Tribulusamide D

Tribulusamide D at a Glance

Tribulusamide D is a small phenolic amide from the fruit of Tribulus (Tribulus terrestris) — chemically, a molecule of caffeic acid joined through an amide bond to 2-amino-1-(4-hydroxyphenyl)ethanone. It is C₁₇H₁₅NO₅, molecular weight 313.3, and it was named in 2013 by a Korean group who found it alongside four previously known amides in the same extract ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}.

Two corrections frame the account, and both matter more than anything the molecule does.

It is not a saponin, and it is not a lignanamide. Tribulus is famous for its steroidal saponins — protodioscin and its relatives — and this molecule has nothing to do with them. It is also routinely filed as a “lignanamide” because tribulusamides A and B genuinely are lignanamides, and the shared name implies a shared class. They are not the same kind of thing: A and B are ~625–640 Da dimers built on a dihydrobenzofuran core with two nitrogen atoms; tribulusamide D is a 313 Da monomer with one. The class label here has been corrected accordingly, and the original paper agrees — its title is “Phenolic Amides from the Fruits of Tribulus terrestris” ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}.

Its whole literature is two papers from one laboratory. The 2013 isolation paper and a 2017 mechanistic follow-up, both from the same group in Suwon and Cheonan ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. Nobody else has isolated it, quantified it, replicated it, or tested it in an animal. PubChem holds the structure but registers no name for it. Everything below rests on that two-paper base, and the more interesting of the two findings is the one the follow-up paper left out.

It Is Not a Lignanamide — Fixing the Class

The Tribulus amides are a genuinely interesting little family, but they are not one class. Sorting them out is the single most useful thing to do.

Compound	Formula	MW	What it actually is
Tribulusamide A	C₃₆H₃₆N₂O₈	624.7	Lignanamide — a dihydrobenzofuran dimer of two cinnamic amide units ^{3Reference 3Li JX et al. · 1998AnimalTribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: indications of cytoprotective activity in murine hepatocyte cultureView study →}
Tribulusamide B	C₃₆H₃₄N₂O₉	638.7	Lignanamide — the same dimeric skeleton ^{3Reference 3Li JX et al. · 1998AnimalTribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: indications of cytoprotective activity in murine hepatocyte cultureView study →}
Tribulusamide C	—	—	A feruloyl amide with a pyrrolidine-2,5-dione unit, explicitly distinguished from the lignanamides ^{4Reference 4Zhang X et al. · 2012A new feruloyl amide derivative from the fruits of Tribulus terrestrisView study →}
Tribulusamide D	C₁₇H₁₅NO₅	313.3	Monomeric phenolic amide — one caffeoyl unit, one amine unit ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}
Terrestriamide	C₁₈H₁₇NO₅	327.3	The same skeleton as D, with a methoxyl where D carries a hydroxyl
N-trans-p-Caffeoyltyramine	C₁₇H₁₇NO₄	299.3	Caffeic acid + tyramine — the closest well-studied relative

The names run A, B, C, D in order of discovery, not in order of structure. Tribulusamide D’s actual nearest neighbour is terrestriamide, which was already known when D was described; the 2013 authors identified D precisely by noting that its NMR spectrum was “very similar” to terrestriamide’s, differing only in that the C-3 methoxyl of terrestriamide is a free hydroxyl in D ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. In other words, tribulusamide D is the caffeoyl version of a feruloyl compound — a demethylated analogue, the same relationship caffeic acid has to ferulic acid.

Practically, that puts it one bond away from N-trans-p-caffeoyltyramine, which has its own page here and which was isolated from the same extract ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. Both carry the same catechol-bearing caffeoyl head. They differ only in the amine tail: caffeoyltyramine ends in a 4-hydroxyphenethyl group, tribulusamide D ends in a 4-hydroxyphenacyl group — a ketone where the other has a methylene. That one carbonyl turns out to cost it most of its activity.

The Whole Literature: Two Papers, One Laboratory

A PubMed search for tribulusamide returns six records in total. Three of those involve Tribulus terrestris, and only one of the three is about tribulusamide D — the 2017 mechanism paper ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. The other two describe tribulusamides A and B (1998) and tribulusamide C (2012) ^{3,4Reference 3Li JX et al. · 1998AnimalTribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: indications of cytoprotective activity in murine hepatocyte cultureView study →Reference 4Zhang X et al. · 2012A new feruloyl amide derivative from the fruits of Tribulus terrestrisView study →}. The remaining three records concern tribulusamide A or B in unrelated contexts and never mention D.

The paper that actually named and characterised tribulusamide D — Hong et al., Bulletin of the Korean Chemical Society, 2013 — is not indexed in PubMed at all ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. That is the paper carrying the structure elucidation, the co-isolated compounds, and the comparative potency data, so a literature search that stops at PubMed will find only the follow-up and none of the context.

Both papers share authors (Hong SS, Ahn EK, Oh JS), the same institutions, and the same assay system. The same laboratory also published the companion paper on N-trans-p-caffeoyltyramine, in the same cell line, with a near-identical panel of readouts ^{8Reference 8Ko HJ et al. · 2015In vitroN-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells — in vitroView study →}. This is one research programme, not a converging literature.

There has been one independent re-investigation of the same material. In 2018 a group at Chungbuk National University isolated eleven phenolic amides from methanolic T. terrestris fruit extract — including a new cis-terrestriamide — and measured NO inhibition in the same RAW 264.7 model, reporting IC₅₀ values of 18.7–49.4 µM for seven of them ^{5Reference 5Kim HS et al. · 2018In vitroPhenolic amides from Tribulus terrestris and their inhibitory effects on nitric oxide production in RAW 264.7 cells — in vitroView study →}. That confirms the amide fraction is genuinely active and roughly reproduces the potency band of the 2013 series. It does not corroborate tribulusamide D specifically: the compound is not named in that report, and the IC₅₀ range quoted sits well below the 83.4 µM measured for D.

What It's Used For

One activity has ever been measured for this molecule: suppression of inflammatory mediators in a stimulated mouse macrophage line. There is nothing else — no antioxidant assay, no enzyme panel, no animal study, no human data.

It suppresses NO, PGE₂, COX-2 and cytokines in LPS-stimulated RAW 264.7 macrophages — at high micromolar concentrations.At 100 µM it cut nitric-oxide production by 77.6%, dose-dependently reduced iNOS and COX-2 at both mRNA and protein level, and lowered TNF-α, IL-6 and IL-10 ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

The upstream mechanism is p38 MAPK and NF-κB.Tribulusamide D blocked LPS-induced p38 phosphorylation and reduced NF-κB nuclear translocation, while leaving ERK and JNK untouched — a reasonably selective signature within the MAPK family ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

It was the weakest of the four active amides in its own founding paper.IC₅₀ for NO inhibition was 83.4 ± 0.8 µM, against 14.7 µM for N-trans-p-caffeoyltyramine, 38.6 µM for terrestriamide and 42.3 µM for N-trans-feruloyltyramine — all from the same extract, all in the same assay. The positive control L-NMMA came in at 25.3 µM ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. Tribulusamide D is roughly 5.7× weaker than its own co-isolate and 3.3× weaker than the reference inhibitor.

It also suppressed IL-10, an anti-inflammatory cytokine.Both this molecule and its caffeoyltyramine sibling reduced IL-10 alongside TNF-α and IL-6 ^{2,8Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →Reference 8Ko HJ et al. · 2015In vitroN-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells — in vitroView study →}. Broad flattening of cytokine output is a weaker claim than selective suppression of the inflammatory arm.

Nothing has been shown in a living organism.No animal experiment, no pharmacokinetics, no human exposure data of any kind.

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. There is exactly one row here because exactly one activity has ever been measured for this molecule, in one cell line, by one laboratory.

The 2013 screen measured NO inhibition in LPS-stimulated RAW264.7 cells for all five compounds isolated from T. terrestris fruit. Four were active. Tribulusamide D came last among them at IC₅₀ 83.4 ± 0.8 µM; N-trans-p-caffeoyltyramine was the standout at 14.7 ± 0.3 µM, with terrestriamide at 38.6 µM and N-trans-feruloyltyramine at 42.3 µM. Terrestribisamide was inactive (>100 µM). None was cytotoxic below 100 µM by MTT, so the inhibition was not a viability artefact ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}.

The 2017 follow-up took the weakest of those four and worked out its mechanism. Cells were pretreated for 1 h at 25, 50 and 100 µM, then stimulated with LPS at 0.5 µg/mL for 24 h. NO fell 77.6% at 100 µM — comparable to the L-NMMA control at the same concentration. iNOS and COX-2 dropped dose-dependently by RT-PCR, western blot and immunofluorescence; PGE₂ fell significantly at 100 µM, comparable to celecoxib at 5 µM; and TNF-α, IL-6 and IL-10 all declined, against a dexamethasone control at 25 µM. Upstream, the compound inhibited p38 MAPK phosphorylation and reduced NF-κB nuclear localisation, with no effect on ERK or JNK ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

Gap: every number is from a single immortalised mouse macrophage line, in a concentration window (25–100 µM) that straddles the compound’s own IC₅₀ of 83.4 µM. The comparisons that flatter it are against inhibitors used far below their own potency (celecoxib at 5 µM). There is no animal model, no oral dosing, no measurement of whether these concentrations are reachable in any tissue, and no independent replication. And within its own chemical series it is the least active member — so if a Tribulus preparation has an amide-driven anti-inflammatory effect, the evidence points at caffeoyltyramine and terrestriamide before it points here ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

Mechanisms

Target / pathway	Effect	Relevant to	Evidence tier
iNOS expression → NO production	dose-dependent suppression; IC₅₀ 83.4 µM, −77.6% at 100 µM	anti-inflammatory	in vitro, one cell line ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}
COX-2 expression → PGE₂	dose-dependent suppression at mRNA and protein level	anti-inflammatory	in vitro ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}
TNF-α, IL-6, IL-10	reduced at mRNA and protein level (including the anti-inflammatory IL-10)	anti-inflammatory	in vitro ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}
p38 MAPK phosphorylation	inhibited; ERK and JNK unaffected	upstream signalling	in vitro ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}
NF-κB nuclear translocation	reduced after 30 min LPS	upstream signalling	in vitro ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}

Pharmacokinetics

None exists. There is no absorption, distribution, metabolism or excretion data for tribulusamide D in any species, and no measurement of the compound in plasma or tissue after any route of administration.

What can be said is structural and inferential. At 313 Da with three free phenolic hydroxyls, one amide and one aryl ketone, it is a small, moderately polar molecule — physically far more plausible as an absorbable species than the 850–1,050 Da steroidal saponins that dominate the same plant. But phenolic amides of this type are subject to extensive phase II conjugation (glucuronidation and sulfation of the phenol groups) on first pass, and the catechol is additionally a substrate for COMT methylation — which would convert tribulusamide D into terrestriamide, its own O-methyl relative. None of that has been measured for this molecule; it is the class expectation, flagged as such.

The practical consequence is the important one. The activity above sits at 25–100 µM. Free plasma concentrations in that range are not something a trace amide in a herbal fruit preparation produces, and nobody has demonstrated otherwise.

Clinical Trials

None. There is no registered clinical study of tribulusamide D under any name, and no animal study either.

Completed	Planned	Terminated	Preclinical
—(none)	—	—	2in-vitro papers

Last checked: August 2026.

The Hepatoprotective Story Belongs to A and B, Not D

Tribulus’s amide fraction has a real hepatoprotective finding attached to it, and it is worth stating precisely who it belongs to — because it is easily and frequently mis-assigned to the whole “tribulusamide” series.

In 1998, Li and colleagues at Toyama isolated tribulusamides A and B from T. terrestris fruit, along with N-trans-feruloyltyramine, terrestriamide, N-trans-coumaroyltyramine and β-sitosterol. Added to primary cultured mouse hepatocytes, all six compounds — A and B especially — significantly prevented cell death induced by D-galactosamine plus TNF-α ^{3Reference 3Li JX et al. · 1998AnimalTribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: indications of cytoprotective activity in murine hepatocyte cultureView study →}. That is the origin of the phrase “hepatoprotective lignanamides,” and it applies to the two dimeric lignanamides described in that paper.

Tribulusamide D did not exist as a named compound until fifteen years later ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}, and it has never been tested in a hepatocyte model, or in any liver model. It shares a name prefix with the hepatoprotective compounds and nothing else. Any source that extends the 1998 finding to tribulusamide D is extrapolating across a class boundary.

That correction matters here for a second reason. The same herb supplies terrestrosin D, a spirostanol saponin implicated as a driver of hepatorenal toxicity. A page-level pairing of “the hepatoprotective tribulusamide” against “the hepatotoxic terrestrosin” would be a tidy story and is not one this evidence supports: the hepatoprotection belongs to A and B, and D has simply never been looked at.

Isolate vs. Plant

Unusually, the isolate/plant boundary is clean — every result for this molecule is on purified compound, because tribulusamide D only ever appears in the literature as a numbered line item in a bioassay-guided fractionation ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. There is no whole-extract study being passed off as a molecule result.

The problem runs the other way. Nothing here supports a claim about Tribulus terrestris as a herb. In its own founding paper it was the weakest of four active co-isolates ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}; in the follow-up it was the only compound tested, so no comparison was possible ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. Meanwhile the herb’s other cinnamic amides carry considerably stronger in-vitro pharmacology that has nothing to do with this molecule: N-trans-coumaroyltyramine inhibits α-glucosidase at IC₅₀ 0.42 µM by an unusual uncompetitive mechanism ^{6Reference 6Song YH et al. · 2016In vitroCinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition — in vitroView study →}, and a set of six Tribulus cinnamic amides inhibit SARS-CoV papain-like protease at 15.8–70.1 µM, with the authors confirming by HPLC and LC-DAD-ESI/MS that those amides are present in native fruit in high quantities ^{7Reference 7Song YH et al. · 2014In vitroPapain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits — in vitroView study →}. Tribulusamide D is not among them.

And all of that sits inside a much larger caveat: the human and clinical literature on Tribulus concerns standardised saponin extracts — protodioscin-based, marketed for sexual function — whose content varies enormously by geographic origin and plant part. None of that evidence involves the amide fraction at all.

Prevalence in Nature

Tribulusamide D has been reported from exactly one species and one tissue: the fruit of Tribulus terrestris ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. It has not been found in any other plant, and the compound carries no registered synonym in PubChem — the structure is indexed there (CID 162862002) with a systematic name only, which is what a molecule looks like when it has been described once and never picked up.

No concentration figure exists for it in any material. The only quantitative anchor is a purification yield: 17.3 mg of pure compound from 10 kg of air-dried fruit in the 2017 isolation, roughly 0.0002% w/w ^{2Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}. That is a floor, not a content figure — column losses across an ethanol extraction, three solvent partitions, silica chromatography and a Sephadex step are large and unmeasured. It is nonetheless enough to establish the order of magnitude: this is a trace constituent, present at a small fraction of a percent, in a plant whose marketed actives are measured in whole percentage points.

Its close relatives are more widely distributed. N-trans-feruloyltyramine and N-trans-p-caffeoyltyramine occur across many families — hemp seed, goji root bark, various Solanaceae — and it would be unsurprising if tribulusamide D turned up elsewhere once anyone looked. Nobody has.

Discovery & Synthesis

Tribulusamide D was described in 2013 by Seong Su Hong, Wonsik Jeong and co-workers at the Natural Products Research Institute of the Gyeonggi Institute of Science & Technology Promotion, working with the College of Pharmacy at Dankook University ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. It was compound 1 of five isolated from an aqueous-ethanolic extract of dried T. terrestris fruit by Sephadex LH-20, reversed-phase and silica gel chromatography — the others being terrestriamide, N-trans-caffeoyl tyramine, N-trans-feruloyl tyramine and terrestribisamide.

The structure was settled by HRESIMS at m/z 314.1017 [M+H]⁺ (calculated 314.1023 for C₁₇H₁₆NO₅, indicating C₁₇H₁₅NO₅ and 11 degrees of unsaturation), UV maxima at 219, 242, 290 and 319 nm characteristic of a 3,4-dioxygenated cinnamic acid, and IR bands for hydroxyl (3316 cm⁻¹) and amide (1653 cm⁻¹). The ¹H NMR showed the caffeoyl ABX system, a trans olefin pair at J = 16.1 Hz, a 1,4-disubstituted aromatic ring, a methylene at δ 4.65, an amide NH triplet and three hydroxyls; ¹³C placed a ketone at δ 193.9 and the amide carbonyl at δ 166.2. HMBC correlations tied the pieces together, giving (E)-3-(3,4-dihydroxyphenyl)-N-[2-(4-hydroxyphenyl)-2-oxoethyl]prop-2-enamide ^{1Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →}. The name follows tribulusamides A–C in sequence, not in structural kinship.

There is no total synthesis on record, and no commercial supply. The molecule would be a short synthesis if anyone wanted it — an amide coupling between caffeic acid and 2-amino-4′-hydroxyacetophenone — but no such route has been published, and all material described to date was obtained by chromatography from plant extract. Patents: not yet researched.

Toxicity & Safety

The honest verdict is not characterised. There has never been a toxicology study of tribulusamide D — no acute-toxicity work, no genotoxicity panel, no reproductive study, no animal experiment at all. The low grading reflects the exposure route (a trace phenolic amide in a long-consumed food and medicinal fruit) and the absence of any structural alert, not a demonstrated safety record.

Safety at a Glance

Low / no toxicity

No toxicity signal has been reported. No study has looked for one — those are different statements.
Not cytotoxic to macrophages up to 100 µM by MTT, in both papers that tested it ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.
The bound tyramine-type amine is not free tyramine. Locked into an amide, it does not carry a biogenic amine’s pressor or MAO liability.
No in-vivo data of any kind. No animal has received this compound. Systemic effects, metabolism and target-organ toxicity are all unknown.
No reproductive or developmental data exist. Nothing is known about pregnancy or breastfeeding at the molecular level; the herb Tribulus terrestris itself carries its own separate cautions, which is where that decision belongs.
It suppresses IL-10 as well as TNF-α and IL-6 ^{2,8Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →Reference 8Ko HJ et al. · 2015In vitroN-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells — in vitroView study →}. Broad cytokine suppression is not the same as targeted anti-inflammatory action, and the immunological consequence has not been examined.
No drug-interaction data. No CYP, transporter or protein-binding work has been done. The catechol group makes COMT and phase-II conjugation the obvious things to check first; nobody has.
Do not read Tribulus safety off it. The herb’s toxicology signals — including hepatorenal findings attributed to its spirostanol saponins — belong to different molecules entirely.

Dosage

There is no dose. Tribulusamide D has never been administered to a human being or an animal, and there is no dosing study to extrapolate from. The only numbers in its literature are in-vitro concentrations: 25, 50 and 100 µM in a macrophage culture, around an IC₅₀ of 83.4 µM ^{1,2Reference 1Hong SS et al. · 2013Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxideView study →Reference 2Lee HH et al. · 2017In vitroAnti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitroView study →}.

Real-world exposure comes only from Tribulus terrestris fruit preparations, where it is one trace amide among many — and where the plant, standardised to its saponins, is the thing actually being taken. Nothing here is a recommendation.

References

Hong SS, Jeong W, Kwon JG, Choi YH, Ahn EK, Ko HJ, Seo DW, Oh JS (2013). Phenolic amides from the fruits of Tribulus terrestris and their inhibitory effects on the production of nitric oxide. Bulletin of the Korean Chemical Society 34:3105–3108. https://doi.org/10.5012/bkcs.2013.34.10.3105
Lee HH, Ahn EK, Hong SS, Oh JS (2017). Anti-inflammatory effect of tribulusamide D isolated from Tribulus terrestris in lipopolysaccharide-stimulated RAW264.7 macrophages — in vitro. Molecular Medicine Reports. https://pubmed.ncbi.nlm.nih.gov/28849109/
Li JX, Shi Q, Xiong QB, Prasain JK, Tezuka Y, Hareyama T, Wang ZT, Tanaka K, Namba T, Kadota S (1998). Tribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: indications of cytoprotective activity in murine hepatocyte culture. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/9810268/
Zhang X, Wei N, Huang J, Tan Y, Jin D (2012). A new feruloyl amide derivative from the fruits of Tribulus terrestris. Natural Product Research. https://pubmed.ncbi.nlm.nih.gov/22149942/
Kim HS, Lee JW, Jang H, Le TPL, Kim JG, Lee MS, Hong JT, Lee MK, Hwang BY (2018). Phenolic amides from Tribulus terrestris and their inhibitory effects on nitric oxide production in RAW 264.7 cells — in vitro. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/29177586/
Song YH, Kim DW, Curtis-Long MJ, Park C, Son M, Kim JY, Yuk HJ, Lee KW, Park KH (2016). Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition — in vitro. European Journal of Medicinal Chemistry. https://pubmed.ncbi.nlm.nih.gov/26974386/
Song YH, Kim DW, Curtis-Long MJ, Yuk HJ, Wang Y, Zhuang N, Lee KH, Jeon KS, Park KH (2014). Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris fruits — in vitro. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/24882413/
Ko HJ, Ahn EK, Oh JS (2015). N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cells — in vitro. International Journal of Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/26239676/