.
• Cardiovascular system: Cardiotonic effects and blood pressure regulation in preclinical data; clinical observations in TCM practice for coronary heart disease and hypotension.

7. Dosage Forms and Reported Dosages

Dosages reported in reviewed sources are as follows:

• Traditional/clinical TCM practice (dried root decoction): Codonopsis is possibly safe when used appropriately; doses of 6–9 grams appear to be safe based on available data.
• Antifatigue/anti-hypoxia animal study: Different extracts and fractions were orally administered to mice at doses of 0.25, 0.5, and 1.0 g/kg once a day for 21 days.
• Immunosuppression animal study: Polysaccharides (CPP) were administered at 50, 100, and 200 mg/kg/day orally for seven days following cyclophosphamide injection.
• Hypoglycemic animal study: 1 g/kg of crude polysaccharides was administered in a type 2 diabetic mouse model, reducing diabetic symptoms.
• In vitro wound healing study: Different doses of Codonopsis extract were used (20, 40, 60, 80, and 100 μg/mL), with a dose-dependent effect observed on cellular proliferation.

No large-scale, phase II/III human dose-finding clinical trials for Codonopsis as a single-ingredient supplement have been identified in the available literature. All human-relevant dosage estimates in common use derive from traditional practice and extrapolation from animal studies.

8. Safety Considerations

Pharmacopeial Safety Status

Species of the Codonopsis genus are reported with extensive pharmacological activities in the immune system, blood system, digestive system, and more, with almost no toxicity at normal doses.

Overdose / High-Dose Toxicity

Overdosage (30–60 g) can lead to toxic side effects such as throat pain, vertigo, impaired vision, spasms of the legs, loss of balance, disorientation, and loss of voice. In very high doses (over 60 g/day), additional side effects have been reported.

Codonopsis is possibly safe when used appropriately. Doses of 6–9 grams appear to be safe. However, it is possibly unsafe when used in large amounts.

Pregnancy and Lactation

There is a lack of information to support the use of Codonopsis in pregnancy and lactation. As such, its use during these periods is not supported by available safety data.

Drug Interactions

Potential herb-drug interactions have been noted in the scientific literature. One published study identified herb-drug interactions between androgenic Chinese herbal medicines, including those combined with Codonopsis, and androgen receptor antagonists in prostate cancer animal models. Additionally, given Codonopsis's immunomodulatory activity, theoretical interactions with immunosuppressant drugs (e.g., cyclosporine, tacrolimus) and anticoagulants exist, though these have not been systematically characterized in human pharmacokinetic studies.

Adulteration and Quality Concerns

Current challenges in Codonopsis research and clinical use include structural heterogeneity of polysaccharides, lack of standardization, and limited clinical evidence.

Over 100 distinct compounds across at least 21 chemical classes have been identified, which makes standardization and quality control of commercial preparations highly complex. Adulteration with cheaper congener species has been documented as a concern in the commercial supply.

Sulfur Fumigation Considerations

Sulfur fumigation and drying treatment are the most critical steps in postharvest processing of Codonopsis radix. The sulfur fumigation process involves placing fresh medicinal materials in an enclosed space and igniting sulfur to facilitate thorough contact between the material and sulfur fumes. This processing method can alter the phytochemical composition of the finished root and has been subject to regulatory scrutiny regarding residual sulfur dioxide levels in the final product.

References

• Frontiers in Pharmacology / PMC: Codonopsis radix — resource utilisation, postharvest processing, quality assessment, and polysaccharide composition (2024)
• Frontiers in Pharmacology: A systematic review of the mechanism of action and potential medicinal value of Codonopsis pilosula in diseases (2024)
• PMC: A systematic review of the mechanism of action and potential medicinal value of Codonopsis pilosula in diseases (2024)
• PMC: A Systematic Review of the Phytochemical Profile and Potential Medicinal Functions of Codonopsis pilosula in Cancer (2025)
• Frontiers in Pharmacology / PMC: Radix Codonopsis — a review of anticancer pharmacological activities (2025)
• ScienceDirect: Traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis — A review (2018)
• ScienceDirect Topics: Codonopsis pilosula — Overview
• PMC: Untargeted Metabolomics — Multiple Phytometabolites in Codonopsis pilosula (2022)
• PMC: Polysaccharides from Codonopsis pilosula Modulate Immunity and Intestinal Microbiota of Cyclophosphamide-Treated Mice (2018)
• PMC: Codonopsis pilosula Polysaccharide Improved Spleen Deficiency in Mice by Modulating Gut Microbiota and Energy-Related Metabolisms (2022)
• PMC: Restorative Effects of Inulin From Codonopsis pilosula on Intestinal Mucosal Immunity, Anti-Inflammatory Activity and Gut Microbiota of Immunosuppressed Mice (2022)
• PMC: Neuroprotective Effect of Codonopsis pilosula Polysaccharide on Aβ25-35-Induced Damage in PC12 Cells via the p38MAPK Signaling Pathway (2024)
• PubMed: Dang shen [Codonopsis pilosula] Herbal Formulae for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis (2014)
• ResearchGate: Dang Shen COPD Meta-analysis — Full Data (2014)
• RSC Food & Function: Antifatigue and antihypoxia activities of oligosaccharides and polysaccharides from Codonopsis pilosula in mice (2020)
• ScienceDirect: Effects of Codonopsis pilosula crude polysaccharides on hypoglycemia and gut microbiome in a T2DM mouse model (2023)
• PMC: Proteomics and Metabolomics — Codonopsis pilosula Ameliorates Gastric Precancerous Lesions via Energy Metabolism (2022)
• PMC: Predictive Study of Active Ingredients and Potential Targets of Codonopsis pilosula for Osteosarcoma via Network Pharmacology (2021)
• PMC: Advancements in the Investigation of Chemical Components and Pharmacological Properties of Codonopsis — A Review (2024)
• Frontiers in Pharmacology: Review of botany, ethnopharmacology, phytochemistry, pharmacological effects, pharmacokinetics and toxicity of Codonopsis radix (2023)
• Herbal Reality: Codonopsis (Codonopsis pilosula) — Benefits, Uses, Safety
• Institute for Traditional Medicine (ITM Online): Codonopsis — Medicine and Food
• ScienceDirect: Codonopsis Radix — Comprehensive review of ethnopharmacology, phytochemistry, pharmacodynamics, pharmacokinetics, toxicity and clinical applications (2025)
• PMC: Preparation, structural characteristics and immune regulatory effects of Codonopsis pilosula polysaccharides — A review (2025)