N-trans-p-Caffeoyltyramine

N-trans-p-Caffeoyltyramine at a Glance

N-trans-p-caffeoyltyramine is a phenolic amide — more precisely a hydroxycinnamic acid amide (phenolamide), formed by joining caffeic acid to the biogenic amine tyramine through an amide bond. Structurally it is caffeic acid’s catechol-bearing cinnamoyl unit capped onto tyramine’s 4-hydroxyphenethylamine, with the double bond in the trans (E) configuration — hence the name. It belongs to the same phenylpropanoid family the herb pages file it under, and is best read as a conjugate of two simpler molecules that each have their own monograph here.

It is a genuinely minor, widely scattered plant constituent. It appears in Tribulus terrestris (where this site meets it, as one of the herb’s anti-inflammatory amides), in hemp/Cannabis seed, in the root bark of goji (Lycium) — the traditional Chinese material cortex Lycii / di gu pi — and across various Solanaceae and other families ^{1,4Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →Reference 4Han SH et al. · 2002A new phenolic amide from Lycium chinense MillerView study →}. In none of these is it usually a headline compound; it is a trace-to-minor amide riding alongside larger constituents.

Its pharmacology is entirely preclinical — in-vitro and rodent only, no human trials — but it clusters into two coherent threads. The older, best-documented one is anti-inflammatory / antioxidant activity (suppressing NF-κB-driven inflammatory mediators in stimulated macrophages, and protecting cells from oxidative stress) ^{1,2Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →}. The newer and more striking one is a hepatic-lipid story: N-trans-p-caffeoyltyramine was identified as a potent HNF4α agonist that reverses fatty-liver (steatosis) storage in mice by switching on lipophagy ^{3Reference 3Lee SH et al. · 2021Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonistView study →}. Both are interesting; neither has been tested in people.

Classification — A Caffeic Acid–Tyramine Amide

The clearest way to place this molecule is as a two-part conjugate:

• The acid half — caffeic acid. A hydroxycinnamic (phenylpropanoid) acid carrying a catechol (3,4-dihydroxy) group. This is the redox-active, radical-scavenging end, and the reason the amide shows antioxidant behaviour at all.
• The amine half — tyramine. A 4-hydroxyphenethylamine (a decarboxylated tyrosine). In the free state tyramine is a vasoactive, MAO-sensitive biogenic amine; locked into an amide it is not free tyramine and does not carry tyramine’s pressor/“cheese-reaction” liability.

Joining them through the amide bond gives a hydroxycinnamic acid amide (HCAA / phenolamide) — a large plant class that also includes the feruloyl analogue (N-trans-feruloyltyramine) and the p-coumaroyl analogue, which frequently co-occur with it. On this site it sits in the phenylpropanoid subgroup of the phenolics, matching the classification used on the Tribulus page (Phenylpropanoid → phenolics · phenylpropanoids). (A sibling Tribulus amide, tribulusamide D, is referenced in the same context but does not yet have its own page here.)

What It's Used For

The evidence base is a modest preclinical scatter — a handful of cell and rodent studies on the isolate — organised around two themes: an older anti-inflammatory/antioxidant thread, and a newer, higher-profile hepatic-lipid/HNF4α thread. There is no human 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. Every row rests on isolate cell or rodent work with no human trials, so scores stay low by design; read the per-row basis.

01Anti-inflammatoryShaky38%One macrophage study: NO/PGE₂↓, iNOS/COX-2↓, cytokines↓ via NF-κB ^{1Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →}

02Antioxidant / NeuroprotectiveShaky32%One PC12 H₂O₂ study: SOD/CAT/GSH↑, MDA/ROS↓ ^{2Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →}

03Hepatic Lipid / Anti-Steatosis (HNF4α)Shaky34%HNF4α-agonist mechanism + diet-induced-obese mouse steatosis reversal ^{3Reference 3Lee SH et al. · 2021Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonistView study →}

Mechanisms

The load-bearing threads are NF-κB-mediated anti-inflammatory action and the HNF4α–lipophagy hepatic-lipid mechanism. The antioxidant behaviour is the expected contribution of the caffeic-acid catechol half and underpins the cytoprotective signal.

Pharmacokinetics

The human pharmacokinetics of N-trans-p-caffeoyltyramine are uncharacterised — no Cmax, half-life or oral-bioavailability data for the isolate. What can be said is structural: it is a moderately lipophilic phenolic amide, and as an amide it is a plausible substrate for esterase/amidase hydrolysis that would liberate caffeic acid and tyramine, each with its own disposition (caffeic acid heavily conjugated and rapidly cleared; free tyramine subject to MAO). The mouse anti-steatosis work dosed the compound orally and saw hepatic effects, implying meaningful oral exposure to liver tissue in rodents ^{3Reference 3Lee SH et al. · 2021Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonistView study →}, but this has not been translated to human ADME. Robust pharmacokinetic characterisation is a clear gap.

Clinical Trials

There are no clinical trials of N-trans-p-caffeoyltyramine. The entire evidence base is in-vitro and rodent work on the isolate; there is no established human use.

Last checked: July 2026.

Isolate vs. Plant Studies

The split is clean: every result is on the isolated molecule — from Tribulus into macrophages ^{1Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →}, from goji root bark onto PC12 cells ^{2Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →}, and as a screened HNF4α agonist in mice ^{3Reference 3Lee SH et al. · 2021Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonistView study →}. As an isolate-mechanism base that is a modest strength; as human evidence it is silent.

In its source plants, N-trans-p-caffeoyltyramine is consistently a minor, co-acting amide. In Tribulus terrestris it is one of several anti-inflammatory constituents, so the herb’s activity cannot be pinned to this amide alone. In goji root bark (cortex Lycii) it sits among a family of phenolic amides (the caffeoyl-, feruloyl-, coumaroyl-tyramines and their dihydro forms) that share antioxidant/anti-inflammatory behaviour ^{1,2,4Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →Reference 4Han SH et al. · 2002A new phenolic amide from Lycium chinense MillerView study →}. The correct framing: modest isolate mechanism + no human data + a minor-constituent role in every plant it comes from.

Its Role in Plants

Hydroxycinnamic acid amides like N-trans-p-caffeoyltyramine are part of a plant’s defence and structural phenolamide chemistry. They are built by amide-forming enzymes that couple hydroxycinnamoyl-CoA units (from the phenylpropanoid pathway) to amines such as tyramine, and they accumulate in bark, roots, seeds and wound/pathogen-challenged tissue, where they contribute to antioxidant defence, pathogen resistance and cell-wall cross-linking. That biology explains where the compound is found: concentrated in protective tissues like goji root bark and seed coats (hemp seed), and induced in stressed tissue. These are plant-biochemistry roles and should not be read as human pharmacology.

Prevalence in Nature

N-trans-p-caffeoyltyramine is widely but thinly distributed — a recurring minor amide rather than a signature compound of any one plant. It is reported in Tribulus terrestris, in hemp/Cannabis seed, in the root bark of goji (Lycium chinense / Lycium) where it is a characteristic cortex Lycii phenolamide, and across scattered Solanaceae, Annonaceae and other families ^{1,2,4Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →Reference 4Han SH et al. · 2002A new phenolic amide from Lycium chinense MillerView study →}. Quantitative levels are rarely published, and where they are it is a trace-to-minor constituent.

Major Natural Sources

Source	Plant part	Notes
Tribulus (Tribulus terrestris)	aerial parts / fruit	anti-inflammatory amide; source for the RAW 264.7 study 1Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →
Goji root bark (Lycium chinense, cortex Lycii)	root bark	characteristic phenolic amide; source for antioxidant/PC12 work 2,4Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →Reference 4Han SH et al. · 2002A new phenolic amide from Lycium chinense MillerView study →
Hemp seed (Cannabis sativa)	seed / seed coat	one of the seed’s phenolamides; minor

Levels are largely unquantified in the sources reviewed here; the occurrences are qualitative and the missing numbers are tracked for a later pass.

Toxicity & Safety

N-trans-p-caffeoyltyramine carries a low flag on the available (preclinical) evidence. In the published work it appears as a protective agent — anti-inflammatory, antioxidant and anti-steatotic ^{1,2,3Reference 1Ko HJ et al. · 2015N-trans-ρ-caffeoyl tyramine isolated from Tribulus terrestris exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 cellsView study →Reference 2Olatunji OJ et al. · 2017Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stressView study →Reference 3Lee SH et al. · 2021Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonistView study →} — not a toxicant, and it is consumed at trace levels in foods such as hemp seed and in traditional goji-root-bark preparations. Importantly, although the molecule contains a tyramine unit, that tyramine is bound in an amide and is not free, so the amide does not carry free tyramine’s pressor / MAO-interaction (“cheese reaction”) liability at intact-molecule level.

The honest limits are the usual ones for a compound with no human data: there are no dedicated repeat-dose, genotoxicity or reproductive-toxicity studies of the pure isolate, and no human drug-interaction studies. A theoretical consideration is that amide hydrolysis could in principle release tyramine and caffeic acid, but no toxicity has been attributed to this in practice. Its HNF4α and anti-inflammatory activities are pharmacologically interesting but have only been shown at research doses in animals and cells.

Safety at a Glance

✅ Low / no toxicity

• Reads as protective, not toxic, in preclinical work. Anti-inflammatory, antioxidant and anti-steatotic effects in cells and mice — no toxicity signal at the doses studied.
• Bound tyramine, not free. The tyramine unit is locked in an amide, so the intact molecule does not carry free tyramine’s pressor / MAO-interaction risk.
• No human data at all. No clinical trials, and no characterised repeat-dose / genotoxicity package for the pure isolate.
• Interactions untested. Drug-interaction potential (including any from hydrolysis to caffeic acid + tyramine) is theoretical and unstudied.

Dosage

There is no established or recommended human dose for isolated N-trans-p-caffeoyltyramine. The only quantitative figures are preclinical research doses, not convertible to human self-dosing:

Human exposure is dietary and low — trace amounts in hemp seed and in traditional goji-root-bark (cortex Lycii) preparations. These are doses studied in research and are not a personal recommendation.

References

1. 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. International Journal of Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/26239676/
2. Olatunji OJ, Chen H, Zhou Y (2017). Neuroprotective effect of trans-N-caffeoyltyramine from Lycium chinense against H₂O₂ induced cytotoxicity in PC12 cells by attenuating oxidative stress. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/28715870/
3. Lee SH, Veeriah V, Levine F (2021). Liver fat storage is controlled by HNF4α through induction of lipophagy and is reversed by a potent HNF4α agonist. Cell Death & Disease. https://pubmed.ncbi.nlm.nih.gov/34117215/
4. Han SH, Lee HH, Lee IS, Moon YH, Woo ER (2002). A new phenolic amide from Lycium chinense Miller. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/12214850/
5. Lee HH, Ahn EK, Hong SS, Oh JS (2017). Anti-inflammatory effect of tribulusamide D from Tribulus terrestris in LPS-stimulated RAW 264.7 macrophages. Molecular Medicine Reports. https://pubmed.ncbi.nlm.nih.gov/28849109/