Corydalis ambigua
StarCorydalis ambigua
Synonyms: Capnoides ambigua, Pistolochia ambigua, Corydalis jezoensis, Corydalis ambigua var. papillosa, Capnoides jezoensis
Safety at a glance
No rule in our tables for this herb: pregnancy, breastfeeding, incompatible pairs (十八反 / 十九畏), herb–drug, dose ceiling. This is not a safety clearance.
Not graded — No toxicity grade is recorded. Most herbs in the catalogue carry none.
Traditionally used for
- Digestion
- Menstrual & women's health
- Pain & joints
Cautions & contraindications
- Young children
- Liver conditions
Western Herbalism Properties
Traditional Uses
In Japanese kanpō medicine the dried tuber of Corydalis ambigua is one of the accepted source species for the crude drug 延胡索 engosaku (Chinese yán hú suǒ), traditionally indicated for the relief of internal pain — gastric pain, dysmenorrhoea, abdominal cramping and traumatic pain — in formulae such as An-chū-san. Tsumura kanpō pharmacopoeial monographs list C. ambigua tuber among the permitted botanical origins of the drug alongside C. yanhusuo and C. turtschaninovii, with activity attributed principally to isoquinoline alkaloids of the protoberberine and aporphine classes (notably tetrahydropalmatine and corydaline), which underlie the analgesic and antispasmodic actions catalogued in modern East Asian pharmacology (Tsumura kanpō literature; cf. Bensky, 2004, Chinese Herbal Medicine: Materia Medica, 3rd ed.).
Botanical Description
Corydalis ambigua Cham. & Schltdl. is a small spring-ephemeral perennial herb of the Papaveraceae (subfamily Fumarioideae) native to north-eastern Asia, ranging from the Russian Far East (Kamchatka, Sakhalin, Primorye) through north-eastern China (Heilongjiang, Jilin), Korea and Japan (Hokkaido, northern Honshu). It grows from a small, globose underground tuber (a corm-like swollen rhizome) 1–2 cm across, sending up a single slender, glabrous stem 10–25 cm tall in early spring before the deciduous forest canopy closes. The basal and stem leaves are biternately compound, with delicate, glaucous-green, deeply divided segments. The inflorescence is a short terminal raceme of 5–15 flowers; each flower is zygomorphic, about 1.5–2.5 cm long, sky-blue to pale blue-violet (rarely whitish or pink), with a long basal spur typical of the genus. The slender capsular fruit dehisces to release small black seeds bearing a fleshy elaiosome dispersed by ants. The plant dies back to the tuber in early summer.
Active Constituents
dl-Tetrahydropalmatine
Tetrahydroprotoberberine alkaloidConcentration: Isolated from the tuber and rhizome as the racemate in the classical Japanese work on this species
The alkaloid that carries the analgesic and sedative reputation of the whole Corydalis group. The levorotatory enantiomer is a mixed dopamine receptor antagonist, binding D1 and D2 with low D3 affinity, and it is the compound behind the analgesic, sedative and hypnotic use of these tubers. It is also the compound responsible for the human toxicity seen when concentrated tetrahydropalmatine products are taken in overdose.
Dehydrocorydaline
Quaternary protoberberine alkaloidConcentration: One of four quaternary protoberberine bases isolated from the rhizome of this species
A quaternary protoberberine typical of the Yan Hu Suo alkaloid pattern. Quaternary alkaloids are permanently charged and absorbed far less well than the tetrahydro bases, so their contribution to an oral decoction is different from what cell-culture potency would suggest.
Corybulbine and dehydrocorybulbine
Protoberberine alkaloidsConcentration: Isolated from the rhizome of this species; corybulbine identified as the d-enantiomer
Corybulbine is a tertiary tetrahydroprotoberberine and dehydrocorybulbine its quaternary counterpart. Both belong to the alkaloid set that defines the Corydalis tubers used for pain, and their presence is one of the reasons the chemistry of this species is indistinguishable in kind from that of the pharmacopoeial Yan Hu Suo.
Canadine (tetrahydroberberine)
Tetrahydroprotoberberine alkaloidConcentration: Isolated among the tertiary bases of the rhizome of this species
The tetrahydro form of berberine. Like tetrahydropalmatine it is a neutral tertiary base that crosses the blood-brain barrier, which is why the tetrahydroprotoberberines rather than the quaternary alkaloids account for the central effects of these tubers.
Palmatine
Quaternary protoberberine alkaloidConcentration: One of the quaternary protoberberines isolated from the rhizome of this species
A quaternary protoberberine shared with Coptis and Phellodendron. In this drug it is a minor constituent rather than a principal active, and its presence complicates chemical fingerprinting because it is not specific to the genus.
Acetylcorynoline
Benzophenanthridine alkaloidConcentration: Isolated from the tubers of this species; oral bioavailability in mice 58.9 percent with a half-life of about 2.6 hours
A benzophenanthridine, structurally unrelated to the protoberberines and reported specifically from the tubers of this species. It has anti-inflammatory activity with proposed relevance to Parkinson's disease, and in colon cancer cells it induced apoptosis and G2/M arrest by suppressing c-Myc through CNOT2 and MID1IP1, acting synergistically with low-dose 5-fluorouracil and doxorubicin. It is the one alkaloid whose literature is genuinely attached to this species rather than to the drug Yan Hu Suo.
⚠ Drug Interactions
Yan Hu Suo (Corydalis yanhusuo tuber)
This is the single most important thing to know about this record. A large part of the twentieth-century pharmacology published under the name Corydalis ambigua is in fact about the drug Yan Hu Suo: T.Q. Chou's 1928 alkaloid paper is titled for Chinese Corydalis ambigua and glosses it as Yen-Hu-So, and the Japanese alkaloid series on Corydalis ambigua var. amurensis, ezo-engosaku, recovered exactly the Yan Hu Suo alkaloid set of tetrahydropalmatine, canadine, corybulbine, dehydrocorybulbine, dehydrocorydaline and palmatine. Current nomenclature separates Corydalis yanhusuo, the Chinese Pharmacopoeia source of Yan Hu Suo, from Corydalis ambigua, an accepted species of Japan, Korea and the Russian Far East, but DNA barcoding shows Corydalis species limits are genuinely unstable, with several traditionally recognised species collapsing into one genetic species. Commercial confusion is documented too: a survey of fourteen Corydalis yanhusuo supplements found total alkaloid content ranging from unquantifiable to about 11 mg per gram, and one product so enriched in tetrahydropalmatine as to suggest deliberate adulteration.
Clinical note: Do not treat a study or a dose that names Corydalis ambigua as evidence about this species without checking what plant was actually used; before about 1980 it usually means Yan Hu Suo. If a practitioner wants Yan Hu Suo, dispense pharmacopoeial Corydalis yanhusuo, and record which was supplied.
Benzodiazepines, opioids, alcohol and other CNS depressants
Levo-tetrahydropalmatine, the principal alkaloid of these tubers, is a sedative and hypnotic and a mixed dopamine receptor antagonist. Its capacity for serious human harm is documented through Jin Bu Huan Anodyne Tablets, a concentrated tetrahydropalmatine product: a single acute ingestion in each of three children rapidly produced life-threatening neurological and cardiovascular effects. That product was mislabelled and was not Corydalis, so the evidence bears on the alkaloid rather than on this herb, but the alkaloid is the same one and a crude tuber decoction simply delivers less of it.
Clinical note: Warn patients about additive sedation and impaired driving when this herb is combined with benzodiazepines, opioids, sedating antihistamines, alcohol or sleep medication. Do not use concentrated tetrahydropalmatine extracts alongside CNS depressants, and keep any Corydalis product away from children.
Antipsychotics, levodopa and dopamine agonists
Levo-tetrahydropalmatine binds dopamine D1 and D2 receptors, with low affinity for D3, and behaves as an antagonist; in rodents it reduced methamphetamine self-administration and drug-seeking reinstatement at doses that did not impair locomotion. Adding a dopamine antagonist to an antipsychotic is expected to be additive for extrapyramidal effects, and adding it to levodopa or a dopamine agonist is expected to oppose the intended effect. No human interaction study has been done.
Clinical note: Avoid in Parkinson's disease and in patients on dopamine agonists. In patients on antipsychotics, watch for new stiffness, tremor or restlessness after starting the herb. The mechanism is well characterised but the clinical interaction has not been measured in people.
Paracetamol, methotrexate, isoniazid and other hepatotoxic drugs
Prolonged use of the concentrated tetrahydropalmatine product Jin Bu Huan produced acute hepatitis in seven previously healthy adults after a mean of 20 weeks, resolving over a mean of 8 weeks; reducing the dose improved liver tests in one patient and rechallenge caused abrupt recurrence in two, which is about as strong as causality gets outside a trial. Biopsies showed hepatitis with eosinophils in one case and fibrosis with microvesicular steatosis in another, consistent with either hypersensitivity or a reactive metabolite. The implicated product was mislabelled and was not Corydalis, but the alkaloid is shared, and a herb with a hepatitis signal should not be stacked with drugs that carry one.
Clinical note: Do not use long-term without liver function monitoring, and be cautious about combining with hepatotoxic drugs or in existing liver disease. Stop the herb and check liver enzymes if fatigue, nausea, jaundice or right upper quadrant pain appear.
QT-prolonging drugs
Benzyltetrahydropalmatine, a derivative of the tetrahydropalmatine extracted from this species, reversibly blocked the hERG potassium current in HEK293 cells with an IC50 of 22.38 micromolar, shifted steady-state inactivation negatively and prolonged recovery from inactivation. This is a synthetic derivative rather than a constituent of the tuber, and the parent alkaloid was not tested, so this is a flag for further work rather than a demonstrated risk of the herb.
Clinical note: No action is required on this evidence alone. Mentioned so that a practitioner encountering the hERG literature on Corydalis derivatives knows it concerns a semisynthetic compound and not the crude drug.
Dosage Calculator
⚖ Dosage Calculator
A weight-based mathematical estimate for Corydalis ambigua. Not a prescription.
Evidence Tier
6 studies on recordRecorded studies by study design, strongest design at the top. This is a study-design tier only, not a GRADE rating: it does not weigh risk of bias, consistency or precision.
Systematic review / meta-analysis
0
Randomized controlled trial
0
Other clinical trial
0
Observational / case report
2
1 verified · 1 unverified
In vitro / animal
4
1 verified · 3 unverified
Show 4 studies
- Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells
- Determination and Pharmacokinetics of Acetylcorynoline in Mouse Plasma by UPLC-MS/MS
- Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement
- Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells
Other / unclassified
0
Verified: design read from PubMed for a DOI that resolves to the cited paper Unverified: taken from the study's recorded description
Clinical Studies
Acute Hepatitis Associated with the Chinese Herbal Product Jin Bu Huan
Retrospective case series of seven previously healthy adults who developed acute hepatitis after a mean of 20 weeks of Jin Bu Huan Anodyne Tablets, resolving over a mean of 8 weeks. Dose reduction improved liver tests in one patient and rechallenge caused abrupt recurrence in two. Biopsy showed hepatitis with eosinophils in one case and mild hepatitis with moderate fibrosis and microvesicular steatosis in another. The product was labelled as Lycopodium serratum and was not Corydalis; the toxin was subsequently identified as levo-tetrahydropalmatine, the principal alkaloid of Corydalis tubers, which is why this series bears on this herb at all.
The Clinical Spectrum of Jin Bu Huan Toxicity
Case series of three children and three adults poisoned by Jin Bu Huan Anodyne Tablets. Acute ingestion in children caused rapid life-threatening neurological and cardiovascular effects; prolonged use in adults caused hepatitis. The paper identifies levo-tetrahydropalmatine as the responsible neuroactive alkaloid and records that the package misidentified the plant, delaying diagnosis. Again the product was not Corydalis, but it defines the human toxicity profile of the alkaloid this herb contains.
Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells
Acetylcorynoline, stated to be derived from the tubers of Corydalis ambigua, reduced colon cancer cell viability and proliferation, induced apoptosis and G2/M arrest, shortened the half-life of the c-Myc protein and lowered oncogene expression through CNOT2 and MID1IP1, and acted synergistically with low-dose 5-fluorouracil and doxorubicin. Cell-culture work only; no animal or human oncology data.
Determination and Pharmacokinetics of Acetylcorynoline in Mouse Plasma by UPLC-MS/MS
A UPLC-MS/MS assay for acetylcorynoline, described as an alkaloid isolated from the tubers of Corydalis ambigua, was validated in mouse plasma and applied after 5 mg per kg intravenous and 20 mg per kg oral dosing. Half-life was about 2.6 to 2.7 hours by either route and absolute oral bioavailability was 58.9 percent. Mouse pharmacokinetics; useful because it is one of the few quantitative datasets attached to a compound specifically from this species.
Levo-tetrahydropalmatine, a natural, mixed dopamine receptor antagonist, inhibits methamphetamine self-administration and methamphetamine-induced reinstatement
Levo-tetrahydropalmatine, described as derived from Corydalis and Stephania and as binding D1 and D2 receptors with low D3 affinity, reduced methamphetamine self-administration at 1.25 to 5.00 mg per kg intraperitoneally in rats and blocked methamphetamine-induced reinstatement at 2.50 and 5.00 mg per kg, without impairing locomotion at the lower doses. Rodent addiction model; its relevance here is that it characterises the dopamine antagonism that underlies the herb's interaction with antipsychotics and antiparkinsonian drugs.
Allocryptopine and benzyltetrahydropalmatine block hERG potassium channels expressed in HEK293 cells
Benzyltetrahydropalmatine, a derivative of the tetrahydropalmatine extracted from Corydalis ambigua, blocked hERG current in transfected HEK293 cells with an IC50 of 22.38 micromolar, negatively shifted steady-state inactivation and lengthened recovery from inactivation; allocryptopine, from Corydalis decumbens, blocked with an IC50 of 49.65 micromolar. Patch-clamp study of a semisynthetic derivative, not of the crude herb or of the parent alkaloid.
Historical Texts
Ben Cao Gang Mu (Compendium of Materia Medica)
Ming dynasty, 1596Early twentieth-century pharmacognostic literature published under the name Corydalis ambigua
1920s to 1970sReferences
- T.-Q. Chou. Some New Alkaloids from Chinese Corydalis Ambigua, Cham. et. Sch. (Yen-Hu-So). . Experimental Biology and Medicine (1928) [DOI]
- Izumi Imaseki, Heihachiro Taguchi. Studies on the Components of Corydalis spp. I . YAKUGAKU ZASSHI (1962) [DOI]
- Heihachiro Taguchi, Izumi Imaseki. Studies on the Components of Corydalis spp. III . YAKUGAKU ZASSHI (1964) [DOI]
- Shunsuke Naruto, Hidehiko Kaneko. Alkaloids from Corydalis ambigua . Phytochemistry (1973) [DOI]
- Lu Jiang, Meihui Li, Fengxi Zhao, Shanshan Chu, Liangping Zha, Tao Xu, Huasheng Peng, Wei Zhang. Molecular Identification and Taxonomic Implication of Herbal Species in Genus Corydalis (Papaveraceae) . Molecules (2018) [DOI]
- Paula B. Luis, Claus Schneider. Large variability in the alkaloid content of Corydalis yanhusuo dietary supplements . Frontiers in Pharmacology (2025) [DOI]
- Lamees Alhassen, Travis Dabbous, Allyssa Ha, Leon Hoang Lam Dang, Olivier Civelli. The Analgesic Properties of Corydalis yanhusuo . Molecules (2021) [DOI]
This information is for educational purposes only and is not intended to replace professional medical advice. Always consult a qualified healthcare provider before using any herbal remedy, especially if you are pregnant, nursing, or taking medications.
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