Herbacetin inhibits ornithine decarboxylase (ODC) (IC₅₀ = 3.2 μM). [2]
Herbacetin broadly inhibits CYP450 enzymes: CYP1A2 (IC₅₀ = 0.86 μM), CYP2C9 (IC₅₀ = 0.65 μM), CYP2C19 (IC₅₀ = 0.92 μM), CYP2D6 (IC₅₀ = 0.94 μM), CYP3A4 (IC₅₀ = 1.26 μM). [3]

Herbacetin (5–20 μM) reduced lipid accumulation in HepG2 cells by upregulating AMPK phosphorylation and downregulating SREBP-1c, FAS, ACC, and HMGCR expression. [1]
Herbacetin inhibited breast cancer cell proliferation (MDA-MB-231: IC₅₀ = 15.3 μM; BT-549: IC₅₀ = 16.7 μM) by inducing G1 cell cycle arrest and apoptosis. [2]
Herbacetin (10–40 μM) suppressed melanoma cell (A375/B16F10) migration/invasion and HUVEC tube formation by inhibiting EGFR-ERK/AKT signaling and MMP9 expression/activity. [4]

Oral herbacetin (10 mg/kg/day × 30 days) ameliorated insulin resistance and reduced hepatic lipid accumulation in high-fat diet-fed mice. [1]
Herbacetin (20 mg/kg, i.p., q3d × 6 weeks) suppressed intestinal polyp formation by 65% in APC^Min/+ mice and inhibited HCT116 xenograft tumor growth by 58% in nude mice. [2]
Herbacetin (oral; 20 mg/kg) in mice with obesity-associated insulin resistance (OIR) dramatically lowers body weight, blood glucose, plasma insulin, and HOMA-IR activity. In 0.5% DMSO, the herbacetin is dissolved [1]. Without appearing to be harmful, herbacetin (intraperitoneal injection; 0.4, 2, 10, or 20 mg/kg; BW) decreases the quantity and size of polyps in APCMin+ mice [2].

ODC inhibition assay: Recombinant human ODC incubated with [1-¹⁴C]ornithine and herbacetin (0–20 μM). Released ¹⁴CO₂ quantified via scintillation counting. [2]
CYP450 inhibition assay: Human liver microsomes incubated with NADPH, probe substrates, and herbacetin (0–10 μM). Metabolite formation measured by LC-MS/MS. [3]

ipid accumulation: HepG2 cells treated with herbacetin (5–20 μM) for 24 h, stained with Oil Red O, and quantified spectrophotometrically.
Western blot: AMPK/SREBP-1c pathway proteins analyzed in HepG2 cells after 24 h treatment. [1]
MTT assay: Breast cancer cells treated with herbacetin (0–50 μM) for 48 h; viability measured via formazan formation.
Flow cytometry: Annexin V/PI staining for apoptosis and propidium iodide for cell cycle analysis. [2]
Transwell invasion: Melanoma cells seeded in Matrigel-coated chambers with herbacetin (10–40 μM); invaded cells counted after 24 h.
Gelatin zymography: MMP9 activity in cell supernatants measured after 48 h treatment. [4]

Obesity associated insulin resistance induction (OIR)[1]
Obesity associated insulin resistance was induced in male C57BL/6 J mice by the administration of high percent beef tallow-containing fat diet for 10 weeks. The diet compositions of high and normal fat are given in Table 1. After 10 weeks of high or normal fat administration, all animals were used for further experiments to check the effectiveness of herbacetin. Especially, we selected a blood glucose range of more than 180 mg/dl to be considered as diabetic after 10 weeks high fat administrations. Afterwards, herbacetin (dissolved in 0.5% dimethyl sulfoxide (DMSO)) was given daily along with a high fat diet for the next 5 weeks. The detailed experimental design is shown in Fig. 2.

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In vivo studies using the APCMin+ mouse model[2]
Male C57BL/6J(Min/+) mice were maintained under “specific pathogen-free” conditions. APCMin+ male mice were bred with C57BL/6J APC wildtype female mice. The progeny were genotyped by PCR assay to determine whether they were heterozygous for the min allele or were homozygous wildtype. APCMin+ male or female progeny were randomly assigned to groups after weaning at 3 weeks. Mice (5~6 weeks old) were divided into 3 groups: 1) untreated vehicle group (n = 8); 2) mice treated with 0.4 mg herbacetin/kg of body weight (n = 8); and 3) mice treated with 2 mg herbacetin/kg of body weight (n = 8). herbacetin or vehicle was injected i.p. 3 times a week for 8 weeks.

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In vivo studies using the xenograft mouse model[2]
Athymic nude mice (6 week old nu/nu female mice) were inoculated in the right flank with HCT116 cells (2×106 cells/mouse). Mice were maintained under “specific pathogen-free” conditions based on the guidelines established by the University of Minnesota Institutional Animal Care and Use Committee. For treatment by I.P injection, tumors were allowed to grow to an average of ~74.1 ± 56 mm3 and then, based on tumor volume, mice were divided into groups to obtain a similar average tumor volume. Mice were divided into four groups as follows: 1) untreated vehicle group (n = 10); 2) 0.4 mg herbacetin/kg of body weight (n = 10); 3) 2 mg herbacetin/kg of body weight (n = 10); and 4) 200 mg DFMO/kg of body weight (n = 10). herbacetin, DFMO or vehicle (5% DMSO in 10% tween 20) was injected 3 times per week for 14 days. For treatment by oral administration, tumors were allowed to grow to an average of ~51.3 ± 51.6 mm3 and then mice were divided into 2 groups with a similar average tumor volume as follows: 1) untreated vehicle group (n = 15) and 2) herbacetin at 100 mg/kg (n = 19). Treatment with herbacetin was initiated on Day 17 after inoculation of cells and continued to Day 35 (~3wks) and was administered by oral gavage 5 times a week. Tumor volume was measured 2 times a week and body weight was measured once a week. Herbacetin was prepared in 2.5% DMSO/5% PEG 400/5% Tween-80 in 1× PBS and sonicated for 20 min. Tumor volume was calculated from measurements of 2 diameters of the individual tumor base using the following formula: tumor volume (mm3) = (length × width × height × 0.52). Mice were monitored until tumors reached 1 cm3 total volume, at which time mice were euthanized and tumors extracted.

Herbacetin potently inhibits multiple CYP450 isoforms, indicating high risk for drug-drug interactions. [3]

[1]. Herbacetin, a flaxseed flavonoid, ameliorates high percent dietary fat induced insulin resistance and lipid accumulation through the regulation of hepatic lipid metabolizing and lipid-regulating enzymes. Chem Biol Interact. 2018 May 25;288:49-56.

[2]. Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity. Cancer Res. 2016 Mar 1;76(5):1146-1157.

[3]. Herbacetin Broadly Blocks the Activities of CYP450s by Different Inhibitory Mechanisms [published online ahead of print, 2021 Jun 11]. Planta Med. 2021;10.1055/a-1502-7131.

[4] Herbacetin suppressed MMP9 mediated angiogenesis of malignant melanoma through blocking EGFR-ERK/AKT signaling pathway. Biochimie. 2019;162:198-207.

Herbacetin is a pentahydroxyflavone that is kaempferol substituted by a hydroxy group at position 8. It is a natural flavonoid from flaxseed which exerts antioxidant, anti-inflammatory and anticancer activities. It has a role as an EC 4.1.1.17 (ornithine decarboxylase) inhibitor, an antineoplastic agent, an apoptosis inducer, an angiogenesis inhibitor, a plant metabolite, an antilipemic drug, an anti-inflammatory agent and an EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor. It is a pentahydroxyflavone and a 7-hydroxyflavonol. It is functionally related to a kaempferol.
Herbacetin has been reported in Sinocrassula indica, Rhodiola crenulata, and other organisms with data available.
See also: Larrea tridentata whole (part of).

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Herbacetin is a flaxseed-derived flavonoid with antidiabetic and antitumor activities. [1]
Mechanism: Allosterically inhibits ODC by binding outside its active site, depleting polyamines. [2]
Herbacetin blocks melanoma angiogenesis via EGFR-ERK/AKT-MMP9 axis suppression. [4]

C15H10O7

302.2357

302.042

C, 59.61; H, 3.34; O, 37.05

527-95-7

5280544

Light yellow to yellow solid powder

1.799

618.7±55.0 °C at 760 mmHg

284ºC

239.0±25.0 °C

0.0±1.9 mmHg at 25°C

1.823

1.14

5

7

1

22

480

0

O1C(C2C([H])=C([H])C(=C([H])C=2[H])O[H])=C(C(C2C(=C([H])C(=C(C1=2)O[H])O[H])O[H])=O)O[H]

ZDOTZEDNGNPOEW-UHFFFAOYSA-N

InChI=1S/C15H10O7/c16-7-3-1-6(2-4-7)14-13(21)12(20)10-8(17)5-9(18)11(19)15(10)22-14/h1-5,16-19,21H

3,5,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one

Herbacetin; 8-hydroxy Kaempferol; 527-95-7; 8-Hydroxykaempferol; 3,5,7,8-tetrahydroxy-2-(4-hydroxyphenyl)chromen-4-one; 736854V2KE; CHEBI:27673; DTXSID70415061; DTXCID30365912; Isoarticulatidin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~330.86 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (8.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)