Compound Monograph
6′-O-Galloylpaeoniflorin
6′-O-galloylpaeoniflorin (GPF) is a galloylated monoterpene glycoside of peony root (Paeonia lactiflora) — paeoniflorin carrying a gallic-acid ester — studied in cell and animal models as an Nrf2-activating antioxidant and a weak natural anti-androgen. There are no human data.
Sources · 3
Where Does It Come From?
6′-O-Galloylpaeoniflorin is a naturally occurring galloylated monoterpene glycoside (paeoniflorin galloyl ester), found in White peony root and 2 other sources. It is well tolerated orally (low toxicity).
Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
6′-O-Galloylpaeoniflorin at a Glance
6′-O-galloylpaeoniflorin, usually abbreviated GPF, is a galloylated monoterpene glycoside from the root of peony (Paeonia lactiflora). Structurally it is paeoniflorin — peony’s principal glycoside — carrying an extra galloyl (gallic-acid) ester on the glucose 6′-position. That single addition is the whole story of the molecule: paeoniflorin itself is a weak antioxidant and shows no androgen-receptor activity, whereas the galloyl group turns GPF into a radical scavenger and a weak androgen-receptor antagonist 1,
Interest in GPF runs along two lines. The larger body of work treats it as an Nrf2-activating antioxidant and cytoprotectant, tested in cell and rodent models of cerebral ischaemia, osteoporosis, Helicobacter pylori gastritis, lung-cancer growth and UV-stressed skin 2,
The honest headline is that all of this is preclinical. Every result below comes from the isolated compound in cell culture or animals; there are no human trials, and no human pharmacokinetic data, for GPF. It should be read as a mechanistically interesting minor peony constituent, not as a demonstrated therapeutic.
Galloyl Ester of Paeoniflorin → Androgen Modulation & Antioxidant Activity
The defining fact about GPF is that its activity is conferred by the galloyl moiety, not by the paeoniflorin scaffold.
When Washida and colleagues fractionated Nara-grown peony root looking for androgen modulators, they isolated a family of galloyl/benzoyl monoterpene glycosides — 3′-O-galloylpaeoniflorin, 6′-O-galloylalbiflorin, pentagalloylglucose, 6′-O-benzoylpaeoniflorin and 6′-O-galloylpaeoniflorin — and tested them against the androgen receptor (AR). GPF showed only weak AR binding (roughly 12% inhibition at 120 µg/mL), far below the strong binders in the set (6′-O-galloylalbiflorin, IC₅₀ ≈ 33.7 µg/mL; pentagalloylglucose, IC₅₀ ≈ 4.1 µg/mL). Decisively, the parent paeoniflorin — and albiflorin — showed no AR activity at all, so the galloyl ester is what creates the receptor interaction. GPF (with the other four glycosides) also inhibited growth of androgen-dependent LNCaP-FGC prostate-cancer cells and behaved as an AR antagonist 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →.
The same galloyl group underlies GPF’s antioxidant behaviour. The gallic-acid ester carries the phenolic hydroxyls that let GPF scavenge free radicals directly and drive the Nrf2-based cytoprotection seen across the cell and animal studies below 2,
What It's Used For
The evidence base is a cluster of single-group, isolated-compound studies, unusually consistent in mechanism (radical scavenging + Nrf2/antioxidant-enzyme induction) but spread thinly across many disease models and entirely preclinical.
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here rests on isolated-compound cell and rodent work only, so the scores are modest by design and none should be read as clinical support.
The best-supported and most unifying activity — all isolate, in cell and rodent models. GPF directly scavenges the DPPH radical, superoxide, hydroxyl radical and hydrogen-peroxide-generated intracellular ROS, and it induces the PI3K/Akt → Nrf2 antioxidant-response programme, raising antioxidant-enzyme output and reducing oxidative damage to DNA, lipids and proteins 7Reference 7Yao CW, et al. (2013). 6′-O-galloylpaeoniflorin protects human keratinocytes against oxidative stress-induced cell damage. Biomolecules & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/24244822/View study →.
This same mechanism recurs across its neuroprotection 6Reference 6Wen Z, et al. (2018). 6′-O-Galloylpaeoniflorin attenuates cerebral ischemia reperfusion-induced neuroinflammation and oxidative stress via PI3K/Akt/Nrf2 activation. Oxidative Medicine and Cellular Longevity. https://pubmed.ncbi.nlm.nih.gov/29765506/View study →, anti-osteoclast 5Reference 5Liu W, et al. (2021). 6′-O-Galloylpaeoniflorin attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting reactive oxygen species and MAPKs/c-Fos/NFATc1 signaling pathway. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33897430/View study → and anti-gastritis 2Reference 2Zhang Y, et al. (2022). 6′-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/35964411/View study → studies, where Nrf2 activation is the shared node.
Gap: these are in-vitro and animal antioxidant readouts of the pure compound; no human antioxidant outcome rests on GPF, and because it is a low-abundance root constituent, whole-peony antioxidant capacity cannot be credited to it 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →.
Isolate, in vitro and in vivo. In PC12 cells subjected to oxygen–glucose deprivation, GPF reduced oxidative stress, inflammation, injury and apoptosis; in rats with cerebral ischaemia-reperfusion injury it reduced infarct volume and improved neurological deficits. Both effects tracked increased phospho-Akt and Nrf2 and were abolished by the PI3K inhibitor Ly294002 or Nrf2 knockdown, tying the protection to PI3K/Akt/Nrf2 activation 6Reference 6Wen Z, et al. (2018). 6′-O-Galloylpaeoniflorin attenuates cerebral ischemia reperfusion-induced neuroinflammation and oxidative stress via PI3K/Akt/Nrf2 activation. Oxidative Medicine and Cellular Longevity. https://pubmed.ncbi.nlm.nih.gov/29765506/View study →.
Gap: a single rodent ischaemia model from one group, with no dosing/pharmacokinetic bridge to humans and no clinical follow-up.
Isolate, in vitro and in vivo. In RANKL-stimulated mouse bone-marrow macrophage cultures, GPF suppressed osteoclast differentiation by lowering reactive oxygen species and dampening MAPKs/c-Fos/NFATc1 signalling; in ovariectomised mice it relieved oestrogen-deficiency bone loss 5Reference 5Liu W, et al. (2021). 6′-O-Galloylpaeoniflorin attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting reactive oxygen species and MAPKs/c-Fos/NFATc1 signaling pathway. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33897430/View study →.
Gap: preclinical only; the anti-resorptive effect is inferred from an antioxidant/RANKL mechanism in mice, with no human bone-density evidence.
Isolate, in vitro and in vivo. In non-small-cell lung-cancer lines (A549, H1299), GPF at 50–100 µM was cytotoxic and inhibited clonogenicity, invasion and migration; it also slowed A549 xenograft growth in mice. The proposed mechanism is an AMPK → miR-299-5p → ATF2 axis, with GPF raising AMPK activity and miR-299-5p to suppress the pro-tumour transcription factor ATF2 4Reference 4Gao J, et al. (2020). 6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis. Respiratory Research. https://pubmed.ncbi.nlm.nih.gov/32014006/View study →.
Gap: one cell/xenograft study; the concentrations are high, and there is no selectivity, pharmacokinetic or human data.
Isolate, in vitro. GPF was isolated from peony root as one of several androgen modulators and showed weak androgen-receptor binding (~12% at 120 µg/mL) plus AR antagonism, inhibiting androgen-dependent LNCaP-FGC prostate-cancer cell growth. The parent paeoniflorin was inactive, so the effect belongs to the galloyl ester — but among peony’s galloyl glycosides GPF is the weak one, well behind 6′-O-galloylalbiflorin and pentagalloylglucose 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →.
Gap: a single receptor-binding/cell study; no functional anti-androgen data in animals or humans, and the popular androgenetic-alopecia framing is an extrapolation the data do not yet support.
Isolate, in vitro. In HaCaT human keratinocytes, GPF protected against hydrogen-peroxide- and UVB-induced oxidative damage and apoptosis, reducing DNA strand breaks, lipid peroxidation and protein carbonylation 7,
Gap: keratinocyte-culture and enzyme-assay data only; no clinical cosmetic or photoprotection outcome, and the tyrosinase effect was minor relative to pentagalloylglucose and gallic acid in the same screen 9Reference 9A novel high-resolution monophenolase/diphenolase/radical scavenging profiling for the rapid screening of natural whitening candidates from Paeonia lactiflora root and their mechanism study with molecular dockingView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| Reactive oxygen species (DPPH, O₂·⁻, ·OH, H₂O₂) | direct radical scavenging; lowers intracellular ROS | antioxidant / cytoprotection; skin |
| PI3K/Akt → Nrf2/ARE | promotes Nrf2 nuclear translocation, induces antioxidant enzymes | antioxidant; neuroprotection |
| RANKL → MAPKs / c-Fos / NFATc1 | suppresses osteoclast differentiation (ROS-dependent) | anti-osteoporotic |
| AMPK → miR-299-5p → ATF2 | raises AMPK/miR-299-5p, lowers ATF2 → ↓ proliferation & invasion | anticancer (NSCLC) |
| Androgen receptor | weak binding + antagonism → ↓ androgen-dependent LNCaP-FGC growth | androgen modulation |
| Tyrosinase (monophenolase) | selective monophenolase inhibition | skin whitening |
| NF-κB / inflammatory cytokines | dampened inflammatory response, downstream of ROS/Nrf2 | anti-inflammatory (gastritis) |
The load-bearing point is that one mechanism — radical scavenging plus PI3K/Akt/Nrf2 antioxidant induction — accounts for most of the organ-protective claims; the AR antagonism is a separate, weaker activity of the same galloyl group.
Pharmacokinetics
There is essentially no pharmacokinetic characterisation of GPF. As a large, polar galloylated glycoside, it would be expected to have low oral bioavailability — glycosides are typically cleaved by gut microbiota and galloyl esters by esterases before absorption — but this has not been measured for GPF, and no absorption, distribution, metabolism, half-life or active-metabolite data exist. This matters: the antioxidant and anticancer effects were produced by direct application to cells (50–100 µM) or by injection/gavage in rodents, so they cannot be assumed to translate to oral human exposure at achievable plasma levels. Bioavailability is the central unknown that undercuts every downstream claim.
Clinical Trials
There are no clinical trials of 6′-O-galloylpaeoniflorin. All human-relevant evidence is preclinical (isolated-compound cell and rodent studies); any peony human data belong to standardised total glucosides of peony or the whole root, not to this minor constituent.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| — | — | — | Antioxidant/Nrf2, neuroprotection, anti-osteoclast, anticancer, AR-antagonist, keratinocyte |
Last checked: July 2026.
Isolate vs. Plant Studies
Unusually for this database, the GPF literature is almost entirely isolate-based — which is a double-edged fact. On one hand it means the effects are attributed to the defined molecule, not an extract 4,
Prevalence in Nature
6′-O-galloylpaeoniflorin is a minor galloyl ester of paeoniflorin occurring in the roots of peony (Paeonia lactiflora) — the same Paeoniae Radix material that yields paeoniflorin, albiflorin and the other galloyl/benzoyl glycosides 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →. It is consistently described as a low-content root constituent, well below the pharmacopoeial marker paeoniflorin 1,
Discovery & Synthesis
GPF entered the literature as one of peony root’s galloylated monoterpene glycosides, catalogued during the phytochemical mapping of Paeonia glycosides in the later twentieth century. Its pharmacological profile was sharpened in 2009, when Washida, Itoh, Iwashita and Nomoto isolated it (as a known compound, compound 5) alongside the newly described 3′-O-galloylpaeoniflorin while screening Nara-grown peony root for androgen modulators, and reported its weak AR binding and AR-antagonist activity 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →. There is no documented total synthesis of GPF; it is obtained by isolation from peony root (chromatographic fractionation of the galloyl-glycoside fraction), and the “galloyl ester of paeoniflorin” relationship means it is most naturally viewed as a biosynthetic galloylation of the parent glycoside rather than a synthetic target. No commercial-scale production route is established beyond research-quantity extraction.
Patents: not yet researched.
Toxicity & Safety
GPF carries a low flag. It is a naturally occurring, low-abundance constituent of a widely used food-adjacent medicinal root, and the isolated-compound studies to date report protective (antioxidant, cytoprotective) rather than toxic effects across brain, bone, gastric-mucosa and skin models 2,
- No toxicity signal in preclinical work. The isolated compound behaved as an antioxidant/cytoprotectant, not a toxin, in the cell and rodent models tested.
- Low, food-adjacent natural exposure. GPF is a minor constituent of peony root, an established traditional medicine; dietary/herbal exposure is small.
- Weak anti-androgen activity. GPF antagonises the androgen receptor in vitro; a hormone-modulating molecule warrants caution in androgen-sensitive contexts, even though functional or human data are absent 1Reference 1Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, JapanView study →.
- No human safety, interaction or pregnancy data. Safety rests on the absence of preclinical harm signals, not on positive testing; do not read the low badge as an all-clear.
Dosage
No human dose is established for 6′-O-galloylpaeoniflorin, and none should be inferred. The figures in the literature are experimental exposures, not recommendations:
| Setting | Typical exposure |
|---|---|
| Cell studies (antioxidant, anticancer) | ~50–100 µM applied directly to cells |
| Rodent models (ischaemia, osteoporosis, xenograft) | injected/gavaged doses in mice and rats |
| Human oral dosing | not established — no pharmacokinetic bridge |
Herbal exposure is indirect and minor: GPF is a low-content peony-root constituent, and peony’s human evidence is for standardised whole-root preparations (total glucosides of peony), not this molecule. These are doses used in research and are not a personal recommendation.
References
- Washida K, Itoh Y, Iwashita T, Nomoto K (2009). Androgen modulators from the roots of Paeonia lactiflora (paeoniae radix) grown and processed in Nara prefecture, Japan. Chemical & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/19721258/
- Zhang Y, et al. (2022). 6′-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/35964411/
- Xu SY, et al. (2024). Genus Paeonia monoterpene glycosides: a systematic review on their pharmacological activities and molecular mechanisms. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/38432036/
- Gao J, et al. (2020). 6′-O-galloylpaeoniflorin regulates proliferation and metastasis of non-small cell lung cancer through AMPK/miR-299-5p/ATF2 axis. Respiratory Research. https://pubmed.ncbi.nlm.nih.gov/32014006/
- Liu W, et al. (2021). 6′-O-Galloylpaeoniflorin attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting reactive oxygen species and MAPKs/c-Fos/NFATc1 signaling pathway. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/33897430/
- Wen Z, et al. (2018). 6′-O-Galloylpaeoniflorin attenuates cerebral ischemia reperfusion-induced neuroinflammation and oxidative stress via PI3K/Akt/Nrf2 activation. Oxidative Medicine and Cellular Longevity. https://pubmed.ncbi.nlm.nih.gov/29765506/
- Yao CW, et al. (2013). 6′-O-galloylpaeoniflorin protects human keratinocytes against oxidative stress-induced cell damage. Biomolecules & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/24244822/
- Yao CW, et al. (2014). Cytoprotective effects of 6′-O-galloylpaeoniflorin against ultraviolet B radiation-induced cell damage in human keratinocytes. In Vitro Cellular & Developmental Biology - Animal. https://pubmed.ncbi.nlm.nih.gov/24687317/
- Chu C, et al. (2022). A novel high-resolution monophenolase/diphenolase/radical scavenging profiling for the rapid screening of natural whitening candidates from Paeonia lactiflora root and their mechanism study with molecular docking. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/34506940/
