Asparagamine A

Asparagamine A at a Glance

Asparagamine A is a caged pentacyclic alkaloid — C₂₂H₂₇NO₅, molecular weight 385.5 — built on the pyrrolo[1,2-a]azepine nucleus that defines the Stemona alkaloids, bridged into a rigid polycyclic cage and capped with a methoxy-methyl butenolide and a but-1-enyl side chain ^{1,4,8Reference 1Sekine T et al. · 1994Structure of asparagamine A, a novel polycyclic alkaloid from Asparagus racemosusView study →Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →Reference 8Greger H · 2006Structural relationships, distribution and biological activities of Stemona alkaloidsView study →}. Sekine and colleagues described it in 1994 as a “new cage-type alkaloid.. novel polycyclic pyrrolizidine derivative”, solved by single-crystal X-ray ^{1Reference 1Sekine T et al. · 1994Structure of asparagamine A, a novel polycyclic alkaloid from Asparagus racemosusView study →}.

Two things make it worth a page, and neither is a health benefit.

First, the name is wrong. It was named for Asparagus racemosus — shatavari — because that is what the roots it came from were sold as. In 2004 Austrian workers showed the molecule is identical to 1’,2’-didehydrostemofoline from Stemona collinsiae ^{4Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →}, and in 2013 Japanese regulators at the National Institute of Health Sciences analysed authenticated A. racemosus plants and commercial shatavari products and found no asparagamine A in any of them ^{3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →}. Shatavari does not make this molecule. Stemona does, and Stemona tubers look enough like shatavari root to be substituted for them.

Second, the structure was hard enough to be worth building. The cage attracted a decade of synthetic effort culminating in Overman’s 2003 total synthesis ^{15Reference 15Brüggemann M et al. · 2003Total synthesis of (±)-didehydrostemofoline (asparagamine A) and (±)-isodidehydrostemofolineView study →}, with formal and core syntheses from Gin, Martin and Livinghouse either side of it ^{16,17,18,19Reference 16Epperson MT · 2002Enantiospecific synthesis of the bridged pyrrolizidine core of asparagamine A: dipolar cycloadditions of azomethine ylides derived from the sulfonylation of vinylogous amidesView study →Reference 17Fang C et al. · 2012Enantioselective formal total syntheses of didehydrostemofoline and isodidehydrostemofoline through a catalytic dipolar cycloaddition cascadeView study →Reference 18Shanahan CS et al. · 2013Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution, development and application of a catalytic dipolar cycloaddition cascadeView study →Reference 19Anderson BK · 2015Divergent stereocontrolled synthesis of the enantiopure tetracyclic cores of asparagamine A and stemofoline via an intramolecular 2-propylidine-1,3-(bis)silane bicyclizationView study →}. On any honest count the synthetic-chemistry literature on this molecule is larger and better than its pharmacology, which amounts to a potent insecticide, an unread 1995 anti-oxytocin claim, and a P-glycoprotein result.

The Shatavari Attribution Error

This is the single most important thing on the page, so it goes first.

1994 — the isolation. Sekine’s group at Chiba University, working with Nijsiri Ruangrungsi in Bangkok, isolated a new cage alkaloid from roots identified as Asparagus racemosus Willd. and named it asparagamine A ^{1Reference 1Sekine T et al. · 1994Structure of asparagamine A, a novel polycyclic alkaloid from Asparagus racemosusView study →}. A companion 1995 paper in J. Chem. Soc. Perkin Trans. 1 reported its relative stereochemistry and, in its title, anti-oxytocin activity ^{2Reference 2Sekine T et al. · 1995Structure and relative stereochemistry of a new polycyclic alkaloid, asparagamine A, showing anti-oxytocin activity, isolated from Asparagus racemosusView study →}. Because shatavari’s headline traditional use is as a female reproductive tonic, an anti-oxytocic constituent was a satisfying result, and it entered the review literature immediately.

2004 — the structural identity. Seger, Greger and colleagues in Vienna solved X-ray structures for 2’-hydroxystemofoline and inferred the configuration of 1’,2’-didehydrostemofoline from Stemona collinsiae, and concluded that asparagamine A is the same compound. Their stated inference: the reported plant source of asparagamine A was most likely a Stemona species ^{4Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →}.

2013 — the confirmation. Kumeta and colleagues at Japan’s National Institute of Health Sciences DNA-typed shatavari products on the Japanese market, confirmed by steroidal-saponin profiling that they really were Asparagus racemosus, then ran alkaloid analysis on both the products and an authentic A. racemosus plant. Neither contained asparagamine A. Their conclusion is unambiguous: A. racemosus does not contain it, and earlier isolations from material said to originate from A. racemosus were most likely misidentified Stemona ^{3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →}.

Why the mix-up is easy. Stemona species have clustered tuberous roots of very similar shape and colour to shatavari root, and they are traded in the same Southeast Asian markets. Pyrrolo[1,2-a]azepine alkaloids are, so far as anyone knows, exclusive to the Stemonaceae ^{8Reference 8Greger H · 2006Structural relationships, distribution and biological activities of Stemona alkaloidsView study →} — so finding one in a lily-family root was always the anomaly, not the discovery.

The error is still propagating. A DPPH-guided antioxidant study from Chulalongkorn University in 2004 reports asparagamine A among the compounds isolated from A. racemosus roots ^{20Reference 20Wiboonpun N et al. · 2004Identification of antioxidant compound from Asparagus racemosusView study →} — the paper the original entry rested on. The NIH LactMed monograph for wild asparagus still lists “asparagamine” among shatavari’s constituents ^{21Reference 21Wild Asparagus · 2006In: Drugs and Lactation Database (LactMed) [Internet]View study →}. A 2025 molecular-docking screen nominates asparagamine A as a lead antileishmanial from a library of Indian medicinal plant phytochemicals ^{22Reference 22Arya PK et al. · 2026Targeting spermidine synthase in Leishmania donovani: molecular docking and molecular dynamics simulation-based evaluation of Indian medicinal plant phytochemicalsView study →}. None of these is dishonest; they are all downstream of a 1994 name that nobody re-checked.

What therefore cannot be said. It does not treat asparagamine A as a shatavari constituent, does not carry its “antioxidant” reputation forward, and does not use it to explain anything about how shatavari works. Shatavari’s pharmacology rests on its steroidal saponins — the shatavarins, built on the sarsasapogenin aglycone — plus its fructo-oligosaccharides and phenolics, none of which are affected by this correction.

What It's Used For

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every score here is capped low: there are no human data of any kind, and the total PubMed literature under the name asparagamine is ten records. Each application links to its write-up.

01Insecticidal & AntifeedantShaky42%Multiple independent groups, quantitative, isolate-level ^{5,6,8,11Reference 5Jiwajinda S et al. · 2001Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsaeView study →Reference 6Brem B et al. · 2002Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticidesView study →Reference 8Greger H · 2006Structural relationships, distribution and biological activities of Stemona alkaloidsView study →Reference 11Chalom S et al. · 2021Cytotoxic and larvicidal activities of Stemona alkaloids from the aerial parts and roots of Stemona curtisii Hook.fView study →}

02AnthelminticShaky22%Rat in-vivo work on a standardised extract, not the isolate ^{13,14Reference 13Arlee N et al. · 2024Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profilesView study →Reference 14Arlee N et al. · 2024AnimalLC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administrationView study →}

03P-Glycoprotein & MDR ReversalShaky20%One cell-line study, both isomers, with a normal-cell control ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}

04Anti-Oxytocin ActivityShaky8%A single 1995 paper, unreplicated, wrong source plant ^{2Reference 2Sekine T et al. · 1995Structure and relative stereochemistry of a new polycyclic alkaloid, asparagamine A, showing anti-oxytocin activity, isolated from Asparagus racemosusView study →}

05AntioxidantShaky4%Co-isolation in a DPPH-guided fractionation; no IC₅₀ published ^{20Reference 20Wiboonpun N et al. · 2004Identification of antioxidant compound from Asparagus racemosusView study →}

Mechanisms

Pharmacokinetics

Unusually for a molecule this obscure, real pharmacokinetics exist. A 2024 Mahidol study developed and validated an LC-MS/MS assay for didehydrostemofoline in rat plasma and applied it after oral administration of standardised S. collinsiae root extract ^{14Reference 14Arlee N et al. · 2024AnimalLC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administrationView study →}:

Parameter	Value (rat, oral extract)
Tmax	1.75 ± 0.62 h
Cmax	1,152.58 ± 271.18 ng/mL
Terminal half-life	1.86 ± 0.50 h
Apparent clearance	96.82 ± 23.51 L/h
Apparent volume of distribution	260.40 ± 96.81 L

The interpretable findings are the first three: it is rapidly absorbed from the gastrointestinal tract and rapidly eliminated, with a sub-two-hour half-life. The clearance and volume figures are reported without body-weight normalisation and without the administered dose in the abstract, so they should not be read as rat-specific constants.

This is a real contrast with the large glycosides and tannins that dominate the herbal literature: at 385 Da, lipophilic and un-glycosylated, asparagamine A does reach plasma. Whether it reaches any target of human relevance once there is entirely unstudied.

Clinical Trials

None. There is no clinical trial of asparagamine A under any of its names, and no registered study. Human exposure is limited to whatever occurs when Stemona root is used traditionally, or when Stemona material is substituted for shatavari in commerce — which is exactly the substitution the 2013 analysis was designed to detect ^{3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →}.

Last checked: August 2026.

Isolate vs. Plant

The isolate/plant line is drawn in an unusual place here, because the plant most people associate with the molecule is the wrong plant.

Where the isolate did the work: the insecticidal structure–activity comparisons ^{5,6Reference 5Jiwajinda S et al. · 2001Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsaeView study →Reference 6Brem B et al. · 2002Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticidesView study →}, the mosquito larvicidal LC₅₀ ^{11Reference 11Chalom S et al. · 2021Cytotoxic and larvicidal activities of Stemona alkaloids from the aerial parts and roots of Stemona curtisii Hook.fView study →}, the P-glycoprotein assays ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}, and its use as the semisynthetic starting material for oxystemofoline and methoxystemofoline in acetylcholinesterase work — where, note, the most active AChE inhibitor was an analogue, and it was still weaker than galantamine ^{25Reference 25Sastraruji K et al. · 2010Semisynthesis and acetylcholinesterase inhibitory activity of stemofoline alkaloids and analoguesView study →}.

Where the extract did the work: the anthelmintic and toxicity results, in which asparagamine A serves only as the HPLC marker used to standardise the preparation ^{13,14Reference 13Arlee N et al. · 2024Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profilesView study →Reference 14Arlee N et al. · 2024AnimalLC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administrationView study →}. A standardisation marker is not an active ingredient, and the two are constantly conflated in Stemona product literature.

Where neither did the work: every claim that runs from this molecule to shatavari. There is no transfer to make, because there is no molecule in the plant ^{3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →}.

Prevalence in Nature

Pyrrolo[1,2-a]azepine alkaloids of this type are, on current evidence, restricted to the family Stemonaceae — three genera, mostly Southeast Asian ^{8Reference 8Greger H · 2006Structural relationships, distribution and biological activities of Stemona alkaloidsView study →}. Within that family, accumulation is strikingly species-specific, which is why these alkaloids work as chemotaxonomic markers.

Source	Part	Basis
Stemona collinsiae (syn. S. collinsae)	Roots	The true source and the richest — didehydrostemofoline is its species-specific chemical marker 7,10Reference 7Schinnerl J et al. · 2007Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona speciesView study →Reference 10Kongkiatpaiboon S et al. · 2011Structural relationships of Stemona alkaloids: assessment of species-specific accumulation trends for exploiting their biological activitiesView study →; averaged 0.78% w/w of the root extract across eight samples, against 0.048% for stemofoline 9Reference 9Kongkiatpaiboon S · 2012HPLC quantitative analysis of insecticidal didehydrostemofoline and stemofoline in Stemona collinsiae root extractsView study →
Stemona curtisii	Aerial parts	(11Z)-1’,2’-Didehydrostemofoline isolated alongside stemocurtisine and related alkaloids 11Reference 11Chalom S et al. · 2021Cytotoxic and larvicidal activities of Stemona alkaloids from the aerial parts and roots of Stemona curtisii Hook.fView study →
Stemona aphylla	Roots	Stemofoline-type alkaloids including didehydrostemofoline in the accumulation profile 10Reference 10Kongkiatpaiboon S et al. · 2011Structural relationships of Stemona alkaloids: assessment of species-specific accumulation trends for exploiting their biological activitiesView study →
Asparagus racemosus (shatavari)	Root	Not present. Authenticated plant material and market products both tested negative 3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →

A 2007 survey of 31 Stemona species and provenances found the unique accumulation of didehydrostemofoline to be the chemical signature of S. collinsae specifically ^{7Reference 7Schinnerl J et al. · 2007Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona speciesView study →}, and a 2011 comparison across 42 samples of eight species confirmed that S. curtisii and S. collinsiae are the stemofoline/didehydrostemofoline accumulators while S. tuberosa and S. phyllantha run to tuberostemonine instead ^{10Reference 10Kongkiatpaiboon S et al. · 2011Structural relationships of Stemona alkaloids: assessment of species-specific accumulation trends for exploiting their biological activitiesView study →}. The practical consequence is that “Stemona extract” is not one thing — the alkaloid profile, and therefore the insecticidal potency, depends entirely on which species was collected.

Discovery & Synthesis

This is the section with the most in it, because the synthetic-chemistry story is genuinely larger than the pharmacology.

Isolation & Structure

1994. Toshikazu Sekine, Nobuaki Fukasawa, Yumi Kashiwagi, Nijsiri Ruangrungsi and Isamu Murakoshi reported a new cage-type alkaloid from roots identified as Asparagus racemosus Willd., naming it asparagamine A. The relative stereostructure was settled by spectroscopic, chemical and single-crystal X-ray analysis, and described as a novel polycyclic pyrrolizidine derivative ^{1Reference 1Sekine T et al. · 1994Structure of asparagamine A, a novel polycyclic alkaloid from Asparagus racemosusView study →}. 1995. A fuller account in J. Chem. Soc. Perkin Trans. 1 gave the relative stereochemistry and reported anti-oxytocin activity ^{2Reference 2Sekine T et al. · 1995Structure and relative stereochemistry of a new polycyclic alkaloid, asparagamine A, showing anti-oxytocin activity, isolated from Asparagus racemosusView study →}. 2001. Independently, a Thai–Japanese group reported the same skeleton as 16,17-didehydro-16(E)-stemofoline from Stemona collinsae, together with its C-4 isomer and stemofoline, and noted it was the more insecticidal of the pair ^{5Reference 5Jiwajinda S et al. · 2001Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsaeView study →}. 2004. Seger, Mereiter, Kaltenegger, Pacher, Greger and Hofer closed the loop: X-ray and NMR comparison established that asparagamine A is 1’,2’-didehydrostemofoline, and that the reported source was most likely a Stemona ^{4Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →}. 2013. Kumeta and colleagues confirmed the absence from authentic A. racemosus ^{3Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →}.

The molecule is registered as PubChem CID 56666692, ChEBI:70413, C₂₂H₂₇NO₅, MW 385.5 — under the name didehydrostemofoline, with asparagamine A surviving only as a synonym.

Why It Became a Synthesis Target

The appeal is structural, not medicinal. The core is a pentacyclic cage containing a bridged azabicyclic system, two oxygen-containing rings, seven contiguous stereocentres, an anhydride-free but highly oxygenated architecture, and a stereodefined exocyclic butenolide with a pendant but-1-enyl chain whose geometry distinguishes the natural product from its “iso” congener. Building a strained bridged cage while controlling that many centres — and then installing the alkene geometry last — is a genuinely hard problem, which is why it drew four separate research programmes.

Year	Group	Achievement	Ref
2002	Epperson & Gin (Illinois)	Enantiospecific synthesis of the bridged pyrrolizidine core, via dipolar cycloaddition of azomethine ylides from sulfonylation of vinylogous amides	16Reference 16Epperson MT · 2002Enantiospecific synthesis of the bridged pyrrolizidine core of asparagamine A: dipolar cycloadditions of azomethine ylides derived from the sulfonylation of vinylogous amidesView study →
2003	Brüggemann, McDonald, Overman, Rosen, Schwink & Scott (UC Irvine)	First total synthesis of (±)-didehydrostemofoline (asparagamine A) and (±)-isodidehydrostemofoline	15Reference 15Brüggemann M et al. · 2003Total synthesis of (±)-didehydrostemofoline (asparagamine A) and (±)-isodidehydrostemofolineView study →
2012	Fang, Shanahan, Paull & Martin (UT Austin)	Enantioselective formal total syntheses of both isomers, 24 steps from 2-deoxy-D-ribose	17Reference 17Fang C et al. · 2012Enantioselective formal total syntheses of didehydrostemofoline and isodidehydrostemofoline through a catalytic dipolar cycloaddition cascadeView study →
2013	Shanahan, Fang, Paull & Martin (UT Austin)	Full account of the catalytic dipolar-cycloaddition cascade, intercepting an Overman intermediate	18Reference 18Shanahan CS et al. · 2013Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution, development and application of a catalytic dipolar cycloaddition cascadeView study →
2015	Anderson & Livinghouse (Montana State)	Divergent stereocontrolled synthesis of the enantiopure tetracyclic cores of asparagamine A and stemofoline	19Reference 19Anderson BK · 2015Divergent stereocontrolled synthesis of the enantiopure tetracyclic cores of asparagamine A and stemofoline via an intramolecular 2-propylidine-1,3-(bis)silane bicyclizationView study →

Overman’s route (2003) opens with a Diels–Alder reaction between a pyrrole and ethyl (E)-3-nitroacrylate — the nitroacrylate acting as a regio-inverted ketene equivalent — then hydrogenates the adduct to block retro-Diels–Alder, converts it to a 7-azabicyclo[2.2.1]heptanol, and uses an aza-Cope–Mannich reaction on the formaldiminium derivative to deliver the 1-azatricyclo[5.3.0.0⁴,¹⁰]decane. Fifteen further steps give both natural products ^{15Reference 15Brüggemann M et al. · 2003Total synthesis of (±)-didehydrostemofoline (asparagamine A) and (±)-isodidehydrostemofolineView study →}. It is a textbook demonstration of the aza-Cope–Mannich rearrangement Overman is known for.

Martin’s route (2012–13) approaches the same tricyclic core through a rhodium carbene that cyclises onto a proximal imine nitrogen to generate an azomethine ylide, which then undergoes spontaneous intramolecular dipolar cycloaddition — the whole core assembled from an acyclic precursor in a single cascade operation ^{17,18Reference 17Fang C et al. · 2012Enantioselective formal total syntheses of didehydrostemofoline and isodidehydrostemofoline through a catalytic dipolar cycloaddition cascadeView study →Reference 18Shanahan CS et al. · 2013Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution, development and application of a catalytic dipolar cycloaddition cascadeView study →}.

From Cage Alkaloid to Crop Protection

The most consequential downstream product of this chemistry is not a drug. Bayer’s flupyradifurone, launched as the first butenolide insecticide, came out of a discovery programme built around the butenolide scaffold of stemofoline; it acts reversibly as an agonist at insect nicotinic acetylcholine receptors, is structurally distinct from the neonicotinoids, and is not metabolised by CYP6CM1, the P450 behind metabolic neonicotinoid resistance in whiteflies ^{23Reference 23Nauen R et al. · 2015Flupyradifurone: a brief profile of a new butenolide insecticideView study →}. The natural product that put that scaffold on the map — and the more toxic of the pair in every side-by-side insect assay ^{5,6Reference 5Jiwajinda S et al. · 2001Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsaeView study →Reference 6Brem B et al. · 2002Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticidesView study →} — is this one.

There is no commercial preparation of asparagamine A. All material used in biology has come from Stemona root chromatography; all synthetic material has come from academic total or formal syntheses. Patents: not yet researched.

Toxicity & Safety

The honest verdict is not characterised in humans, and not a dietary molecule. The moderate grading reflects what it demonstrably is — a potent invertebrate neurotoxin from a pesticidal plant, with no mammalian isolate toxicology — rather than any demonstrated human harm.

Safety at a Glance

⚠️ Moderate toxicityDrug interactions

• No human adverse effect has been reported. No human has knowingly taken it, so this is an absence of data, not a safety record.
• Not cytotoxic to normal human cells in the one test available. Neither isomer harmed normal fibroblasts or peripheral blood mononuclear cells, and neither haemolysed human or rat erythrocytes ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}.
• It is a potent insecticide, more toxic to insects than pyrethrum in contact assays ^{6Reference 6Brem B et al. · 2002Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticidesView study →}. Selectivity for invertebrates is likely but has never been formally established for this molecule.
• Orally bioavailable in rats. Unlike most large plant molecules it does reach plasma quickly ^{14Reference 14Arlee N et al. · 2024AnimalLC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administrationView study →}, so an isolate exposure would be a real systemic exposure.
• P-glycoprotein inhibition is a drug-interaction mechanism. Functional P-gp blockade raises exposure to the many drugs that transporter exports ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}.
• The extract’s rodent LD₅₀ is around 500 mg/kg. For standardised S. collinsiae root extract, 300 mg/kg was non-toxic and 2,000 mg/kg was fatal in Wistar rats ^{13Reference 13Arlee N et al. · 2024Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profilesView study →} — an extract figure, not an isolate figure.
• No reproductive or developmental data exist. The one reproductive-sounding result in the whole literature is the unreplicated 1995 anti-oxytocin note ^{2Reference 2Sekine T et al. · 1995Structure and relative stereochemistry of a new polycyclic alkaloid, asparagamine A, showing anti-oxytocin activity, isolated from Asparagus racemosusView study →}, which is not a safety finding in either direction.
• Product substitution is the real-world risk. Stemona tubers have been sold as shatavari ^{3,4Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →} — the practical hazard is buying the wrong plant, not this molecule’s own toxicity.

Full Safety & Interactions Detail

No toxicology study has ever been performed on isolated asparagamine A in a mammal. What exists is bracketed on one side by invertebrate data — high contact and feeding toxicity to lepidopteran larvae, exceeding a commercial pyrethrum extract ^{6Reference 6Brem B et al. · 2002Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticidesView study →}, and an Aedes larval LC₅₀ of 2.44 µM ^{11Reference 11Chalom S et al. · 2021Cytotoxic and larvicidal activities of Stemona alkaloids from the aerial parts and roots of Stemona curtisii Hook.fView study →} — and on the other by a single mammalian-cell safety panel in which neither geometric isomer was cytotoxic to normal human fibroblasts or PBMCs and neither caused haemolysis ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}. Between those two poles there is nothing: no acute oral study of the isolate, no genotoxicity, no repeat-dose work, no reproductive study.

The extract-level toxicity data give a rough outer bound. In Wistar rats, standardised ethanolic S. collinsiae root extract was fatal at 2,000 mg/kg, non-toxic at 300 mg/kg, and assigned a GHS LD₅₀ of 500 mg/kg ^{13Reference 13Arlee N et al. · 2024Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profilesView study →} — but that extract is a mixture, and the contribution of any single alkaloid to that figure is unknown.

The interaction to take seriously is P-glycoprotein. Both isomers inhibit P-gp function in resistant leukaemia cells without changing its expression ^{12Reference 12Umsumarng S et al. · 2017Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationshipsView study →}.

P-gp governs the absorption and biliary/renal export of a long list of drugs — digoxin, many kinase inhibitors, several immunosuppressants, some anticoagulants and antiretrovirals — so functional inhibition is a plausible route to raised drug levels. Nothing here has been tested in vivo, and this concerns the isolate rather than any product a person would encounter.

Finally, the safety question most likely to matter in practice is botanical identity. The reason this molecule was ever associated with a women’s tonic is that Stemona root has been substituted for shatavari in trade ^{3,4Reference 3Kumeta Y et al. · 2013Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosusView study →Reference 4Seger C et al. · 2004Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formationView study →}. Stemona is a traditional pesticide and antitussive plant with its own alkaloid profile and its own toxicology — a shatavari product that contains asparagamine A is, by definition, not shatavari.

Dosage

There is no dose. Asparagamine A has never been given to a human as an isolate or a defined preparation, and there is no rationale on which to construct one. Every quantitative figure in this article is an insect LC₅₀, a cell-line accumulation assay, a rat plasma concentration, or an extract LD₅₀.

Where it appears in the real world it does so as a standardisation marker for Stemona collinsiae root extract in pesticide and anthelmintic development ^{9,13,14Reference 9Kongkiatpaiboon S · 2012HPLC quantitative analysis of insecticidal didehydrostemofoline and stemofoline in Stemona collinsiae root extractsView study →Reference 13Arlee N et al. · 2024Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profilesView study →Reference 14Arlee N et al. · 2024AnimalLC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administrationView study →} — a number on a certificate of analysis, not a dose. Nothing here is a recommendation.

References

1. Sekine T, Fukasawa N, Kashiwagi Y, Ruangrungsi N, Murakoshi I (1994). Structure of asparagamine A, a novel polycyclic alkaloid from Asparagus racemosus. Chemical and Pharmaceutical Bulletin 42(6):1360–1362. https://doi.org/10.1248/cpb.42.1360
2. Sekine T, Ikegami F, Fukasawa N, Kashiwagi Y, Aizawa T, Fujii Y, Ruangrungsi N, Murakoshi I (1995). Structure and relative stereochemistry of a new polycyclic alkaloid, asparagamine A, showing anti-oxytocin activity, isolated from Asparagus racemosus. Journal of the Chemical Society, Perkin Transactions 1 391–393. https://doi.org/10.1039/p19950000391
3. Kumeta Y, Maruyama T, Wakana D, Kamakura H, Goda Y (2013). Chemical analysis reveals the botanical origin of shatavari products and confirms the absence of alkaloid asparagamine A in Asparagus racemosus. Journal of Natural Medicines. https://pubmed.ncbi.nlm.nih.gov/22529051/
4. Seger C, Mereiter K, Kaltenegger E, Pacher T, Greger H, Hofer O (2004). Two pyrrolo[1,2-a]azepine type alkaloids from Stemona collinsae Craib: structure elucidations, relationship to asparagamine A, and a new biogenetic concept of their formation. Chemistry & Biodiversity. https://pubmed.ncbi.nlm.nih.gov/17191845/
5. Jiwajinda S, Hirai N, Watanabe K, Santisopasri V, Chuengsamarnyart N, Koshimizu K, Ohigashi H (2001). Occurrence of the insecticidal 16,17-didehydro-16(E)-stemofoline in Stemona collinsae. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/11314954/
6. Brem B, Seger C, Pacher T, Hofer O, Vajrodaya S, Greger H (2002). Feeding deterrence and contact toxicity of Stemona alkaloids — a source of potent natural insecticides. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/12381121/
7. Schinnerl J, Brem B, But PP, Vajrodaya S, Hofer O, Greger H (2007). Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona species. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/17449078/
8. Greger H (2006). Structural relationships, distribution and biological activities of Stemona alkaloids. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/16491444/
9. Kongkiatpaiboon S, Gritsanapan W (2012). HPLC quantitative analysis of insecticidal didehydrostemofoline and stemofoline in Stemona collinsiae root extracts. Phytochemical Analysis. https://pubmed.ncbi.nlm.nih.gov/22396063/
10. Kongkiatpaiboon S, Schinnerl J, Felsinger S, Keeratinijakal V, Vajrodaya S, Gritsanapan W, Brecker L, Greger H (2011). Structural relationships of Stemona alkaloids: assessment of species-specific accumulation trends for exploiting their biological activities. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/21902195/
11. Chalom S, Panyakaew J, Phaya M, Pyne SG, Mungkornasawakul P (2021). Cytotoxic and larvicidal activities of Stemona alkaloids from the aerial parts and roots of Stemona curtisii Hook.f. Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/31899956/
12. Umsumarng S, Pitchakarn P, Yodkeeree S, Punfa W, Mapoung S, Ramli RA, Pyne SG, Limtrakul P (2017). Modulation of P-glycoprotein by Stemona alkaloids in human multidrug resistance leukemic cells and structural relationships. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/28899501/
13. Arlee N, Ampawong S, Kongkiatpaiboon S, Limpanont Y, Arunrungvichian K, Thepouyporn A, Pakdee W, Thaenkham U (2024). Assessing the efficacy of Stemona collinsiae roots extract against third-stage larvae of Gnathostoma spinigerum and its safety profiles. Heliyon. https://pubmed.ncbi.nlm.nih.gov/39397923/
14. Arlee N, Ampawong S, Limpanont Y, Arunrungvichian K, Kongkiatpaiboon S, Thaenkham U (2024). LC-MS/MS analysis of didehydrostemofoline from Stemona collinsiae roots extracts in rats plasma and pharmacokinetics profile after oral administration. Fitoterapia. https://pubmed.ncbi.nlm.nih.gov/38823598/
15. Brüggemann M, McDonald AI, Overman LE, Rosen MD, Schwink L, Scott JP (2003). Total synthesis of (±)-didehydrostemofoline (asparagamine A) and (±)-isodidehydrostemofoline. Journal of the American Chemical Society 125(50):15284–15285. https://pubmed.ncbi.nlm.nih.gov/14664560/
16. Epperson MT, Gin DY (2002). Enantiospecific synthesis of the bridged pyrrolizidine core of asparagamine A: dipolar cycloadditions of azomethine ylides derived from the sulfonylation of vinylogous amides. Angewandte Chemie International Edition. https://pubmed.ncbi.nlm.nih.gov/19750714/
17. Fang C, Shanahan CS, Paull DH, Martin SF (2012). Enantioselective formal total syntheses of didehydrostemofoline and isodidehydrostemofoline through a catalytic dipolar cycloaddition cascade. Angewandte Chemie International Edition. https://pubmed.ncbi.nlm.nih.gov/22987285/
18. Shanahan CS, Fang C, Paull DH, Martin SF (2013). Asymmetric formal total synthesis of the stemofoline alkaloids: the evolution, development and application of a catalytic dipolar cycloaddition cascade. Tetrahedron. https://pubmed.ncbi.nlm.nih.gov/24072939/
19. Anderson BK, Livinghouse T (2015). Divergent stereocontrolled synthesis of the enantiopure tetracyclic cores of asparagamine A and stemofoline via an intramolecular 2-propylidine-1,3-(bis)silane bicyclization. The Journal of Organic Chemistry. https://pubmed.ncbi.nlm.nih.gov/26360508/
20. Wiboonpun N, Phuwapraisirisan P, Tip-pyang S (2004). Identification of antioxidant compound from Asparagus racemosus. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/15478181/
21. Wild Asparagus. In: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006 (record updated July 2026). https://pubmed.ncbi.nlm.nih.gov/30000872/
22. Arya PK, Barik K, Kumar A (2026). Targeting spermidine synthase in Leishmania donovani: molecular docking and molecular dynamics simulation-based evaluation of Indian medicinal plant phytochemicals. In Silico Pharmacology. https://pubmed.ncbi.nlm.nih.gov/41459411/
23. Nauen R, Jeschke P, Velten R, Beck ME, Ebbinghaus-Kintscher U, Thielert W, Wölfel K, Haas M, Kunz K, Raupach G (2015). Flupyradifurone: a brief profile of a new butenolide insecticide. Pest Management Science. https://pubmed.ncbi.nlm.nih.gov/25351824/
24. Liu Y, Shen Y, Teng L, Yang L, Cao K, Fu Q, Zhang J (2021). The traditional uses, phytochemistry, and pharmacology of Stemona species: a review. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/32726680/
25. Sastraruji K, Sastraruji T, Pyne SG, Ung AT, Jatisatienr A, Lie W (2010). Semisynthesis and acetylcholinesterase inhibitory activity of stemofoline alkaloids and analogues. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/20415428/

View all 25 references▾