Tiliroside

Tiliroside at a Glance

Tiliroside is an acylated flavonol glycoside — chemically kaempferol-3-O-β-D-(6”-O-p-coumaroyl)glucoside. It is a molecule of kaempferol carrying a sugar (glucose) at the 3-position, with that sugar further esterified by a molecule of p-coumaric acid. It is the signature flavonoid of linden (Tilia) flowers and a characteristic constituent of rosehips, strawberry and elder ^{1,10Reference 1Qiao W et al. · 2011Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinensisView study →Reference 10Herrera-Ruiz M et al. · 2008Flavonoids from Tilia americana with anxiolytic activity in plus-maze testView study →}.

Its marquee interest is metabolic. In obese-diabetic mice, tiliroside enhances fatty-acid oxidation in liver and skeletal muscle by activating adiponectin signalling, downstream AMPK and hepatic PPAR-α — improving insulin resistance and blood lipids even where it does not straightforwardly reduce body weight ^{3Reference 3Goto T et al. · 2012AnimalTiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic miceView study →}. A parallel literature reports anti-inflammatory, antioxidant/Nrf2-activating and hepatoprotective effects in cell and animal models ^{5,6,8,9Reference 5Sala A et al. · 2003Assessment of the anti-inflammatory activity and free radical scavenger activity of tilirosideView study →Reference 6Zhuang H et al. · 2021Tiliroside ameliorates ulcerative colitis by restoring the M1/M2 macrophage balance via the HIF-1α/glycolysis pathwayView study →Reference 8Velagapudi R et al. · 2018Activation of Nrf2 pathway contributes to neuroprotection by the dietary flavonoid tilirosideView study →Reference 9Cai F et al. · 2025A novel KEAP1 inhibitor, tiliroside, activates NRF2 to protect against acetaminophen-induced oxidative stress and acute liver injuryView study →}.

Two honest caveats frame all of it. First, the human evidence belongs to whole rosehip extract standardised to tiliroside, not to the purified molecule ^{4Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →}. Second, tiliroside is poorly absorbed as an intact glycoside — it is a substrate of intestinal efflux transport and crosses gut-cell models slowly ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →} — so in-vitro potency does not translate directly into oral effect.

An Acylated Kaempferol Glycoside

The point of this molecule — what separates it from plain kaempferol — is the acyl group. Most dietary kaempferol travels as simple glycosides (astragalin, nicotiflorin). Tiliroside adds a p-coumaroyl ester to the 6” position of the glucose, producing an acylated flavonol glycoside that is markedly more lipophilic than the parent aglycone or its plain glucoside ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}.

That extra lipophilicity is the compound-unique angle. Structure–activity work on the Rosa canina anti-obesity principle found that the coumaroyl acylation is required for the potent anti-adiposity effect: the intact trans-tiliroside outperformed kaempferol and non-acylated kaempferol glucosides in the same assay ^{2Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →}. So tiliroside is not simply a “kaempferol delivery form” — the p-coumaroyl ester carries activity of its own, and the two halves (kaempferol and p-coumaric acid) are also released separately once the molecule is hydrolysed in the gut ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}.

The trans (E) configuration of the coumaroyl double bond is the naturally dominant and pharmacologically studied form; the cis isomer can form on exposure to light.

What It's Used For

Tiliroside’s evidence is preclinical: isolated-molecule work in cell and rodent models, plus one human trial of the rosehip extract it marks. It reads most strongly on the metabolic axis, with converging anti-inflammatory and antioxidant mechanisms.

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 here is preclinical (or, for the metabolic row, human only via a standardised extract), so read the per-row basis.

01Metabolic / Anti-ObesityShaky42%Multiple mouse models (adiponectin/AMPK/PPAR-α, visceral fat, glucose) + one rosehip-extract human RCT ^{2,3,4Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →Reference 3Goto T et al. · 2012AnimalTiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic miceView study →Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →}

02Anti-InflammatoryShaky36%In-vitro + mouse colitis / acute-lung-injury (NLRP3, NF-κB, M1/M2) ^{5,6,7Reference 5Sala A et al. · 2003Assessment of the anti-inflammatory activity and free radical scavenger activity of tilirosideView study →Reference 6Zhuang H et al. · 2021Tiliroside ameliorates ulcerative colitis by restoring the M1/M2 macrophage balance via the HIF-1α/glycolysis pathwayView study →Reference 7Zhong C et al. · 2023AnimalTiliroside attenuates NLRP3 inflammasome activation in macrophages and protects against acute lung injury in miceView study →}

03Antioxidant / NeuroprotectiveShaky30%Free-radical scavenging + Nrf2/HO-1 activation, cell & animal ^{5,8Reference 5Sala A et al. · 2003Assessment of the anti-inflammatory activity and free radical scavenger activity of tilirosideView study →Reference 8Velagapudi R et al. · 2018Activation of Nrf2 pathway contributes to neuroprotection by the dietary flavonoid tilirosideView study →}

04HepatoprotectiveShaky26%KEAP1–NRF2 mechanism, paracetamol liver-injury mice ^{9Reference 9Cai F et al. · 2025A novel KEAP1 inhibitor, tiliroside, activates NRF2 to protect against acetaminophen-induced oxidative stress and acute liver injuryView study →}

05Anxiolytic (Tilia Constituent)Shaky18%One active flavonoid in an anxiolytic Tilia americana bract fraction ^{10Reference 10Herrera-Ruiz M et al. · 2008Flavonoids from Tilia americana with anxiolytic activity in plus-maze testView study →}

Mechanisms

The unifying thread is a small set of master switches — adiponectin/AMPK for metabolism and KEAP1/Nrf2 for cytoprotection — rather than one receptor. The p-coumaroyl acylation, and the molecule’s lipophilicity, appear to matter for engaging them ^{2,3,9Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →Reference 3Goto T et al. · 2012AnimalTiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic miceView study →Reference 9Cai F et al. · 2025A novel KEAP1 inhibitor, tiliroside, activates NRF2 to protect against acetaminophen-induced oxidative stress and acute liver injuryView study →}.

Pharmacokinetics

Tiliroside’s Achilles heel is absorption. In the Caco-2 small-intestine model, intact trans-tiliroside permeated slowly (Papp ≈ 0.6 × 10⁻⁶ cm/s) — several-fold below kaempferol and dramatically below free p-coumaric acid (≈ 23 × 10⁻⁶ cm/s) — and its uptake was limited by the efflux transporter MRP2: MRP2 inhibitors (or co-incubation with kaempferol) raised transfer three-to-five-fold ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}. Only limited metabolism (two mono-glucuronides) occurred at the gut wall. Consistently, after oral dosing of a tiliroside-standardised Tilia fraction, intact tiliroside and its aglycone fragments were not detected in plasma over 24 h — the circulating species were biotransformation products, implying gut-microbial hydrolysis to kaempferol and p-coumaric acid before absorption ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}. No validated human bioavailability or half-life figure exists. This poor, efflux-limited oral exposure is the single biggest caveat on every in-vitro potency claim above.

Clinical Trials

There is no registered trial of isolated tiliroside. The nearest human evidence is a randomised, double-blind, placebo-controlled trial of a rosehip extract standardised to tiliroside (100 mg/day, 12 weeks), which significantly reduced abdominal visceral fat and body weight in pre-obese adults — an extract result attributed to, but not isolating, the molecule ^{4Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

The evidence is unusually isolate-heavy at the bench and extract-only in humans. Most mechanistic and in-vivo work uses purified tiliroside — but crucially, tiliroside isolated from plants other than the ones people drink: Rosa canina ^{2Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →}, Potentilla chinensis ^{1Reference 1Qiao W et al. · 2011Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinensisView study →}, Edgeworthia and Helichrysum. Those studies establish what the molecule does, not what linden-flower tea does. The only human trials, meanwhile, run the opposite way: they test whole rosehip extract standardised to tiliroside content ^{4Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →}, so the clinical anti-obesity signal is an extract effect in which tiliroside is the marker and presumed driver rather than the demonstrated sole cause. For linden (Tilia) specifically, tiliroside is a genuine marker flavonoid and a contributor to an anxiolytic bract fraction ^{10Reference 10Herrera-Ruiz M et al. · 2008Flavonoids from Tilia americana with anxiolytic activity in plus-maze testView study →}, but no isolated-tiliroside human data exist for any linden indication. Read across all of it, the transferability caveat cuts both ways — plant results can’t be pinned on the molecule, and the molecule’s rodent results can’t be pinned on any one plant.

Prevalence in Nature

Tiliroside is a widespread but usually minor flavonoid of the Rosaceae, Malvaceae and related families. It is the signature flavonoid of linden (Tilia) flowers, bracts and inflorescences, where it co-occurs with quercetin, kaempferol and their glycosides ^{10Reference 10Herrera-Ruiz M et al. · 2008Flavonoids from Tilia americana with anxiolytic activity in plus-maze testView study →}. It is a characteristic constituent of rosehip (Rosa canina) fruit and seed — the source exploited in the anti-obesity work ^{2,4Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →} — and is reported in strawberry (Fragaria), elder (Sambucus nigra), and various cinquefoils (Potentilla spp.) ^{1Reference 1Qiao W et al. · 2011Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinensisView study →}. Beyond the common edibles it turns up in Edgeworthia, Helichrysum, Pfaffia townsendii (a suma relative) and many other genera.

Source	Botanical	Part
Linden Flower	Tilia spp.	flower / bract / inflorescence
Rosehip	Rosa canina	fruit, seed
Strawberry	Fragaria spp.	fruit
Elder	Sambucus nigra	flower / fruit
Cinquefoil	Potentilla chinensis	aerial parts

Quantitatively, tiliroside is almost always a minor glycoside fraction rather than a bulk constituent, and consistent concentration figures are scarce — reported amounts vary widely with species, provenance, plant part and drying, and are rarely expressed on a comparable dry-weight basis ^{10Reference 10Herrera-Ruiz M et al. · 2008Flavonoids from Tilia americana with anxiolytic activity in plus-maze testView study →}. Because no reliably comparable percentages are available, no Content-by-Source chart is shown here; supplying those figures is a standing gap.

Discovery & Synthesis

Tiliroside takes its name from linden — the genus Tilia — of which it is the characteristic marker flavonoid. It has long been known to natural-product chemistry as an acylated kaempferol glycoside, but a clean “first isolated by X in year Y” record is not well documented in the accessible literature, and none is asserted one. Structurally it was resolved as kaempferol-3-O-β-D-(6”-O-p-coumaroyl)glucoside, with the naturally dominant, bioactive form being the trans (E) coumaroyl isomer ^{2Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →}.

Today tiliroside for research is obtained overwhelmingly by extraction and chromatographic isolation from plant material — commonly rosehip, Tilia, Potentilla or Helichrysum — rather than by total synthesis; it is a specialised reference/research compound, not a bulk-manufactured ingredient. In principle it is accessible synthetically by selective 6”-O-p-coumaroylation of a kaempferol-3-glucoside, but no dominant commercial synthetic route is documented here.

Patents: not yet researched.

Toxicity & Safety

Tiliroside carries a low toxicity flag. It is a dietary flavonoid — a normal constituent of foods and traditional infusions such as linden tea, rosehips and strawberry — and no specific human toxicity signal is associated with ordinary dietary exposure. Its poor oral absorption as an intact glycoside further limits systemic exposure ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}.

The important honesty is that its safety in isolation, at pharmacological doses, has not been formally characterised — there is no dedicated human safety dataset, no repeat-dose toxicology package summarised here, and no interaction study. Because tiliroside is hydrolysed toward kaempferol and p-coumaric acid before absorption ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}, class considerations for those fragments (e.g. kaempferol’s high-dose in-vitro caveats) are the more relevant lens than the intact glycoside.

Safety at a Glance

✅ Low / no toxicity

• Low-toxicity dietary flavonoid. Long-standing food/herbal-tea exposure (linden, rosehip, strawberry) with no established toxicity signal at dietary levels.
• Poor oral absorption limits systemic dose. The intact glycoside is efflux-limited and crosses the gut slowly, capping exposure.
• Isolate safety not formally established. No dedicated human toxicology, repeat-dose or drug-interaction data for the purified molecule at pharmacological doses.
• Reproductive/developmental data absent. No isolate reproductive-toxicity dataset; any pregnancy/lactation decision belongs to the specific herb or product, not this molecule page.

Dosage

There is no established human dose of isolated tiliroside for any use. The preclinical anti-obesity and metabolic effects were produced in rodents at roughly 0.4–10 mg/kg/day by mouth ^{1,2,3Reference 1Qiao W et al. · 2011Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinensisView study →Reference 2Ninomiya K et al. · 2007Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tilirosideView study →Reference 3Goto T et al. · 2012AnimalTiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic miceView study →}. The only human dosing is indirect: a rosehip extract standardised to tiliroside at 100 mg/day for 12 weeks in the visceral-fat trial ^{4Reference 4Nagatomo A et al. · 2015RCTDaily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trialView study →} — a whole-extract dose, not a purified-molecule one.

Given poor oral bioavailability of the intact glycoside ^{11Reference 11Luo Z et al. · 2015Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestineView study →}, these figures do not translate cleanly to a human isolate dose. These are doses studied in research and are not a personal recommendation.

References

1. Qiao W, et al. (2011). Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinensis. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/21463674/
2. Ninomiya K, et al. (2007). Potent anti-obese principle from Rosa canina: structural requirements and mode of action of trans-tiliroside. Bioorganic & Medicinal Chemistry Letters. https://pubmed.ncbi.nlm.nih.gov/17400451/
3. Goto T, et al. (2012). Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice. The Journal of Nutritional Biochemistry. https://pubmed.ncbi.nlm.nih.gov/21889885/
4. Nagatomo A, et al. (2015). Daily intake of rosehip extract decreases abdominal visceral fat in preobese subjects: a randomized, double-blind, placebo-controlled clinical trial. Diabetes, Metabolic Syndrome and Obesity. https://pubmed.ncbi.nlm.nih.gov/25834460/
5. Sala A, et al. (2003). Assessment of the anti-inflammatory activity and free radical scavenger activity of tiliroside. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/12568916/
6. Zhuang H, et al. (2021). Tiliroside ameliorates ulcerative colitis by restoring the M1/M2 macrophage balance via the HIF-1α/glycolysis pathway. Frontiers in Immunology. https://pubmed.ncbi.nlm.nih.gov/33868286/
7. Zhong C, et al. (2023). Tiliroside attenuates NLRP3 inflammasome activation in macrophages and protects against acute lung injury in mice. Molecules. https://pubmed.ncbi.nlm.nih.gov/38005247/
8. Velagapudi R, et al. (2018). Activation of Nrf2 pathway contributes to neuroprotection by the dietary flavonoid tiliroside. Molecular Neurobiology. https://pubmed.ncbi.nlm.nih.gov/29508282/
9. Cai F, et al. (2025). A novel KEAP1 inhibitor, tiliroside, activates NRF2 to protect against acetaminophen-induced oxidative stress and acute liver injury. Hepatology Communications. https://pubmed.ncbi.nlm.nih.gov/40008899/
10. Herrera-Ruiz M, et al. (2008). Flavonoids from Tilia americana with anxiolytic activity in plus-maze test. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/18539420/
11. Luo Z, et al. (2015). Transport of trans-tiliroside (kaempferol-3-β-D-(6”-p-coumaroyl-glucopyranoside) and related flavonoids across Caco-2 cells, as a model of absorption and metabolism in the small intestine. Xenobiotica. https://pubmed.ncbi.nlm.nih.gov/25761590/

View all 11 references▾