6-Demethoxycapillarisin

6-Demethoxycapillarisin at a Glance

6-Demethoxycapillarisin is a 2-phenoxychromone flavonoid — a capillarisin-type flavone that carries an oxygen-linked phenyl (“phenoxy”) group on the chromone core and, as its name says, lacks the 6-methoxy group of the parent capillarisin (a compound of Artemisia capillaris). On its own it is an obscure molecule; it earns a page for one reason: it is one of the two polyphenols that bioactivity-guided fractionation identified as the antidiabetic principles of Russian tarragon (Artemisia dracunculus), specifically the standardised ethanolic extract PMI-5011 ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}.

Its partner in that story is the dihydrochalcone DMC-2 (2’,4’-dihydroxy-4-methoxydihydrochalcone, also called 4-O-methyldavidigenin). Together the two were pulled out of tarragon extract by tracking the fractions that lowered a diabetic readout, and characterised as the compounds most responsible for the extract’s blood-glucose-lowering activity ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}.

Two honest caveats frame everything below. First, the isolated-compound evidence is entirely in-vitro — an H4IIE hepatoma PEPCK assay and cell-free/enzyme aldose-reductase screens ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}. Every in-vivo and human antidiabetic result is for the whole PMI-5011 extract, not the purified molecule ^{3Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →}. Second, the compound is not always present: a later phytochemical study of the extract using the DESIGNER fractionation approach reported no 6-demethoxycapillarisin in its material, with the dihydrochalcone DMC-2 carrying the activity — so its contribution varies by cultivar and preparation ^{4,5Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}.

The PMI-5011 Antidiabetic Story

To read this molecule correctly you have to read it as a fraction of an extract, not a drug. PMI-5011 is a standardised ethanolic extract of Russian tarragon developed as a botanical for type-2 diabetes / insulin resistance; in diabetic-animal and insulin-resistant-human-cell work the extract lowers blood glucose and improves insulin signalling ^{3Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →}. The compound-level program (Ribnicky, Logendra, Govorko, Poulev, Raskin, Cefalu and colleagues) then asked which molecules in the extract do that, and bioactivity-guided fractionation repeatedly returned 6-demethoxycapillarisin and DMC-2 as the polyphenolic hits ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}.

Where the isolate has documented activity, it is hepatic: in H4IIE hepatoma cells it suppresses expression of PEPCK — the rate-committing gluconeogenic enzyme — and thereby lowers glucose output, with a potency (IC₅₀ ≈ 43 µM for the PEPCK effect) reported by the Govorko study ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →}. The mechanism proposed is activation of the PI3K pathway, i.e. the compound mimics part of the insulin signal that normally shuts gluconeogenesis down ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →}. Separately, in the earlier aldose-reductase screen it was one of four fractions that inhibited aldose reductase (ALR2) — the polyol-pathway enzyme implicated in diabetic complications — the first report of the compound from A. dracunculus at all ^{2Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}.

The muscle / whole-body side of PMI-5011’s action — enhanced insulin-receptor and PI3K–Akt signalling in skeletal muscle, improved insulin sensitivity — is documented for the extract, and the mechanistic attribution to individual constituents is incomplete; the skeletal-muscle phospho-signalling work does not isolate 6-demethoxycapillarisin as the actor ^{3Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →}. So the fair summary is: hepatic PEPCK suppression is the compound’s own in-vitro signal; the muscle-insulin-sensitising effect is the extract’s.

What It's Used For

The compound-specific literature is small and preclinical — essentially the two bioactivity-guided isolation studies plus its appearance in the tarragon/PMI-5011 reviews. There is no pharmacology on the purified molecule beyond cell and enzyme assays.

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 in-vitro isolate work (cell or enzyme assays); the only in-vivo/human evidence is for the whole PMI-5011 extract, so isolate scores stay low by design.

01Hepatic Gluconeogenesis / PEPCKShaky34%One H4IIE hepatoma study; PEPCK ↓, IC₅₀ ≈ 43 µM, via PI3K ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →}

02Aldose-Reductase InhibitionShaky24%One bioassay-guided isolation; ALR2 inhibition at 3.75 µg/mL ^{2Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}

03Insulin Sensitisation (extract)Shaky20%Attributed to PMI-5011 extract, not the isolate ^{3Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →}

Mechanisms

The load-bearing, compound-specific thread is PEPCK suppression via PI3K activation in hepatoma cells — the one effect measured for the purified molecule ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →}. The aldose-reductase activity is fraction-level ^{2Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}, and the muscle insulin-sensitising action belongs to the whole tarragon extract, not the isolate ^{3,4Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →}.

Pharmacokinetics

There is no pharmacokinetic data on isolated 6-demethoxycapillarisin — no absorption, distribution, half-life or bioavailability figures for the pure compound in any species. What exists is at the extract level: PMI-5011 is an orally dosed standardised tarragon extract, and its constituents are assumed to undergo the usual phase-II conjugation (glucuronidation/sulfation) typical of dietary flavonoids, but this has not been characterised for this molecule specifically. The in-vitro potencies quoted above (µM in H4IIE cells, µg/mL in the ALR2 screen) are assay concentrations, not achievable plasma levels, and say nothing about what an oral dose would deliver. ADME work on the isolate is a clear, unfilled gap.

Clinical Trials

There are no clinical trials of isolated 6-demethoxycapillarisin. The compound has never been administered to humans as a purified substance. Human data exist only for the PMI-5011 tarragon extract in which it is one constituent — clinical work on the extract for insulin resistance / type-2 diabetes is tracked on the tarragon page, not here.

Last checked: July 2026.

Isolate vs. Plant Studies

The split here is unusually clean. The isolate’s entire evidence base is two in-vitro studies — the PEPCK/gluconeogenesis assay in H4IIE hepatoma cells ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →} and the aldose-reductase bioassay-guided isolation ^{2Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}. Both were designed to find which molecule in the extract acts, so they are mechanism-probing studies on fractions and purified compound, not efficacy studies. As an isolate mechanism base that is modest; as human evidence it is silent.

Everything with clinical or whole-organism weight is the plant/extract — PMI-5011, the standardised ethanolic tarragon extract, whose glucose-lowering and insulin-sensitising effects are shown in diabetic animals and insulin-resistant human muscle cells ^{3Reference 3Kheterpal I et al. · 2014Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cellsView study →}. And crucially, the extract’s activity cannot be pinned on 6-demethoxycapillarisin alone: it co-occurs with DMC-2 and other actives, its levels vary by cultivar, and a later fractionation of PMI-5011 found no 6-demethoxycapillarisin at all, with the dihydrochalcone doing the work ^{4,5Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. The correct framing: a plausible in-vitro contributor to a genuinely active extract — not a stand-alone antidiabetic, and not reliably present.

Its Role in Plants

In tarragon (Artemisia dracunculus), 6-demethoxycapillarisin is a minor polyphenol of the aerial parts, part of the broad flavonoid/phenolic pool that characterises the genus Artemisia ^{2,5Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. It belongs to the capillarisin family — 2-phenoxychromones best known from Artemisia capillaris (yin chen hao), where the parent capillarisin carries the 6-methoxy group this molecule lacks. These phenolics are the plant’s antioxidant/defence chemistry rather than signalling molecules; their concentration in tarragon is cultivar-dependent, with the Russian cytotype (the PMI-5011 source) differing markedly from French tarragon and some cytotypes lacking the compound entirely ^{4,5Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. This is plant biochemistry and should not be read as human pharmacology.

Prevalence in Nature

6-Demethoxycapillarisin is narrowly distributed and minor. Within the database its only source is Russian tarragon (Artemisia dracunculus), where it occurs in the aerial parts and is concentrated by ethanolic extraction into PMI-5011 ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}. Even there it is variable: reported in some cytotypes and preparations and undetectable in others ^{4,5Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. Structurally related 2-phenoxychromones (capillarisin itself) occur elsewhere in Artemisia, notably A. capillaris, but those are the methoxylated parent rather than this demethoxy compound. No quantified content figures for tarragon are established in the sources reviewed here.

Major Natural Sources

Source	Plant part	Reported content
Tarragon (Artemisia dracunculus, Russian)	aerial parts / ethanolic (PMI-5011) extract	minor polyphenol; variable, cytotype-dependent, sometimes absent — not individually quantified here 1,2,4,5Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →Reference 4Yu Y et al. · 2019The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistryView study →Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →

Only the tarragon occurrence is documented; the content is qualitative and cultivar-dependent, and the missing quantitation is tracked for a later pass.

Discovery & Synthesis

6-Demethoxycapillarisin entered this literature as a bioactivity-guided isolate, not a classical natural-product discovery. It was first reported from Artemisia dracunculus in 2006, when Logendra and colleagues ran a bioassay-guided fractionation of the antidiabetic tarragon extract for aldose-reductase inhibitors and identified it as one of four active compounds — the first report of the molecule from this plant and of its ALR2 activity ^{2Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}. The following year the Govorko study isolated it again by a different assay (PEPCK suppression) and characterised its antigluconeogenic effect ^{1Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →}. The compound as a class (a capillarisin-type 2-phenoxychromone) was known earlier from Artemisia capillaris work on capillarisin.

There is no commercial isolation or dedicated synthesis industry for the pure compound; it is obtained as a research isolate from tarragon fractionation, and reference material is available only in analytical quantities. Total-synthesis and manufacturing routes are not documented here.

Patents: not yet researched.

Toxicity & Safety

6-Demethoxycapillarisin carries a low flag, held with the caution that its safety is inferred, not tested. It is a minor dietary polyphenol of a culinary herb — tarragon is a common food flavouring — and it occurs in the PMI-5011 extract, which in reviews of Artemisia dracunculus has no acute toxicity or mutagenicity reported at doses relevant to human consumption ^{5Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. The compound itself appears in the literature as a protective (antidiabetic) agent, not a toxicant ^{1,2Reference 1Govorko D et al. · 2007In vitroPolyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitroView study →Reference 2Logendra S et al. · 2006In vitroBioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitroView study →}.

The honest limits are those of a preclinical-only isolate: there are no dedicated toxicity, genotoxicity or repeat-dose studies on the pure compound, and no human data of any kind on it in isolation — the safety read-across comes from the whole tarragon extract, not the molecule ^{5Reference 5Obolskiy D et al. · 2011ReviewArtemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — reviewView study →}. No drug-interaction studies exist for the isolate; any theoretical concern (e.g. additive glucose-lowering with antidiabetic drugs) applies to the extract in a medicinal context and is unquantified for this compound. At culinary tarragon exposure nothing suggests concern.

Safety at a Glance

✅ Low / no toxicity

• A minor polyphenol of an edible herb. Occurs in tarragon and its PMI-5011 extract, which shows no acute toxicity or mutagenicity at consumption-relevant doses.
• Appears as a protectant, not a toxicant. The isolate’s only studied effects are antidiabetic (PEPCK suppression, aldose-reductase inhibition) in vitro.
• Safety is inferred from the extract, not the isolate. No dedicated toxicity, genotoxicity or repeat-dose data on the pure compound, and no human data on it alone.
• Interactions untested. Any additive glucose-lowering concern belongs to medicinal tarragon-extract use, not culinary exposure, and is unquantified for this molecule.

Dosage

There is no established or recommended human dose for isolated 6-demethoxycapillarisin. It has never been given to a person, or an animal, as a purified compound. Its antidiabetic evidence is in-vitro assay concentrations, which are not convertible to human self-dosing:

Where a human-relevant dose exists it is for the PMI-5011 tarragon extract, not this constituent — refer to the tarragon monograph. The figures above are research concentrations, not a personal recommendation.

References

1. Govorko D, Logendra S, Wang Y, et al. (2007). Polyphenolic compounds from Artemisia dracunculus L. inhibit PEPCK gene expression and gluconeogenesis in an H4IIE hepatoma cell line — in vitro. American Journal of Physiology - Endocrinology and Metabolism. https://pubmed.ncbi.nlm.nih.gov/17848630/
2. Logendra S, Ribnicky DM, Yang H, et al. (2006). Bioassay-guided isolation of aldose reductase inhibitors from Artemisia dracunculus — in vitro. Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/16806328/
3. Kheterpal I, Scherp P, Kelley L, et al. (2014). Bioactives from Artemisia dracunculus L. enhance insulin sensitivity via modulation of skeletal muscle protein phosphorylation — extract, human muscle cells. Nutrition. https://pubmed.ncbi.nlm.nih.gov/24985106/
4. Yu Y, Simmler C, Kuhn P, et al. (2019). The DESIGNER approach helps decipher the hypoglycemic bioactive principles of Artemisia dracunculus L. (Russian tarragon) — phytochemistry. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/31815461/
5. Obolskiy D, Pischel I, Feistel B, et al. (2011). Artemisia dracunculus L. (tarragon): a critical review of its traditional use, chemical composition, pharmacology, and safety — review. Journal of Agricultural and Food Chemistry. https://pubmed.ncbi.nlm.nih.gov/21942448/