Ophiopogon root

Ophiopogon Root (Ophiopogon japonicus): A Comprehensive Reference

1. Identity

1.1 Botanical and Pharmacopoeial Names

Ophiopogonis Radix — known in Chinese as Maidong — is the root of Ophiopogon japonicus (Thunb.) Ker-Gawl. (family Liliaceae / Asparagaceae), and is a widely recognized traditional Chinese herb listed in the Pharmacopoeia of the People's Republic of China (2015 edition). Today, O. japonicus is also recorded in the Chinese Pharmacopoeia (2020 edition), the European Pharmacopoeia (10th edition), and the Hong Kong Chinese Materia Medica Standards.

Common English names include dwarf lilyturf, mondograss, fountainplant, and monkeygrass; the Japanese names ryū-no-hige ("dragon's beard") and ja-no-hige ("snake's beard") are also used. The species is native to China, India, Japan, Nepal, and Vietnam. In French it is known as Muguet du Japon.

1.2 Botanical Description

Ophiopogon japonicus is a perennial bushy herb with small, oval or spindle-shaped roots typically found in the middle or near the ends of the root system. The small tuberous roots are light brownish-yellow and very short. It is an evergreen, sod-forming perennial with linear leaves 20–40 cm long. The flowers are white through pale lilac, borne in a short raceme. The fruit is a blue berry 5 mm in diameter. Underground, this species has large stolons with tuberous roots. The seeds are spherical and the flowers are solitary or in pairs; the flowering period is from May to August, and the fruiting period lasts from August to September.

1.3 Geographic Distribution and Cultivation

O. japonicus is a perennial evergreen herb in the lily family, mainly distributed in East, South, and South-east Asia, including China, Japan, Korea, and India. O. japonicus is mainly produced in Sichuan and Zhejiang provinces in China, where the plant is called Chuanmaidong or Zhemaidong, respectively. It is also a popular ornamental plant in East Asia.

1.4 Related Species and Adulterants

As a traditional Chinese herbal drug, this plant is subject to adulteration, with some 23 species and 3 varieties from the genera Ophiopogon and Liriope having been reported as adulterants. Historically, the dry roots of Liriope spicata var. prolifera and Liriope muscari are used as clinical alternatives to O. japonicus according to the Chinese Pharmacopoeia Commission (2020).

1.5 Common Preparations and Dosage Forms

Ophiopogon japonicus is often used in compound prescriptions, including YiQiFuMai injection, Sheng Mai Yin, and Xuanmai granule. To date, the China Food and Drug Administration (CFDA) has approved patent drugs containing O. japonicus, including Shen Mai injection/granule and Xuan Mai Gan Jie capsule/granule. Its gentle, cooling nature makes it suitable for everyday use in teas and soups, and it has a long history as both a food and a medicine in China. The root is used as a whole dried tuber in decoctions, as powdered extracts in capsules and granules, and as a purified component in injectable pharmaceutical preparations for hospital use.

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2. Traditional and Historical Use

2.1 First Documentation and Classical Sources

It is known that O. japonicus was first recorded in the Shen Nong's Herbal Classic (Shennong Bencao Jing) and has been regarded as a yin-tonifying medicine in the field of traditional Chinese medicine (TCM). As a traditional Chinese herb, O. japonicus is commonly used to improve immunity and nourish the lungs, thereby relieving cough. The first mention of O. japonicus as a medicinal herb in the Shennong Herbal Classic lists it as a top-grade medicine, and it is also documented in the subsequent series of classical texts. In the Shennong Herbal Classic, it was noted for treating Qi stagnation, abdominal discomfort, and shortness of breath. The subsequent Compendium of Materia Medica (Bencao Gangmu) further praised its ability to moisten the lungs, clear mental restlessness, and strengthen Yin.

2.2 TCM Theoretical Framework

According to TCM theory, Ophiopogonis Radix nourishes the yin, promotes body fluid production, moistens the lung, eases the mind, and clears away heart fire. The herb is used to nourish the yin, regenerate body fluid, moisten the lung, and clear away heart-fire. In addition, it is used to treat lung dryness (cough, pharyngitis, and hemoptysis) caused by yin deficiency, and emaciation-thirst caused by fever and anxiety.

Ophiopogon japonicus is valued for its versatile effects in TCM, addressing conditions caused by Yin deficiency and dryness. Its main traditional indications include: Yin Deficiency and Internal Heat (relieving dry mouth, sore throat, and thirst); Heart-Related Restlessness (calming palpitations, insomnia, and anxiety); Dry Cough (moistening the lungs to ease dry cough with minimal phlegm); Gastrointestinal Discomfort (soothing stomach pain and bloating due to Qi stagnation); and Physical Weakness (strengthening Yin to combat fatigue, shortness of breath, and emaciation).

2.3 Geographic Spread of Traditional Use

Ophiopogonis Radix (Maidong in Chinese), the root of Ophiopogon japonicus, is widely used in local medicines of China, Japan, and some south-eastern Asian countries. Ophiopogon japonicus is both a food and traditional herbal medicine in Taiwan, China, Japan, and some south-eastern Asian countries.

2.4 Classical Formulas

Ophiopogonis Radix is the main component of Mai-men-dong-tang, a traditional Chinese medicinal prescription used to treat severe dry cough in patients with pharyngitis and bronchitis. YiQiFuMai (YQFM) injection is a modern Chinese medical preparation based on a historically proven TCM formula. In China, it has been considered a supplementary therapeutic strategy for treatment of heart failure. YQFM is a concoction of concentrated plant extracts consisting of water-soluble compounds extracted from Panax ginseng, the root of Ophiopogon japonicus, and the fruit of Schisandra chinensis. Ophiopogonis Radix is listed as an edible Chinese medicine by the Chinese Ministry of Public Health because of its efficiency, high availability, and safety.

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3. Key Chemical Constituents and Active Compounds

3.1 Overview of Phytochemistry

Previous phytochemical studies have shown that O. japonicus contains steroidal saponins, homoisoflavonoids, polysaccharides, volatile oils, amino acids, and other components. The major components of O. japonicus are steroidal saponins, homoisoflavonoids, and polysaccharides, which exhibit multiple pharmacological effects.

3.2 Steroidal Saponins

Effective components include steroidal saponins, of which the aglycone parts are ruscogenin, β-sitosterol, stigmasterol, and β-sitosterol-β-D-glucoside. Key identified steroidal saponin compounds include Dwarf Lilyturf Tuber-13 (DT-13), Ophiopogon-B (OP-B), Ophiopogon-D (OP-D), Liriopesides-B (LP-B), Ruscogenin (RUS), and Ophiopogon-D′ (OP-D′).

Ophiopogonin D (OP-D) is among the most extensively studied individual constituents. OP-D is a rare C27 steroid glycoside isolated from the tuber of Ophiopogon japonicus. OP-D is identified as a white crystalline powder with a molecular formula of C₄₄H₇₀O₁₆ and a molecular weight of 855.07. It is soluble in methanol, ethanol, and dimethyl sulfoxide (DMSO), and features eight OH groups and six CH₃ groups.

DT-13 is another well-studied saponin. It is formally named ruscogenin 1-O-[β-D-glucopyranosyl-(1→2)]-[β-D-xylopyranosyl-(1→3)]-β-D-fucopyranoside. After oral administration, DT-13 shows long-term absorption, extremely slow elimination, and a bioavailability of 5.51%.

The Chinese Pharmacopoeia specifies a quality-control standard for total saponin content. Total saponins in O. japonicus are determined by UV spectrophotometry with ruscogenin (RUS) as the reference standard, and the content of total saponins should not be less than 0.12% (calculated as RUS).

3.3 Homoisoflavonoids

The root also contains methylophiopogonanone A, B; ophiopogonanone A; methylophiopogonone A, B; ophiopogonone A, B; isoophiopogonone A; desmethylisoophiopogonone B; 6-aldehydoisoophiopogonone A, B; and terpenoids such as calciombornyl sulfate and terpenoid glycoside. Homoisoflavonoids represent a structurally distinct class of phenolic secondary metabolites unique to this plant family. Homoisoflavonoids may be developed into anti-inflammatory and anti-oxidative agents to treat neurodegenerative diseases.

3.4 Polysaccharides

Ophiopogon japonicus polysaccharides (OJPs), as one of the main active ingredients, are pharmacological bioactive macromolecules mainly composed of glucose (Glc) and fructose (Fru) with molecular weight between 2.48 and 325 kDa. A key polysaccharide fraction is MDG-1, a water-soluble β-D-fructan. Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed the anti-ischemic properties of MDG-1 from O. japonicus. The sphingosine 1-phosphate (S1P) signaling pathway is involved in its cytoprotective effects.

The systemic bioavailability of orally administered polysaccharides is restricted due to their high molecular weight and structural complexity, with most exerting bioactivity via gut microbial fermentation rather than direct intestinal absorption.

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4. Established Mechanisms of Action

4.1 Cardiovascular Mechanisms

Studies have shown that O. japonicus has effects on cardiovascular diseases through various mechanisms, including antioxidation, antiarrhythmia, and microcirculation improvement. Experimental evidence has confirmed that this drug has anti-arrhythmia, inhibition of platelet aggregation, reversal of myocardial ischemia, improvement of microcirculation, and other effects.

OP-D attenuated doxorubicin-induced cardiomyocyte injury by suppressing endoplasmic reticulum stress (ERS) and relieving mitochondrial damage. Mechanically, OP-D mitigated autophagy activity by diminishing the production of reactive oxygen species (ROS). OP-D reduced diabetic myocardial injuries by regulating the dynamics of mitochondria. In type 2 diabetes mice, OP-D lowered blood lipid levels and alleviated mitochondrial dysfunction.

For the polysaccharide fraction MDG-1, a mechanistic study found that MDG-1 promotes sphingosine kinase (SPHK) activity in HMEC-1 cells and increases intracellular S1P levels.

4.2 Anti-Inflammatory Mechanisms

The possible anti-inflammatory mechanism of OP-D is related to the suppression of the NF-κB signaling pathway. It was also reported that OP-D suppresses Ang II-induced activation of pro-inflammatory cytokines (IL-6, VCAM-1, and TNF-α) and NF-κB nuclear translocation.

A homoisoflavonoid compound (SH66) mediates anti-neuroinflammatory effects via inhibition of the NLRP3 inflammasome complex and reduction of active interleukin (IL)-1β. Additionally, SH66 increased neurite length in N2a neuronal cells and the level of nerve growth factor in C6 astrocyte cells, demonstrating anti-neuroinflammatory effects by down-regulating the NLRP3 inflammasome complex.

4.3 Hypoglycemic Mechanisms

MDG-1, a polysaccharide from O. japonicus, activates the PI3K/Akt signaling pathway and improves insulin sensitivity in a diabetic KKAy mouse model. Ophiopogon japonicus oligosaccharides (OJO) significantly elevated hepatic glucokinase activity, reduced phosphoenolpyruvate carboxykinase activity, increased glucagon-like peptide-1 levels, inhibited glucagon secretion, and enhanced insulin activity. Emerging evidence indicates that OJPS modulates the composition and structural organization of the gut microbiota, thereby maintaining intestinal barrier integrity and enhancing gastrointestinal and systemic homeostasis. Moreover, OJPS and its metabolic derivatives engage in dynamic interactions with microbial communities, mediating cellular signaling cascades and endocrine regulation to elicit hypoglycemic effects.

4.4 Anticancer Mechanisms

Several mixtures and purified compounds obtained from O. japonicus have been proven to exert anticancer effects by inhibiting proliferation and inducing cell cycle arrest, apoptosis, and autophagy, as well as by inhibiting metastasis and angiogenesis both in vitro and in vivo. Emerging evidence suggests that OP-D possesses numerous pharmacological activities, including bone protection, cardiovascular protection, immune regulation, anti-cancer, anti-atherosclerosis, anti-inflammatory, and anti-NAFLD activity.

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5. Scientific Evidence by Area of Use

5.1 Cardiovascular Disease

Preclinical evidence (animal and cell studies):

The polysaccharide OJP1, extracted from the root of Ophiopogon japonicus, was investigated in a rat model of isoproterenol (ISO)-induced myocardial ischemia injury. Pretreatment with OJP1 (100, 200, and 300 mg/kg) significantly reduced ISO-induced ST-segment elevation and the heart index, attenuated the levels of marker enzymes (AST, LDH, CK, and CK-MB), significantly enhanced the activities of ATPases, enhanced the activities of SOD, GPx, and CAT in serum and myocardium, and also decreased the level of MDA. Biochemical and histopathological analysis confirmed that OJP1 alleviated myocardial injury.

Polysaccharides and steroidal saponins extracted from O. japonicus have shown significant benefits in mitigating cardiac injuries caused by various pathological conditions. Studies on O. japonicus polysaccharide (OJP1) indicate its potential to protect against cardiovascular complications in diabetes and myocardial ischemia.

Although the cardioprotective mechanisms of Ophiopogon japonicus polysaccharides (OJPS) have been extensively elucidated through in vitro studies, their therapeutic potential remains insufficiently characterized in vivo due to the predominant use of standardized animal models. This limitation highlights the necessity for establishing more sophisticated and clinically relevant cardiovascular disease models.

Clinical evidence (human studies — Shengmai/Shenmai injection):

Shengmai injection (SMI) is made from purified ginseng, Radix Ophiopogonis, and Schisandra chinensis. It has cardiotonic effects and is clinically used for the adjuvant treatment of chronic heart failure (CHF). A 2020 PRISMA-compliant systematic review and meta-analysis, published in Evidence-Based Complementary and Alternative Medicine, searched eight databases (PubMed, Embase, Cochrane Library, ClinicalTrials.gov, CNKI, Wanfang, VIP, and CBM) through September 2019, including RCTs that compared basic Western medicine treatment with SMI plus basic Western medicine. Currently available evidence indicates that SMI, as an adjuvant for basic Western medicine treatment, can improve the cardiac function of patients with CHF with good safety outcomes. Nine studies reported mild adverse events, such as gastrointestinal reactions, and no serious adverse events were reported. However, clinical studies have demonstrated protective effects of Sheng Mai San and its derivative oral and injectable formulations against anthracycline-induced cardiac dysfunction and arrhythmias; unfortunately, study design limitations — including unreported randomization, allocation concealment, and blinding — have led to low-quality evidence in previous studies. Therefore, high-quality randomized controlled trials (RCTs) are necessary to rigorously evaluate the efficacy and safety.

A prospective multicenter, randomized, double-blind, placebo-controlled trial (registered ITMCTR2024000858) is currently evaluating 212 patients with breast cancer or malignant lymphoma undergoing anthracycline-based chemotherapy, who have been diagnosed with new-onset frequent premature ventricular contractions (PVCs). Participants are being randomly assigned to receive either Sheng Mai Yin or a placebo for 8 weeks alongside standard medications. The primary outcome is the reduction rate in PVC frequency. Secondary outcomes include PVC symptom scores, TCM syndrome scores, cardiac dysfunction biomarkers, and major adverse cardiovascular events.

Strength of cardiovascular evidence: Moderate for Shengmai injection/granule as an adjunct in CHF (multiple RCTs), but the quality of the underlying individual trials is frequently low due to methodological limitations. Isolated polysaccharide and saponin data are predominantly preclinical.

5.2 Diabetes and Metabolic Disorders

Preclinical evidence:

The antidiabetic properties of oligosaccharides of Ophiopogonis japonicus (OOJ) were investigated in experimental type 2 diabetic rats. OOJ was administered orally in doses of 225 and 450 mg/kg body weight to high-fat diet and low-dose streptozotocin (STZ)-induced type 2 diabetic rats for 3 weeks. Results showed that OOJ treatment could increase body weight, decrease organ-related weights of liver and kidney, reduce fasting blood glucose level, and improve oral glucose tolerance in diabetic rats.

In a diabetic KKAy mouse model, the effects of MDG-1 (a water-soluble β-D-fructan from O. japonicus) on type 2 diabetes were examined through the PI3K/Akt pathway. MDG-1 was extracted from the tube root and purified; KKAy mice were gavaged once daily with either distilled water, MDG-1, or rosiglitazone for 8 weeks, and blood glucose levels were tested regularly.

Regarding diabetic nephropathy, results from a 12-week mouse study show that MDG-1 (300 mg/kg) significantly decreased the levels of blood glucose, triglycerides, blood urea nitrogen, and albumin, and significantly inhibited the expression of transforming growth factor-beta 1 and connective tissue growth factor. Moreover, MDG-1 could alleviate glomerular mesangial expansion and tubulointerstitial fibrosis in the diabetic mice, as confirmed by histopathological examination.

In an STZ-induced diabetic nephropathy rat model, OP-D reversed renal dysfunction evidenced by decreases in serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy. These abnormalities were reversed by OP-D treatment, indicating that OP-D might possess potential as a therapeutic agent against diabetic nephropathy via inhibiting renal inflammation and oxidative stress.

In a 4-week rat model study, OJO treatment significantly alleviated polyuria and weight loss, ameliorated insulin resistance, and improved glucose and lipid metabolism disorders in T2DM rats.

Strength of diabetes evidence: Preclinical only — multiple well-mechanized animal and cell studies across different fractions (polysaccharides, oligosaccharides, saponins). No controlled human clinical trials for diabetes as a sole endpoint for O. japonicus root alone have been identified in the available literature.

5.3 Anti-Inflammatory and Antioxidant Effects

Ophiopogon japonicus has been used as a traditional Chinese medicine to cure acute and chronic inflammation and cardiovascular diseases, including thrombotic diseases, for thousands of years. A 2017 cell-based study published in BMC Complementary and Alternative Medicine isolated and evaluated compounds from the rhizome. Few studies had previously been performed to explore the relationship between the bioactive constituents of O. japonicus and their anti-inflammatory properties, and the molecular mechanisms underlying anti-inflammatory activities remained unclear. Key active constituents of O. japonicus, including saponins and homoisoflavonoids, mitigate endothelial injury, suppress vascular smooth muscle cell (VSMC) proliferation, and prevent neutrophil effects.

In diabetic rats, OJP1 enhanced antioxidant enzyme activities (SOD, CAT, and GPx) and reduced oxidative stress markers like MDA.

Strength of anti-inflammatory evidence: Primarily in vitro and animal model data. Mechanisms are increasingly well-characterized, but controlled human trials evaluating O. japonicus extracts as anti-inflammatory agents are lacking.

5.4 Anticancer Effects

Extensive in vitro and in vivo studies have shown that O. japonicus and its active compounds exhibit potential anticancer effects in a variety of cancer cells in vitro and suppress tumor growth and metastasis without causing serious toxicity in vivo. A PRISMA-compliant systematic review published in Phytomedicine in 2023 examined the anticancer potential of O. japonicus extracts and isolated compounds. Compounds including DT-13, ophiopogonin B, and ophiopogonin D showed ability to induce cell cycle arrest, activate apoptosis and autophagy, and inhibit metastasis and angiogenesis in multiple cancer cell types in vitro, with tumor suppression observed in vivo without serious toxicity.

O. japonicus contains steroidal saponins, homoisoflavonoids, polysaccharides, volatile oils, and amino acids. However, the clinical application of steroidal saponins in cancer treatment still faces limitations, and further research and development are necessary to advance their potential in tumor therapy.

Strength of anticancer evidence: Predominantly in vitro and preclinical. No human clinical trials have been identified in the available literature that evaluate O. japonicus constituents as monotherapy cancer treatments.

5.5 Gut Microbiota and Gastrointestinal Effects

Ophiopogon japonicus has been extensively utilized as both a dietary supplement and a therapeutic agent to enhance human health and manage chronic diseases, primarily through modulation of the gut microbiota and maintenance of intestinal homeostasis. However, the systemic bioavailability of orally administered polysaccharides is restricted due to their high molecular weight and structural complexity, with most exerting bioactivity via gut microbial fermentation rather than direct intestinal absorption.

Emerging evidence indicates that OJPS modulates the composition and structural organization of the gut microbiota, thereby maintaining intestinal barrier integrity and enhancing both gastrointestinal and systemic homeostasis. Moreover, OJPS and its metabolic derivatives engage in dynamic interactions with microbial communities, mediating cellular signaling cascades and endocrine regulation to elicit hypoglycemic effects.

Strength of gut microbiota evidence: Preclinical only. Mechanistic studies in animal models and ex-vivo fermentation systems are promising, but human clinical data are not available.

5.6 Neuroprotection

Homoisoflavonoids from O. japonicus may be developed into anti-inflammatory and anti-oxidative agents to treat neurodegenerative diseases. Specific homoisoflavonoid compounds demonstrated anti-neuroinflammatory effects against LPS-activated microglia-mediated inflammatory events by down-regulating the NLRP3 inflammasome complex, and may be interesting candidates for further research and development regarding prophylactics and therapeutics for inflammation-mediated neurological complications.

Strength of neuroprotection evidence: Early-stage, primarily cell-culture experiments. No human trial data are available.

5.7 Bone Protection

The inhibition of osteoclastogenesis is associated with OP-D's antioxidative properties, which decrease reactive oxygen species (ROS) levels — a critical factor in osteoclast formation. Emerging evidence suggests OP-D possesses bone protective activity among its pharmacological activities.

Strength of bone protection evidence: Preclinical/in vitro only.

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6. Body Systems and Health Areas Associated with Ophiopogon Root

• Cardiovascular system: O. japonicus exerts cardiovascular protection among its various pharmacological activities. This includes anti-arrhythmic activity, protection against myocardial ischemia, inhibition of platelet aggregation, and improvement of microcirculation.
• Endocrine and metabolic system (diabetes): OJPs have demonstrated hypoglycemic, cardioprotective, immunomodulatory, improvement of obesity, and renal protective activity.
• Respiratory system: The herb is used to treat lung dryness, cough, pharyngitis, and hemoptysis caused by yin deficiency.
• Immune system: OP-D showed immunomodulatory activities across multiple preclinical studies.
• Gastrointestinal system: In clinical use, formulas containing Maidong are used for treating constipation, diabetes, pharyngitis, laryngitis, and other diseases.
• Nervous system: Homoisoflavonoids demonstrate neuroprotective and anti-neuroinflammatory effects in cell culture models.
• Renal system: OP-D has indicated potential as a therapeutic agent against diabetic nephropathy via inhibiting renal inflammation and oxidative stress.
• Musculoskeletal system: OP-D demonstrates preliminary anti-osteoclastogenic activity via antioxidative mechanisms in cell models.

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7. Dosage Forms and Reported Dosages

The following dosages reflect those used or referenced in peer-reviewed studies and are reported here descriptively, not as prescriptive guidance.

• Dried root decoction (traditional TCM): The 2015 Chinese Pharmacopoeia specifies the standard drug substance as the dried tuberous root of O. japonicus. Ophiopogonis Radix is listed as an edible Chinese medicine by the Chinese Ministry of Public Health. Typical decoction doses cited in toxicology testing include oral gavage doses of 3.34, 6.68, and 13.35 g/kg in mice, used for safety evaluations.
• MDG-1 polysaccharide (animal studies): KKAy mice were orally administered MDG-1 or rosiglitazone for 12 weeks. The active dose found to be significant was MDG-1 at 300 mg/kg.
• OJP1 polysaccharide (animal studies): Pretreatment with OJP1 at doses of 100, 200, and 300 mg/kg significantly reduced ISO-induced myocardial injury markers in rats.
• OOJ oligosaccharides (animal studies): OOJ was administered orally in doses of 225 and 450 mg/kg body weight for 3 weeks in type 2 diabetic rats.
• Shengmai injection (human clinical setting): Shengmai injection is made from purified ginseng, Radix Ophiopogonis, and Schisandra chinensis, and has cardiotonic effects used for the adjuvant treatment of chronic heart failure. Specific doses of SMI used in individual RCTs were not uniformly reported across the identified systematic reviews.
• Shenmai injection (human clinical setting): Shenmai injection is a widely used herbal preparation containing O. japonicus as one of two basic ingredients, used in traditional Chinese medicine for the treatment of atherosclerotic coronary heart disease and viral myocarditis.

So far, no clinical study has been reported on the sole use of O. japonicus as a single-ingredient intervention. All identified human clinical research has been conducted with multi-herb formulations in which Ophiopogon root is a component.

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8. Safety Considerations and Potential Interactions

8.1 General Safety Profile

A PRISMA-compliant review covering the genera Ophiopogon and Liriope concluded that from a toxicological perspective, Ophiopogon japonicus seems to be safe. Although O. japonicus is widely known as a functional food as well as a medicinal herb, the toxicity and safety evaluations for this plant remain insufficient. Only a few toxicity studies on O. japonicus decoction have been performed.

The genetic toxicology test for O. japonicus decoction was performed based on the mouse lymphoma assay and mouse bone marrow micronucleus test (MNT). In the MNT, the decoction at doses of 3.34, 6.68, and 13.35 g/kg (oral gavage) did not show inhibitory effects on the bone marrow of mice.

8.2 Adverse Effects of Injectable Forms

Although Radix Ginseng and Radix Ophiopogonis are considered very safe in decoctions, Shenmai injection can cause allergic reactions. In a systematic review of RCTs, nine studies reported mild adverse events associated with Shengmai injection, such as gastrointestinal reactions, and no serious adverse events were reported. It should be noted that injectable preparations represent concentrated, intravenous forms that present a categorically different risk profile from oral preparations.

8.3 Cytochrome P450 and Herb-Drug Interaction Potential

The ethanol extract of Maidong (O. japonicus) has been shown to activate the pregnane X receptor (PXR) signaling pathway and induce the cytochrome P450 3A4 (CYP3A4) reporter gene, raising concern for herb-drug interactions (HDIs) when Maidong is used in combination with prescribed drugs metabolized by CYP3A4. CYP3A4 is responsible for metabolizing a wide range of pharmaceuticals, meaning concurrent use of O. japonicus ethanol extracts with such drugs may alter their plasma concentrations; however, this finding was based on laboratory assay conditions and requires confirmation in clinical pharmacokinetic studies.

8.4 Oral Bioavailability Considerations

After oral administration, DT-13 (a key steroidal saponin) shows long-term absorption, extremely slow elimination, and a bioavailability of 5.51%. For polysaccharide fractions, systemic bioavailability of orally administered polysaccharides is restricted due to their high molecular weight and structural complexity, with most exerting bioactivity via gut microbial fermentation rather than direct intestinal absorption. These pharmacokinetic characteristics are relevant to interpreting which doses used in animal experiments are likely to be pharmacologically relevant in humans.

8.5 Quality and Adulteration Risk

As a traditional Chinese herbal drug, this plant is subject to adulteration by some 23 species and 3 varieties from the genera Ophiopogon and Liriope. Misidentification could affect both the expected efficacy profile and the safety assumptions derived from studies conducted with authenticated material.

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9. Regulatory Status and Pharmacopoeial Standards

Ophiopogon japonicus is recorded in the Chinese Pharmacopoeia (2020 edition), the European Pharmacopoeia (10th edition), and the Hong Kong Chinese Materia Medica Standards. Ophiopogonis Radix is listed as an edible Chinese medicine by the Chinese Ministry of Public Health because of its efficiency, high availability, and safety. O. japonicus is a common traditional Chinese herbal drug used as the main ingredient in many prescriptions. Modern research has verified that O. japonicus can be used either as a healthy food or a therapeutic agent for disease prevention and treatment.

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10. State of the Evidence: Summary Assessment

The main components of O. japonicus include steroidal saponins, homoisoflavonoids, and polysaccharides, which have exhibited various pharmacological activities such as cardiovascular protection, anti-inflammation, anticancer, anti-oxidation, immunomodulation, cough relief, antimicrobial, and anti-diabetes. However, research on individual TCM herbs is growing but still limited by Western clinical trial standards.

The strongest clinical evidence pertains to multi-herb injectable formulas containing O. japonicus (specifically Shengmai/Shenmai injection) used as adjuncts in chronic heart failure, with multiple RCTs supporting modest benefit. Evidence for isolated constituents — polysaccharides, saponins, oligosaccharides, and homoisoflavonoids — in diabetes, cancer, inflammation, bone protection, and neuroprotection remains predominantly preclinical (animal models and cell culture). Although O. japonicus is widely known as a functional food as well as a medicinal herb, the toxicity and safety evaluations for this plant remain insufficient. The molecular mechanisms and chemical principles of this herbal medicine should be further explored.

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