In cancer cells, Pinocembrin targets multiple molecular pathways. It has been shown to upregulate pro-apoptotic proteins (Bax, Fas, FasL) and caspases (caspase-3, -8, -9), and downregulate mitochondrial membrane potential (ΔΨm) [1].
In the context of inflammation, Pinocembrin targets and inhibits the activation of the IκBα, JNK, and p38 MAPK signaling pathways [1].
In neuroprotection, Pinocembrin targets mitochondrial respiratory function, decreasing reactive oxygen species (ROS) and nitric oxide (NO) production, while increasing ATP content and neuronal survival rates [1].

Pinocembrin (5,7-dihydroxyflavanone) is one of the main flavonoids that have been isolated and purified using different chromatographic techniques from a variety of plants, primarily from Sparattosperma leucanthum, Eucalyptus, Populus, and Pinus heartwood, among other diverse flora. Numerous pharmacological properties, such as antimicrobial, anti-inflammatory, antioxidant, and anticancer properties, have been thoroughly studied[1]. In primary cortical neurons exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), pinocembrin has been demonstrated to increase neuronal viability, decrease lactate dehydrogenase release, inhibit the production of NO and ROS, increase glutathione levels, and downregulate the expression of neuronal NO synthase (nNOS) and iNOS[2].

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Pinocembrin demonstrated cytotoxicity against colon cancer cell lines, with IC50 values ranging from 1.6 to 13.6 μM (or 26.33 to 143.09 μg/mL) in HCT-116 and HT-29 cells. It also showed an IC50 of less than 100 ng/mL in HL-60 leukemia cells [1].
In HCT-116 colon cancer cells, Pinocembrin induced Bax-dependent mitochondrial apoptosis. This was characterized by an increase in Bax protein, a decrease in mitochondrial membrane potential, and the activation of caspase-3 and caspase-9 [1].
In HL-60 leukemia cells, Pinocembrin induced apoptosis through the upregulation of Fas and FasL, and subsequent activation of caspase-3, -8, and -9, along with tBid [1].
Pinocembrin exhibited antimicrobial activity against several bacterial strains. It inhibited 100% of the Neisseria gonorrhoeae panel at concentrations of 64 μg/mL and 128 μg/mL [1].
Pinocembrin showed antifungal activity against Penicillium italicum and Candida albicans, with a minimal inhibitory concentration (MIC) value of 100 μg/mL [1].
In SH-SY5Y neuroblastoma cells, Pinocembrin decreased glutamate-induced cell injury and protected against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced damage. It also reduced LDH release, reactive oxygen species (ROS), and nitric oxide (NO), while enhancing ATP content [1].
Pinocembrin inhibited enzymatic and non-enzymatic lipid peroxidation with IC50 values of 12.6 μM and 28 μM, respectively [1].

Pinocembrin has a broad therapeutic time window for its neuroprotective effects against cerebral ischemia injury, which may be related to its antiexcitotoxic properties[1]. It can control apoptosis, modify mitochondrial function, shield the blood-brain barrier, and lower reactive oxygen species (ROS). Astrocytic end-feet edema, neuronal apoptosis, deformation of endothelial cells and capillaries, and brain swelling may all be ameliorated by pinocembrin (10 mg/kg, i.v.). Pinocembrin inhibits ER stress and apoptosis in MCAO rats by lowering the expression of caspase-12 and C/EBP homologous protein (CHOP)/GADD153 through the PERK-elF2α-ATF4 signaling pathway. In mice, the lethal dose of intravenous pinocembrin (LD50) exceeds 700 mg/kg.

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In a mouse model of LPS-induced acute lung injury, intraperitoneal administration of Pinocembrin at 20 or 50 mg/kg significantly suppressed inflammatory responses. It downregulated the levels of TNF-α, IL-1β, and IL-6, and inhibited the activation of IκBα, JNK, and p38 MAPK signaling pathways. This led to a reduction in pulmonary edema, and decreased infiltration of neutrophils, lymphocytes, and macrophages [1].
In a rat model of cerebral ischemia, Pinocembrin alleviated brain injury. It was shown to protect mitochondrial structure and function, increase ADP/O, glutathione, and state 3 respiration, and decrease LDH release, ROS, and NO. It also enhanced ATP content in brain mitochondria [1].
In a rat model of global cerebral ischemia/reperfusion, Pinocembrin reduced brain edema, decreased neurological scores, and downregulated DNA laddering and caspase-3, while increasing PARP degradation [1].
In a study on rat hepatocarcinogenesis, administration of Pinocembrin prior to a diethylnitrosamine injection slightly increased the number of GST-P positive foci, suggesting a potential promoting effect that might be due to lipid peroxidation [1].
In an animal study on antimicrobial activity, treatment with Pinocembrin at daily doses of 100 mg/kg body weight resulted in the death of the animals between the 6th and 24th day after the start of treatment, similar to the control group [1].

Lipid Peroxidation Inhibition Assay: The anti-inflammatory activity of Pinocembrin was assessed by its ability to inhibit both enzymatic and non-enzymatic lipid peroxidation. The IC50 values for these inhibitory effects were determined to be 12.6 μM and 28 μM, respectively [1].

SH-SY5Y cells are cultured at 37°C in a humidified environment with 5% CO2 in DMEM supplemented with 10% FBS, 100 units/mL penicillin, and 100 µg/mL streptomycin. Trypsinization is used to pass cells every three to five days. Subsequently, a 96-well plate is seeded with 1 × 10⁴ cells per well, and the plate is incubated for 24 hours at 37 °C in a humidified atmosphere that contains 5% CO2. After one of the compounds is pretreated for one hour, the entire medium is replaced with fresh medium containing 1% FBS. Either 30 nM staurosporine or 2.0 µg/mL tunicamycin is then added. Assays for nuclear staining are conducted 24 hours after the initial incubation. Cell death is evaluated.

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Cytotoxicity and Apoptosis Assay in Cancer Cells: The cytotoxic effect of Pinocembrin was evaluated on colon cancer cell lines (HCT-116, HT-29) and leukemia cell lines (HL-60). Cells were treated with varying concentrations of the compound, and cell viability was measured to determine IC50 values. Apoptosis was assessed by measuring changes in mitochondrial membrane potential, Bax expression, and caspase-3/8/9 activation using techniques such as flow cytometry and western blotting [1].
Antimicrobial Susceptibility Testing: The antimicrobial activity of Pinocembrin against various Gram-positive and Gram-negative bacteria (e.g., N. gonorrhoeae, E. coli, S. aureus) was determined by measuring minimal inhibitory concentrations (MICs). The assay was performed using an adjustment of the agar streak dilution method based on radial diffusion. The concentration at which 100% of the N. gonorrhoeae strains were inhibited was recorded at 64 μg/mL and 128 μg/mL [1].
Neuroprotection Assay in SH-SY5Y Cells: To evaluate neuroprotective effects, SH-SY5Y cells were subjected to glutamate-induced injury or oxygen-glucose deprivation/reoxygenation. Cells were treated with Pinocembrin, and cell injury was assessed by measuring LDH release. Markers of oxidative stress, such as reactive oxygen species and nitric oxide levels, were also measured. Mitochondrial function was evaluated by measuring ATP content [1].

male Sprague-Dawley rats
22.5 or 67.5 mg/kg
i.v.

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LPS-Induced Acute Lung Injury Model:** To study anti-inflammatory effects, a mouse model of LPS-induced acute lung injury was used. Mice were treated with Pinocembrin at doses of 20 or 50 mg/kg via intraperitoneal injection. The administration route and frequency are implied to be i.p., but the exact timing relative to LPS challenge is not detailed in the provided text. Lung tissues and bronchoalveolar lavage fluid were collected to analyze inflammatory cell infiltration and cytokine levels (TNF-α, IL-1β, IL-6) [1].
* **Cerebral Ischemia Model (Rat):** The neuroprotective effects of Pinocembrin were evaluated in rat models of cerebral ischemia (e.g., middle cerebral artery occlusion or global cerebral ischemia/reperfusion). The specific dosing regimen, route of administration (likely intraperitoneal or intravenous), and formulation details are not provided in this review. Outcomes measured included neurological scores, brain edema, mitochondrial function, and markers of apoptosis [1].
* **Antimicrobial Toxicity Study:** In a study mentioned in the text, animals were treated with daily doses of Pinocembrin at 100 mg/kg body weight. No details on the route of administration, formulation, or dosing frequency were provided. The outcome observed was that both treated animals and controls died between the 6th and 24th day after the start of treatment [1].

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LPS-Induced Acute Lung Injury Model: To study anti-inflammatory effects, a mouse model of LPS-induced acute lung injury was used. Mice were treated with Pinocembrin at doses of 20 or 50 mg/kg via intraperitoneal injection. The administration route and frequency are implied to be i.p., but the exact timing relative to LPS challenge is not detailed in the provided text. Lung tissues and bronchoalveolar lavage fluid were collected to analyze inflammatory cell infiltration and cytokine levels (TNF-α, IL-1β, IL-6) [1].
Cerebral Ischemia Model (Rat): The neuroprotective effects of Pinocembrin were evaluated in rat models of cerebral ischemia (e.g., middle cerebral artery occlusion or global cerebral ischemia/reperfusion). The specific dosing regimen, route of administration (likely intraperitoneal or intravenous), and formulation details are not provided in this review. Outcomes measured included neurological scores, brain edema, mitochondrial function, and markers of apoptosis [1].
Antimicrobial Toxicity Study: In a study mentioned in the text, animals were treated with daily doses of Pinocembrin at 100 mg/kg body weight. No details on the route of administration, formulation, or dosing frequency were provided. The outcome observed was that both treated animals and controls died between the 6th and 24th day after the start of treatment [1].

Pinocembrin is well metabolized and absorbed after oral administration [2].
It can pass through the blood-brain barrier (BBB) in a passive transport process, which is partly conducted by p-glycoprotein [2].
In a preclinical study, rats were administered pinocembrin at 22.5 mg/kg or 67.5 mg/kg via intravenous injection. Reversed-phase high-performance liquid chromatography with ultraviolet detection was used to measure plasma concentrations [2].
In another study, rats were injected intravenously with 10 mg/kg pinocembrin. High-performance liquid chromatographic-electrospray ionization-mass spectrometry was used to detect S-pinocembrin and R-pinocembrin in plasma [2].
In clinical trials, high-performance liquid chromatography-mass spectrometry/mass spectrometry has been used to measure pinocembrin in the plasma of healthy volunteers [2].

Pinocembrin is noted to have relatively less toxicity toward normal human umbilical cord endothelial cells compared to its cytotoxicity against cancer cells [1].
In a rat hepatocarcinogenesis study, Pinocembrin slightly increased the number of GST-P positive foci when given prior to a carcinogen, suggesting a potential promoting effect that might be due to lipid peroxidation [1].
In an antimicrobial study, treatment with Pinocembrin at daily doses of 100 mg/kg body weight resulted in the death of the animals between the 6th and 24th day after the start of treatment, similar to the control group, indicating that this dose did not cause additional acute toxicity beyond the control conditions [1].

[1]. Biomed Res Int . 2013:2013:379850.

[2]. Mol Neurobiol . 2016 Apr;53(3):1794-1801.

[3]. J Pharm Biomed Anal . 2009 Jul 12;49(5):1277-81.

[4]. J Agric Food Chem . 2008 Oct 8;56(19):8944-53.

It has been reported that 5,7-dihydroxyflavanone is found in bees, turmeric, and other organisms with relevant data. See also: Pinus spp. (Note moved to...)

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Background: Pinocembrin (5,7-dihydroxyflavanone) is a primary flavonoid isolated from various plants, including Pinus heartwood, Eucalyptus, Populus, honey, propolis, and many others. It is known for its versatile pharmacological activities [1].
Mechanism of Action (Summary): Pinocembrin exerts its effects through multiple mechanisms. Its anticancer activity is linked to the induction of mitochondrial apoptosis via Bax and caspase activation. Its anti-inflammatory effects are mediated through the suppression of the IκBα, JNK, and p38 MAPK pathways, leading to reduced cytokine production. Its neuroprotective effects are associated with preserving mitochondrial function, reducing oxidative stress, and inhibiting excitotoxicity [1].
Biosynthesis: Pinocembrin can be produced biosynthetically in engineered E. coli by assembling an artificial phenylpropanoid pathway containing genes from yeast, actinomycetes, and plants [1].
Therapeutic Potential: The compound is considered a promising pharmacological candidate with potential applications in treating inflammation, cancer, neurodegenerative diseases, and microbial infections. However, further studies and clinical trials are required to fully understand its mechanisms and validate its medical applications [1].

C15H12O4

256.25

256.074

C, 70.31; H, 4.72; O, 24.97

68745-38-0

68745-38-0

238782

White to off-white solid powder

1.386g/cm3

520.6ºC at 760 mmHg

202-203ºC

203.3ºC

1.85E-11mmHg at 25°C

1.661

2.804

2

4

1

19

337

0

Oc1cc(O)c2C(=O)CC(Oc2c1)c1ccccc1

URFCJEUYXNAHFI-UHFFFAOYSA-N

InChI=1S/C15H12O4/c16-10-6-11(17)15-12(18)8-13(19-14(15)7-10)9-4-2-1-3-5-9/h1-7,13,16-17H,8H2

5,7-dihydroxy-2-phenyl-2,3-dihydrochromen-4-one

DL-0108; DL0108; DL 0108; Pinocembrin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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