Semiaquilegia (Semiaquilegia adoxoides): A Comprehensive Reference
1. Botanical Identity and Nomenclature
1.1 Taxonomy and Classification
Semiaquilegia is a genus of flowering plants of the family Ranunculaceae, native to eastern Asia. The Japanese botanist Tomitaro Makino proposed the establishment of Semiaquilegia as a genus in 1902. Most authorities generally hold that there is only one species in the genus, Semiaquilegia adoxoides, though other species have been proposed as members. The Royal Botanic Gardens, Kew's Plants of the World Online accepts four species of Semiaquilegia.
The full taxonomic hierarchy, as documented in major biodiversity registries, is as follows:
- Kingdom: Plantae; Phylum: Tracheophyta; Class: Magnoliopsida; Order: Ranunculales; Family: Ranunculaceae; Genus: Semiaquilegia Makino.
Semiaquilegia is currently included in the tribe Isopyreae and is widely recognised as closely related to Aquilegia L. based on petal evolution, geographical affinities, and molecular data. Recent molecular analyses showed that Semiaquilegia, Urophysa Ulbrich, and Aquilegia form a monophyletic group, with Semiaquilegia as sister to Aquilegia.
Makino assessed the characteristics of the genus as approximating the appearance of plants in the genus Aquilegia, but with several distinctions. Among the features Makino identified were the absence of nectar spurs, the presence of fewer than 15 stamens, and possession of inner stamens that look like flattened staminodes. They are similar to Aquilegia but have spurless flowers which are swollen at the base.
1.2 The Primary Medicinal Species: Semiaquilegia adoxoides
Semiaquilegia adoxoides is a species of perennial flowering plant in the family Ranunculaceae. The species is native to Japan, Korea, and China, and is now often considered the sole member of the genus Semiaquilegia; it bears similarities to members of the genus Aquilegia. S. adoxoides is native to China, Korea, and Japan and has an introduced population on Taiwan.
The spurless columbine (Semiaquilegia adoxoides (DC.) Makino), also called Tian Kui, is a small herbaceous perennial in the Ranunculaceae family.
1.3 Common Names
- Chinese (Mandarin): Tiankuizi (天葵子) or Tian Kui — the dried root is the principal medicinal part referred to by these names.
- English: Spurless columbine; muskroot semiaquilegia.
- Pharmacopoeial name: Semiaquilegiae Radix — the name used in the Chinese Pharmacopoeia for the dried root tuber.
This medicinal plant is listed as an essential species in the Chinese Pharmacopoeia.
1.4 Morphology and Habitat
The genus Semiaquilegia comprises perennial herbaceous plants of the Ranunculaceae family. The plants possess tuberous roots. The arrangement of the leaves is basal (protruding from the stem's base) and cauline (attached to the aerial stem).
S. adoxoides can grow to about 40 cm (16 in) tall. The plant produces flowers that are usually white with purple tinging. Blooming occurs in March and April. Its tuberous roots can be 1 cm to 2 cm long and 3 mm to 6 mm in diameter.
Semiaquilegia can be easily distinguished from other genera of the Ranunculaceae by its actinomorphic flowers, distinct petals, and free carpels.
1.5 The Medicinal Part and Pharmacopoeial Status
Semiaquilegiae Radix is the dried root tuber of Semiaquilegia adoxoides (DC.) Makino (Ranunculaceae), commonly known as Tiankuizi in China. It is harvested from the wild for local use as a medicine. The tubers are described in reference literature as depurative, diuretic, and febrifuge.
2. Traditional and Historical Use
2.1 Traditional Chinese Medicine (TCM)
The dry root of Semiaquilegia adoxoides, known as Tiankuizi in traditional Chinese medicine (TCM), has been a recognized medicinal herb within the TCM system. The dry roots of this plant, called Tiankuizi in traditional Chinese medicine, have been used for their anti-inflammatory, anti-neoplastic, and antibacterial activities, and for the treatment of snakebite in folk medicine.
The tuberous root of Semiaquilegia adoxoides is used in medicine, with effects such as clearing heat and detoxifying, reducing swelling and relieving pain, and promoting diuresis. It is used to treat mastitis, tonsillitis, abscesses, scrofula, difficulty in urination, and other conditions.
As a traditional medicinal plant, S. adoxoides is often used against carbuncles, furuncles, swelling, breast carbuncles, scrofula, and snakebite; the extract from the underground stem is also cited as helpful for the prevention of cancer.
According to documentation in ancient China, the powders or aqueous extractions of S. Makino have been widely used in the treatment of furuncle swelling, tonsillitis, and mammary abscess, which are often associated with S. aureus and E. coli.
2.2 Ethnic and Folk Medicine
Semiaquilegia adoxoides (DC.) Makino (Ranunculaceae), a folk medicine of the Hmong (an ethnic group of China), has been traditionally used to treat cataract; however, the underlying molecular mechanism was yet to be uncovered at the time of that study.
It is described in traditional sources as slightly toxic and able to treat conditions such as boils and sores, mastitis, tonsillitis, lymph node tuberculosis, and traumatic injuries. The tuberous root can also be used as a botanical pesticide.
2.3 Traditional Preparation Forms
In TCM practice, the primary preparation described in the literature is the dried root tuber (Semiaquilegiae Radix). Preparations documented in the scientific literature include:
- Aqueous decoction: It is recorded that its water extract can be used to treat acute diseases caused by bacterial infections.
- Powdered form: Traditional records describe powdered preparations used for similar acute infectious conditions.
- Use in compound decoctions: Semiaquilegia adoxoides (Tian Kui Zi) is employed at 10 g as a component in classical compound decoctions such as Wuwei Xiaodu Drink; the herbal materials are typically subjected to double decoction with eight times the volume of water for 1 hour, after which the extracts are combined, filtered, and concentrated.
3. Key Chemical Constituents and Active Compounds
Thirty compounds had been reported from S. adoxoides in the literature at the time of one systematic review, including six cyano-compounds, three alkaloids, three benzoic acid derivatives, three benzofuranones, three diterpenes, three steroids, three fatty acids, two simple benzene derivatives, one nitro-compound, one flavonoid, one amide, and one furan.
A 2025 UHPLC-Q-TOF–MS/MS study identified an additional catalogue of constituents. From Semiaquilegiae Radix, 19 active compounds were identified, of which 18 showed activity against inflammation-related targets.
3.1 Kaurane-Type Diterpenoids
The kaurane-type diterpenoids are among the most pharmacologically significant compound class identified in S. adoxoides.
Two new ent-kaurane-type diterpenoids, E-semiaquilegin (1) and Z-semiaquilegin (2), together with eight known compounds, were isolated from the dried roots of Semiaquilegia adoxoides (DC.) Makino. The structures of compounds 1 and 2 were elucidated mainly by 2D NMR techniques including 1H–1H COSY, HSQC, HMBC, NOESY as 16α-hydroxy-ent-kaurane-17,20-di-(3,4-dihydroxy-E-cinnamoyl) ester and its (Z)-isomer.
Semiaquilegin A is a natural kaurane-type diterpenoid ester isolated from the roots of Semiaquilegia adoxoides (DC.) Makino, which exhibits antiproliferative activity against a broad spectrum of cancer cell lines with EC50 values ranging from 4.36 μM to 10.88 μM.
The roots of Semiaquilegia adoxoides (Ranunculaceae) are used in Chinese traditional medicine for the treatment of inflammation.
3.2 Alkaloids
The isolation of griffonilide (1), lithospermoside (2), and magnoflorine (3) from the roots of Semiaquilegia adoxoides has been reported.
A new alkaloid, 1,2,3,4-tetrahydro-6-hydroxy-1-[(3,4-dihydroxyphenyl)methyl]-7-methoxy-2,2-dimethyl-isoquinolinium, named Semiaquilegine A (1), and a new ester, 3-(4′-hydroxyphenyl)-2-propenoic acid (4′′-carboxyl)-phenyl ester (2), along with four cyano-containing compounds and eleven known compounds, were isolated from the roots of Semiaquilegia adoxoides. The presence of cyano-containing compounds is very rare in plants, and their identification in this plant is of particular scientific note.
Magnoflorine, an aporphine-type quaternary alkaloid, is a notable constituent. Magnoflorine, also named thalictrine and escholine, is a well-known alkaloid that has an aporphine configuration; its molecular formula is C20H24NO4+. The results of pharmacological investigations indicate that magnoflorine possesses a wide spectrum of pharmacological properties, including anti-diabetic, anti-inflammatory, neuropsychopharmacological, immunomodulatory, hypotensive, antioxidant, and antifungal activities.
3.3 Phenolic Compounds and Benzoic Acid Derivatives
Through bioassay-guided fractionation, thirteen compounds were isolated from the dry root of Semiaquilegia adoxoides; among these, four benzoic acid derivatives, one 4,6-dimethoxy-5-methyl-2H-pyran-2-one, and one 1,2,3-propanetriol were found for the first time in S. adoxoides.
Vanillic acid, another important component of Semiaquilegiae Radix, possesses both anti-inflammatory and antioxidant properties, exerting potent inhibitory effects against NF-κB, Toll-like receptors (TLRs), and the Janus kinase (JAK)/signal transducer and activator of transcription pathways.
3.4 Polysaccharides
The polysaccharide of Semiaquilegia adoxoides (SMP) was characterized using FT-IR and HPLC methods to determine its basic chemical structure and monosaccharide compositions, and its antioxidant capacity was analyzed by monitoring both the scavenging rate of DPPH and ABTS free radical. Results showed that SMP was a furanose which was mainly composed of glucose (60.3%) and had certain antioxidant activities.
3.5 Additional Identified Compound Classes
- Steroids (three identified)
- Benzofuranones (three identified)
- Fatty acids (three identified)
- A nitro-compound and a flavonoid
These classes are documented in the bioassay-guided fractionation literature cited above, though the pharmacological activity of each individual compound has not yet been fully characterized in all cases.
4. Established and Proposed Mechanisms of Action
4.1 Anti-Inflammatory Mechanisms
4-Hydroxybenzoic acid and 3,4-dihydroxybenzoic acid isolated from S. adoxoides showed selective inhibition against elastase release and superoxide anion generation, with IC50 values of 3.20 and 6.21 μg/mL, respectively. Compound 1 (4-hydroxybenzoic acid) had 7-fold better activity than the positive control against elastase release induced by human neutrophils.
A 2025 study systematically explored the chemical composition of Semiaquilegiae Radix and its underlying anti-inflammatory mechanisms utilizing UHPLC-Q-TOF–MS/MS, network pharmacology, and molecular docking techniques. The chemical constituents were identified and characterized, relevant targets were predicted through databases such as PharmMapper and SwissTargetPrediction in conjunction with protein–protein interaction (PPI) network analysis, and Gene Ontology (GO) and KEGG enrichment analyses were performed.
The six core targets identified through PPI network and topological analysis in this study are IL6, ALB, AKT1, EGFR, SRC, and PPARG. These overlapping targets are involved in several critical signaling pathways, including the AGE-RAGE signaling pathway in diabetic complications and pathways related to lipid metabolism and atherosclerosis. Molecular docking showed that the primary seven active compounds can effectively bind to key targets.
4.2 Antioxidant Mechanisms in Lens Epithelial Cells
Semiaquilegia adoxoides root extract has been observed to provide a therapeutic effect on oxidative stress-related cataracts by decreasing the loss of mitochondrial membrane potential, decreasing the expression of apoptotic genes, promoting the expression of anti-apoptotic genes, and enhancing the cellular antioxidant capacity to decrease lens cell apoptosis and enhance cellular viability. Briefly, SA can treat oxidative stress-related cataracts via counteracting apoptosis.
4.3 Immunomodulatory Mechanisms
The polysaccharide SMP showed no direct antibacterial effects (both MIC values on E. coli and S. aureus were 250 ml/mL). However, mice experiments revealed that SMP had potential immunomodulatory effects by reducing WBC and the expression of serum IL-1, IL-6, and TNF-α and increasing IgM of E. coli or S. aureus–infected mice.
4.4 Antiproliferative (Anticancer) Mechanisms
The kauranoid semiaquilegin A has powerful cytotoxic activity. The corresponding triol, 16α,17,20-trihydroxy-ent-kaurane, has been synthesized from the more readily available oridonin. The exact mechanism of semiaquilegin A's antiproliferative action against cancer cell lines continues to be an active area of preclinical investigation.
5. Scientific Evidence by Area of Activity
5.1 Ocular Health: Cataract and Lens Epithelial Cell Protection
Traditional claim: The root of Semiaquilegia adoxoides is used in the TCM system to treat cataracts.
Scientific evidence (in vitro): One study aimed to investigate whether the n-butanol extract of S. adoxoides (nSA) is effective against H2O2-induced oxidative stress in human lens epithelial (HLE) cells. Human lens epithelial (SRA 01/04) cells were stimulated by H2O2 (250 μM) in the presence or absence of nSA. The antioxidant effects of nSA were determined in terms of cell viability (MTT assay), apoptosis (AnnexinV/PI staining), radical scavenging capability (various enzymatic assays), loss of mitochondrial membrane potential (Rhodamine 123 staining), and expression of apoptotic markers including caspase-3 and caspase-9, along with the change of Bcl-2/Bax ratio.
Evidence strength: This evidence is preclinical only (cell culture model). The study used a hydrogen peroxide–induced model, which is an accepted cellular model for oxidative stress but does not constitute clinical evidence in humans. No human clinical trials on S. adoxoides for cataract prevention or treatment have been identified in the peer-reviewed literature.
5.2 Anti-Inflammatory Activity
Scientific evidence (in vitro / computational): Semiaquilegiae Radix demonstrates significant anti-inflammatory potential. However, comprehensive investigations into its anti-inflammatory effects remain sparse.
The 2025 network pharmacology study by Shang et al. in the Saudi Pharmaceutical Journal used UHPLC-Q-TOF–MS/MS to identify constituents and employed in silico target prediction, molecular docking, and pathway enrichment analysis. The study did not include experimental animal or human data and is therefore classified as computational evidence only.
Earlier in vitro work using bioassay-guided fractionation demonstrated neutrophil-specific anti-inflammatory activity. 4-Hydroxybenzoic acid and 3,4-dihydroxybenzoic acid from S. adoxoides showed selective inhibition against elastase release and superoxide anion generation, with IC50 values of 3.20 and 6.21 μg/mL, respectively. This is in vitro evidence using isolated human neutrophils and cannot be directly extrapolated to clinical outcomes without further study.
Evidence strength: Preliminary; in vitro and computational only. No clinical trials have been identified.
5.3 Immunomodulatory and Antimicrobial-Related Activity
Scientific evidence (animal model): A 2020 study published in Evidence-Based Complementary and Alternative Medicine investigated the polysaccharide fraction (SMP) of S. adoxoides.
Mice were administered SMP for 7 days and then infected with E. coli or S. aureus, and the parameters were measured at the 9th day. Results showed that SMP was a furanose mainly composed of glucose (60.3%) and had certain antioxidant activities. Both MIC values of SMP on E. coli and S. aureus were 250 ml/mL, indicating that SMP has no direct antibacterial effects. The mice experiments revealed that SMP had potential immunomodulatory effects by reducing WBC and the expression of serum IL-1, IL-6, and TNF-α and increasing IgM of E. coli or S. aureus–infected mice.
According to ancient books, Semiaquilegia adoxoides can cure acute infectious diseases caused by S. aureus and E. coli in clinical infection, and the results of this experiment confirm this statement in some way. The study authors themselves noted that the trial is a preliminary study.
Evidence strength: Preclinical only (murine model). SMP did not directly kill bacteria at the tested concentrations; its beneficial effect appeared to be mediated by modulation of the host immune response rather than direct antimicrobial action. No human clinical trials have been identified.
5.4 Anticancer and Antiproliferative Activity
Scientific evidence (in vitro / cell line): Semiaquilegin A is a natural kaurane-type diterpenoid ester isolated from the roots of Semiaquilegia adoxoides (DC.) Makino, which exhibits antiproliferative activity against a broad spectrum of cancer cell lines with EC50 values ranging from 4.36 μM to 10.88 μM.
Research has also examined crude extracts of the root. One published study investigated the inhibitory effect of Radix Semiaquilegiae extract on human hepatoma HepG-2 and SMMC-7721 cells. This is a cell-line study, not a clinical trial. Pharmacological research indicated that the n-butanol extract of S. Makino protects human lens epithelial cells in oxidative stress induced by hydrogen peroxide, and the ethanol extraction of S. Makino has certain anticancer activity.
Evidence strength: Preclinical only (in vitro cell lines). The EC50 values reported for semiaquilegin A are within a range typically considered biologically meaningful in cancer cell-line screens, but these findings have not been validated in animal models or human clinical trials. Cell-line data cannot be used to predict clinical efficacy.
5.5 Use in Compound TCM Formulas: Gout Arthritis
Semiaquilegia adoxoides appears as a component in compound TCM formulas studied for gout-related inflammation. Semiaquilegia adoxoides (Tian Kui Zi, 10 g) is used as one ingredient in the classical decoction Wuwei Xiaodu Drink; the herbal materials are subjected to double decoction with eight times the volume of water for 1 hour, and the extracts combined, filtered, and concentrated. The study investigated whether the compound formula alleviates gout arthritis by suppressing NLRP3-mediated inflammation. Because S. adoxoides is one of multiple ingredients, specific effects attributable to S. adoxoides alone cannot be isolated from compound formula research of this type.
Evidence strength: The evidence from compound formula studies is indirect and cannot be used to attribute specific pharmacological effects to S. adoxoides alone.
6. Body Systems and Health Areas Associated with Semiaquilegia
- Ocular system: Traditional use for cataract; in vitro evidence for protection of human lens epithelial cells against oxidative stress.
- Immune system / Inflammatory response: Reduction of pro-inflammatory cytokines (IL-1, IL-6, TNF-α) in murine infection models; network pharmacology identification of inflammatory signaling targets (IL6, AKT1, EGFR, SRC, PPARG).
- Skin and lymphatic system: Traditional TCM use for carbuncles, furuncles, breast abscesses, and lymph node tuberculosis (scrofula).
- Oncology (preclinical): Antiproliferative activity of semiaquilegin A and ethanolic extracts against cancer cell lines in vitro.
- Urinary system: Traditional TCM use as a diuretic for difficulty in urination.
- Toxicology / Snakebite: Folk use for snakebite treatment, cited in multiple ethnobotanical and phytochemical sources.
7. Dosage Forms and Dosages Reported in the Scientific Literature
No standardized human dosages are established in any regulatory pharmacopoeia reviewed. The following dosages and preparation methods appear in the peer-reviewed and pharmacopoeial literature:
- Compound decoction (TCM clinical formula): Semiaquilegia adoxoides (Tian Kui Zi) is used at 10 g as a component of Wuwei Xiaodu Drink. The materials are subjected to double decoction with eight times the volume of water for 1 hour, the extracts combined, filtered, and concentrated to a final volume of 50 mL corresponding to a concentration of 1 g/mL.
- n-Butanol extract (in vitro study): Human lens epithelial (SRA 01/04) cells were stimulated by H2O2 (250 μM) in the presence or absence of nSA — the extract concentration used was defined by the experimental protocol; this does not represent a human dose.
- Polysaccharide fraction (SMP) — animal study: Mice were administered SMP for 7 days and then infected with E. coli or S. aureus, and the parameters were measured at the 9th day. Specific doses administered in mg/kg to mice are not reported in the available portions of the full text.
No human clinical trial dosing data for Semiaquilegia adoxoides administered as a single agent have been identified in the peer-reviewed literature.
8. Safety Considerations
8.1 Noted Toxicity in Traditional Sources
In traditional source descriptions, Semiaquilegia adoxoides is characterized as slightly toxic. The whole plant is also described as usable as a botanical pesticide, which is consistent with the presence of biologically active compounds capable of affecting biological systems.
8.2 Cyano-Containing Compounds
Some cyano-containing compounds, which are very rare in plants, have been reported from the traditional anticancer herb Tiankuizi. The isolation of the chemical constituents was investigated for advancing research in these compounds. Cyano-containing (nitrile-bearing) secondary metabolites warrant attention from a toxicological standpoint, though specific toxicity data for these compounds isolated from S. adoxoides are not detailed in the peer-reviewed literature identified.
8.3 Magnoflorine: Safety Profile Observations
Magnoflorine, an alkaloid present in S. adoxoides, has been studied separately. Toxicity studies have suggested that magnoflorine is non-toxic to most cells. However, long-term and high-dose toxicity testing in animals is still lacking. Pharmacokinetic studies have shown that magnoflorine has low bioavailability and high absorption and elimination rates.
8.4 Absence of Clinical Safety Data
No human clinical trials assessing the safety of Semiaquilegia adoxoides as a single-agent supplement have been identified in the peer-reviewed literature. Safety conclusions cannot be drawn from the available preclinical data alone. The traditional characterization of the plant as "slightly toxic" is consistent with the biological activity of several identified constituents, but quantitative safety thresholds for human exposure have not been established in published research.
8.5 Pesticide Activity
The tuberous root can be used as a botanical pesticide, suggesting the presence of compounds with bioactivity sufficient to affect living organisms beyond microbes. This characteristic is noted in risk assessments of plants with pesticidal properties.
9. Current State of Evidence: Overall Summary
The scientific evidence base for Semiaquilegia adoxoides as a dietary supplement or medicinal plant is preliminary and preclinical. The bulk of published research consists of:
- Phytochemical isolation and characterization studies (identifying and structurally characterizing compounds).
- In vitro cell-line studies (anticancer, ocular cell protection).
- In vitro and computational anti-inflammatory studies.
- One murine immunomodulatory study.
- Network pharmacology and molecular docking analyses (computational, no experimental confirmation in animals or humans).
There are no published randomized controlled trials, cohort studies, case-control studies, or clinical case series examining the efficacy or safety of Semiaquilegia adoxoides as a standalone intervention in humans. Its inclusion in the Chinese Pharmacopoeia reflects its recognized status in TCM practice, but this does not constitute evidence of clinical efficacy by contemporary evidence-based medicine standards. All efficacy and safety conclusions from existing research must be considered provisional and subject to revision pending further investigation.
References
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