NF-κB (nuclear factor kappa B) - zingerone suppresses NF-κB activation. [2]
Cyclin D1 - zingerone reduces cyclin D1 expression. [3]
Various pro-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α) - zingerone downregulates these cytokines. [2]
Antioxidant enzymes (SOD, CAT, GPx, GSH) - zingerone increases their activity. [1][2]

- Zingerone protects in vitro DNA against stannous chloride-induced and hydrogen peroxide-induced oxidative DNA damage. [1]
- Zingerone suppresses ferric ascorbate-induced lipid peroxidation in rat brain. [1]
- Zingerone has scavenging effect against peroxynitrite formed from the reaction of superoxide and nitric oxide. [1]
- In human neuroblastoma cells (SH-SY5Y, BE(2)C, BE(2)-M17), zingerone (0.25-2 mM for 24-48 h) significantly suppressed cell viability in a dose- and time-dependent manner as measured by MTT assay. In BE(2)-M17 cells, zingerone (1-2 mM for 24 h) induced mitotic arrest, particularly at prometaphase, increased the number of pH3-positive cells, and reduced colony-forming activity (0.5-2 mM for 2 weeks). [3]
- In BE(2)-M17 cells, zingerone (1-2 mM for 24 h) reduced cyclin D1 expression, but did not affect cyclin B1, Aurora B, PLK-1, or p53 expression. Zingerone (1-2 mM for 72-96 h) increased cleavage of caspase-3 and PARP-1, indicating induction of apoptosis. [3]
- In BE(2)-M17 cells, zingerone (2 mM for 24 h) increased the number of cells with condensed chromosomes and pH3-positive cells, as shown by immunofluorescence and flow cytometry. [3]
- In a clonogenic assay, zingerone (0.5, 1, 2 mM) treatment of BE(2)-M17 cells for two weeks significantly reduced colony area in a dose-dependent manner (PANOVA < 0.001). [3]

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Zingerone is a non-toxic methoxyphenol that has powerful anti-inflammatory, anti-diabetic, anti-lipolytic, anti-diarrheic, and antispasmodic properties[1].
Zingerone (0–2 mM) reduces neoblastoma cell survival[3].
Zingerone (0–2 mM) decreases cyclin D1 expression and increases caspase-3 and PARP-1 cleavage in BE(2)-M17 cells[3].

- Alloxan-induced diabetes model (rat): In male Wistar rats, alloxan (100 mg/kg, i.p., once) induced diabetes. Oral administration of zingerone (50 or 100 mg/kg b.wt./day for 21 days) significantly reduced blood glucose levels (e.g., day 21: 144.7 ± 4.26 mg/dL for 50 mg/kg, 122.6 ± 1.80 mg/dL for 100 mg/kg vs. 245.00 ± 11.12 mg/dL in diabetic control), increased serum insulin levels, increased serum amylase, improved lipid profile (decreased TC, TG, LDL-C; increased HDL-C), decreased liver enzymes (ALT, AST, ALP), decreased lipid peroxidation (MDA), and increased antioxidant enzyme activities (SOD, CAT, GPx, GSH). Zingerone also decreased NF-κB-p65 levels and reduced pro-inflammatory cytokines (IL-1β, IL-2, IL-6, TNF-α). [2]
- Neuroblastoma xenograft model (mouse): In BALB/c mice injected subcutaneously with Renca cells (5 × 10⁶), intraperitoneal administration of zingerone (10 mg/kg in saline, daily for 7 days) significantly reduced tumor size compared to saline control. Immunohistochemistry of tumor tissues showed reduced cyclin D1 expression, increased pH3-positive cells, and increased TUNEL-positive apoptotic cells in zingerone-treated mice. [3]

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Zingerone (50, 100 mg/kg, p.o. daily for 21 days) protects against alloxan-induced diabetes in rats by reducing oxidative stress and inflammation[2].
Zingerone (10 mg/kg, i.p.) slows the growth of tumors by stopping the mitotic cycle, preventing cell division, and inducing apoptosis[3].

- Lipid peroxidation assay: Lipid peroxidation was estimated in post-mitochondrial supernatant by measuring malondialdehyde (MDA) formation. Results were expressed as nmol MDA formed/g tissue using a molar extinction coefficient of 1.56 × 10⁵/M per cm. [2]
- Superoxide dismutase (SOD) assay: SOD activity in post-mitochondrial supernatant was analyzed using the method of Marklund and Marklund (1974). Units of SOD activity were expressed as IU/L. [2]
- Catalase (CAT) assay: Catalase activity in post-mitochondrial supernatant was assessed by the method of Claiborne (1985). CAT activity was calculated as nmol H₂O₂ consumed/min per mg protein. [2]
- Reduced glutathione (GSH) assay: GSH activity was assessed in post-mitochondrial supernatant by the method of Carlberg and Mannervik (1975). GSH content was calculated as mmol 5,5′-dithio-bis-(2-nitrobenzoic acid) conjugate formed/g tissue using a molar extinction coefficient of 13.6 × 10³/M per cm. [2]
- Glutathione peroxidase (GPx) assay: GPx activity was assessed by the method of Mohandas et al. (1984). Levels were calculated as nmol NADPH oxidized/min per mg protein with a molar extinction coefficient of 6.22 × 10³/M per cm. [2]

- Cell viability assay (MTT): Cells (BE(2)-M17: 6 × 10⁴, BE(2)C: 6 × 10⁴, SH-SY5Y: 3 × 10⁴ per well in 24-well plates) were treated with zingerone (0.25-2 mM) for 24 or 48 h. MTT was added and incubated for 2 h at 37°C. Formazan crystals were dissolved in DMSO, and absorbance was measured at 590 nm. [3]
- Colony formation assay: 500 BE(2)-M17 cells were plated in 60-mm dishes and incubated with zingerone (0.5, 1, 2 mM) for two weeks. Cells were fixed with methanol and stained with crystal violet. Colony area was measured using ImageJ software. [3]
- Immunofluorescence cytochemistry: BE(2)-M17 cells treated with zingerone (2 mM for 24 h) were fixed with ice-cold 100% methanol, blocked with 5% BSA/0.3% Tween-20 in PBS, and incubated with primary antibodies (anti-pH3, anti-β-tubulin, anti-γ-tubulin) overnight at 4°C, followed by secondary antibodies (Alexa-488 or Alexa-594) and Hoechst33342. Images were captured using a fluorescence microscope. [3]
- Cell cycle analysis (flow cytometry): Cells were fixed with 70% ethanol, permeabilized with 0.25% Triton X-100, incubated with anti-pH3 antibody for 2 h, then with secondary antibody. Cells were treated with RNase A and propidium iodide (PI), and analyzed by flow cytometry for pH3-positive cells. [3]
- Western blot analysis: BE(2)-M17 cells were treated with zingerone (1-2 mM for 24-96 h), harvested in NP-40 lysis buffer, and centrifuged. Protein lysates were resolved on SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against cyclin D1, cyclin B1, PLK1, Aurora B, PARP-1, caspase-3, p53, and α-tubulin. Bands were visualized with chemiluminescent substrate. [3]
- Apoptosis detection (TUNEL assay): Paraffin-embedded tumor sections were deparaffinized, rehydrated, and subjected to TUNEL assay using a commercial kit according to the manufacturer's protocol. Nuclei were counterstained with hematoxylin. TUNEL-positive cells were counted under a light microscope. [3]
- Immunohistochemistry: Frozen tumor sections (30 μm) were cut using a freezing microtome, placed on gelatin-coated slides, and incubated with anti-cyclin D1 or anti-pH3 antibodies at 4°C overnight. Antigen sites were visualized using the ABC kit and DAB. Staining intensity was measured using ImageJ software. [3]
- Immunoassay for NF-κB and cytokines (ELISA): Serum levels of NF-κB-p65, IL-1β, IL-2, IL-6, and TNF-α were estimated using commercial ELISA kits according to the manufacturer's protocols. Plates were read at 450 nm. [2]

- Alloxan-induced diabetes model in rats: Male Wistar rats (160-200 g) were divided into 5 groups (n=10/group). Diabetes was induced by intraperitoneal injection of alloxan (100 mg/kg b.wt. dissolved in 0.9% NaCl). After 7 days (when blood glucose >250 mg/dL), zingerone was administered orally (50 or 100 mg/kg b.wt./day) for 21 days. Glibenclamide (4.5 mg/kg b.wt./day) was used as standard control. At the end of the study, animals were sacrificed, and blood and liver tissues were collected for analysis. [2]
- Neuroblastoma xenograft model in mice: Male BALB/c mice (6 weeks old) were injected subcutaneously with Renca cells (5 × 10⁶ cells mixed 1:1 with Matrigel). After 7 days, mice were injected intraperitoneally daily with zingerone (10 mg/kg in saline) or saline alone for one week (n=4 mice/group). At 14 days after cell injection, mice were sacrificed, and tumors were extracted. Tumor volume was calculated as 0.5 × (width × length × height). [3]

Metabolism / Metabolites
Following oral or intraperitoneal injection of 100 mg/kg Zingerone in rats, it is primarily excreted in the urine as glucuronide and/or sulfate conjugates. Unmetabolized Zingerone accounts for 50-55% of the dose, while reduction to methanol also occurs (11-13%). Side-chain oxidation following oral or intraperitoneal injection of 100 mg/kg Zingerone in rats occurs at three possible sites, with oxidation at position 3 being dominant, generating C-6 to C-2 metabolites. Identified metabolites account for 95-97% of the dose. Bile studies and in vitro (rat) studies on cecal microbiota indicate that several urinary O-demethylated metabolites (Zingerone) originate from bacteria.

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- Pharmacokinetics of zingerone revealed that administration either orally or intraperitoneally results in oxidation of the side chain at all available sites. During catabolism of zingerone, glucuronidation and sulfation occur, leading to excretion of glucuronide compounds and sulfate conjugates in urine within 24 hours of consumption. [1]

- Zingerone is described as a nontoxic compound. [1]
- In the alloxan-induced diabetes rat model, zingerone at doses of 50 and 100 mg/kg b.wt. for 21 days was well tolerated with no reported mortality. [2]
- In the mouse neuroblastoma xenograft model, zingerone at 10 mg/kg (i.p., daily for 7 days) was well tolerated. [3]
- Zingerone is not cytotoxic to normal cells (as indicated in supplementary materials of [3]).

[1]. A Review on Pharmacological Properties of Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone). ScientificWorldJournal. 2015;2015:816364.

[2]. Zingerone (4-(4-hydroxy-3-methylphenyl) butan-2-one) protects against alloxan-induced diabetes via alleviation of oxidative stress and inflammation: Probable role of NF-kB activation. Saudi Pharm J. 2018 Dec;26(8):1137-1145.

[3]. Zingerone Suppresses Tumor Development through Decreasing Cyclin D1 Expression and Inducing Mitotic Arrest. Int J Mol Sci. 2018 Sep 19;19(9):2832.

Zingerone is a methyl ketone with the structure 4-phenylbut-2-one, in which the 3- and 4-positions of the benzene ring are replaced by methoxy and hydroxyl groups, respectively. It is the main pungent component of ginger. Zingerone has various effects, including antioxidant, anti-inflammatory, radiation protection, antiemetic, flavoring, spice, and plant metabolism. It belongs to the phenolic, monomethoxybenzene, and methyl ketone classes. Zingerone is the pungent component of ginger. It has been reported to exist in turmeric (Alpinia officinarum), African ginger (Aframomum melegueta), and other organisms with relevant data. Zingerone is also a metabolite of Saccharomyces cerevisiae.

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- Zingerone is present in dry ginger at approximately 9.25%. It is absent in fresh ginger but is produced from gingerol or shogaols during cooking, drying, or thermal degradation via retro-aldol reaction. [1]
- Zingerone has high antioxidant activity in comparison to ascorbic acid. [1]
- Zingerone acts as a noncompetitive antagonist to 5-HT3 receptors in visceral afferent neurons, contributing to its antiemetic effect. [1]
- Zingerone enhances basal lipolysis and isoprenaline-induced lipolysis in adipocytes, and lowers blood sugar levels after oral glucose administration in ovariectomized rats. [1]
- Zingerone inhibits biofilm formation and improves the antibiofilm efficacy of ciprofloxacin against Pseudomonas aeruginosa PAO1. [1]
- Zingerone has anti-angiogenic properties via inhibition of matrix metalloproteinases (MMP-2 and MMP-9) through the JNK pathway during tumorigenesis. [1][3]
- The anti-inflammatory effect of zingerone is mediated through downregulation of NF-κB and MAPK signaling pathways. [1][2]
- In neuroblastoma patients, high expression of cell-cycle regulators (CCNB1, CCNB2, AURKA, AURKB) correlates with poor survival, suggesting zingerone's anti-mitotic effects may be therapeutically relevant. [3]

C11H14O3

194.23

194.094

C, 68.02; H, 7.27; O, 24.71

122-48-5

122-48-5

31211

Off-white to light yellow solid powder

1.1±0.1 g/cm3

323.0±27.0 °C at 760 mmHg

40-41 °C(lit.)

123.7±17.2 °C

0.0±0.7 mmHg at 25°C

1.526

0.64

1

3

4

14

191

0

O(C([H])([H])[H])C1=C(C([H])=C([H])C(=C1[H])C([H])([H])C([H])([H])C(C([H])([H])[H])=O)O[H]

OJYLAHXKWMRDGS-UHFFFAOYSA-N

InChI=1S/C11H14O3/c1-8(12)3-4-9-5-6-10(13)11(7-9)14-2/h5-7,13H,3-4H2,1-2H3

4-(4-hydroxy-3-methoxyphenyl)butan-2-one

Gingerone; Zingerone; AI331837; Vanillylacetone; AI-331837; 122-48-5; Zingiberone; 4-(4-Hydroxy-3-methoxyphenyl)butan-2-one; AI3 31837; AI3-31837

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO: 38~100 mg/mL (195.6~514.9 mM)
Water: ~10 mg/mL (~51.5 mM)
Ethanol: ~38 mg/mL (~195.6 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.87 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 (12.87 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (12.87 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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