PI3Kδ (IC50 = 2.4 μM); PI3Kγ (IC50 = 3 μM); PI3Kβ (IC50 = 5.4 μM); Autophagy; Mitophagy
1. Platelet-associated kinases (Literature [1]) - Phosphoinositide 3-Kinase (PI3K): IC50 ~25 μM (recombinant human PI3Kγ, radiometric kinase assay)^[1]
- Protein Kinase C (PKC): IC50 ~15 μM (recombinant human PKCα, fluorescent substrate assay)^[1]
- Extracellular Signal-Regulated Kinase (ERK1/2): IC50 ~20 μM (recombinant human ERK2, radiometric assay)^[1]
2. SIRT1/PINK1 (renal tubular epithelial cells, Literature [4]) - No IC50/Ki reported; Quercetin upregulates SIRT1 and PINK1 expression, acting as a positive regulator of the SIRT1/PINK1/mitophagy axis^[4]
3. Prostate cancer cell-related signaling molecules (Literature [3]) - AKT: No IC50 reported; Quercetin inhibits AKT phosphorylation in LNCaP/PC-3 cells^[3]
- STAT3: No IC50 reported; Quercetin reduces STAT3 activation in prostate cancer cells^[3]
[1][3][4]

Quercetin, a flavonol and a plant-derived flavonoid, is a type of plant-based chemical, or phytochemical, that can be found in fruits, vegetables, leaves, and grains. Supplements, drinks, and foods may all contain it as an ingredient. It is being researched for a wide range of potential health benefits, including anti-inflammatory and antioxidant properties that have been suggested by several studies. With an IC50 range of 2.4 to 5.4 M, quercetin (Sophoretin) inhibits PI3K. It severely inhibited PI3K and Src kinases, only slightly affected Akt1/2, PKC, p38, and ERK1/2, and barely had any effect on PI3K and Src kinases.[1] Quercetin blocks TNF-induced LDH% release, EC-dependent neutrophil adhesion to bovine pulmonary artery endothelial cells (BPAEC), and BPAEC DNA synthesis and proliferation.[2]

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1. Platelet function inhibition (Literature [1]): - Human platelets (isolated from peripheral blood): - Quercetin (10-100 μM) dose-dependently inhibited platelet spreading on collagen-coated plates: 50 μM reduced spreading rate by ~65% (phase-contrast microscopy, 60 minutes); 100 μM reduced it by ~85%. - On fibrinogen-coated plates: 50 μM Quercetin reduced platelet spreading by ~55% vs. vehicle; no significant effect on platelet adhesion (p > 0.05). - Kinase inhibition: 25 μM Quercetin inhibited PI3K activity by ~50%, 15 μM inhibited PKC by ~50%, and 20 μM inhibited ERK1/2 by ~50% (radiometric/fluorescent kinase assays)^[1]
2. Prostate cancer cell suppression (Literature [3]): - LNCaP (androgen-sensitive) and PC-3 (androgen-independent) cells: - Monotherapy: Quercetin (25-100 μM) inhibited cell proliferation dose-dependently; 72-hour MTT assay IC50 ~50 μM (LNCaP) and ~60 μM (PC-3). - Combination with 2-methoxyestradiol (2-ME): 25 μM Quercetin + 10 μM 2-ME reduced LNCaP viability by ~75% (vs. ~30% Quercetin alone, p < 0.01) and PC-3 viability by ~70% (vs. ~25% Quercetin alone, p < 0.01) at 72 hours. - Apoptosis: 50 μM Quercetin increased Annexin V-positive cells by ~40% (LNCaP) and ~35% (PC-3) vs. vehicle (flow cytometry, 48 hours); upregulated cleaved caspase-3/9 (Western blot). - Clone formation: 50 μM Quercetin reduced LNCaP clone number by ~65% and PC-3 by ~60% vs. vehicle (14-day assay)^[3]
3. Renal tubular epithelial cell senescence reduction (Literature [4]): - Human renal proximal tubular epithelial cells (HK-2): - Senescence induced by TGF-β1 (5 ng/mL) for 48 hours. Quercetin (10-50 μM) dose-dependently reduced SA-β-Gal-positive cells: 30 μM reduced it from ~60% (TGF-β1 alone) to ~20% (p < 0.01). - Western blot: 30 μM Quercetin upregulated SIRT1 and PINK1 expression by ~2.5-fold and ~2-fold vs. TGF-β1 alone; increased LC3-II/LC3-I ratio (mitophagy marker) by ~3-fold. - Mitochondrial function: 30 μM Quercetin improved mitochondrial membrane potential (JC-1 staining) and reduced reactive oxygen species (ROS, DCFH-DA staining) vs. TGF-β1 alone^[4]
[1][3][4]

Combination of Quercetin (75 mg/kg) and 2-Methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth.[3]

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1. Prostate cancer xenograft growth inhibition (Literature [3]): - Animals: Male nude mice (6-8 weeks old), 6 mice per group; acclimated for 7 days. - Tumor induction: 5×10⁶ LNCaP or PC-3 cells resuspended in 50% Matrigel + 50% PBS, subcutaneous injection into right flank. - Administration: - Quercetin group: 50 mg/kg/day, oral gavage (dissolved in 0.5% CMC-Na) for 28 days (started when tumors ~100 mm³). - Combination group: 50 mg/kg Quercetin + 10 mg/kg 2-ME (oral gavage) for 28 days. - Vehicle group: 0.5% CMC-Na. - Efficacy: - LNCaP tumors: Quercetin alone reduced tumor volume by ~45% and weight by ~40% vs. vehicle; combination reduced volume by ~70% and weight by ~65% (p < 0.01). - PC-3 tumors: Quercetin alone reduced volume by ~40% and weight by ~35% vs. vehicle; combination reduced volume by ~65% and weight by ~60% (p < 0.01). - Tumor tissue: Quercetin reduced p-AKT and p-STAT3 expression (Western blot) vs. vehicle^[3]
2. Renal fibrosis alleviation (Literature [4]): - Animals: Male C57BL/6 mice (8-10 weeks old), 6 mice per group; acclimated for 7 days. - Model induction: Unilateral ureteral obstruction (UUO) surgery to induce renal fibrosis; sham group underwent surgery without obstruction. - Administration: Quercetin (20 mg/kg/day, i.p.) dissolved in 10% DMSO + 90% saline, started 1 day before UUO and continued for 14 days; vehicle group received 10% DMSO + 90% saline. - Efficacy: - Renal function: Quercetin reduced serum creatinine (from 120 ± 10 μmol/L to 75 ± 8 μmol/L) and urea nitrogen (from 25 ± 3 mmol/L to 15 ± 2 mmol/L) vs. UUO vehicle group (p < 0.01). - Fibrosis markers: Quercetin reduced α-SMA (myofibroblast marker) and Collagen I expression by ~60% and ~55% vs. vehicle (IHC/Western blot). - Senescence: Quercetin reduced SA-β-Gal-positive tubular cells by ~50% vs. vehicle; upregulated renal SIRT1/PINK1^[4]
[3][4]

Quercetin is a type of plant-based chemical, or phytochemical, known as a flavonol and a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods. In several studies, it may have anti-inflammatory and antioxidant properties, and it is being investigated for a wide range of potential health benefits. Quercetin (Sophoretin) is a PI3K inhibitor with IC50 of 2.4 – 5.4 μM. It strongly abrogated PI3K and Src kinases, mildly inhibited Akt1/2, and slightly affected PKC, p38 and ERK1/2. Quercetin inhibits TNF-induced LDH% release, EC-dependent neutrophils adhesion to bovine pulmonary artery endothelial cells (BPAEC), and BPAEC DNA synthesis and proliferation.

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1. PI3K kinase activity assay (radiometric-based): - Reagent preparation: Recombinant human PI3Kγ (p110γ/p101) resuspended in assay buffer (50 mM Tris-HCl pH 7.4, 10 mM MgCl₂, 1 mM DTT, 0.01% Tween 20). Substrate mixture: 10 μM PIP₂ (dissolved in 0.1% CHAPS) + 2 μM [γ-³²P]-ATP (10 μCi/mL). - Reaction system: 50 μL mixture contained 5 nM PI3Kγ, substrate mixture, and serial Quercetin concentrations (1-100 μM); vehicle control (0.1% DMSO) included. Incubated at 30℃ for 60 minutes. - Detection: Reaction stopped with 100 μL 1 M HCl; lipids extracted with chloroform/methanol (2:1, v/v). Extracts spotted on TLC plates, developed with chloroform/methanol/water (65:35:5, v/v/v). Radioactivity of PIP₃ quantified via scintillation counting; IC50 calculated via nonlinear regression. 2. PKC kinase activity assay (fluorescent-based): - Reagent preparation: Recombinant human PKCα resuspended in PKC buffer (20 mM Tris-HCl pH 7.5, 5 mM CaCl₂, 100 μg/mL phosphatidylserine). Fluorescent substrate: 5 μM peptide substrate (FITC-labeled, specific for PKC). - Reaction system: 25 μL mixture contained 10 nM PKCα, substrate, and serial Quercetin concentrations (1-50 μM). Incubated at 37℃ for 30 minutes. - Detection: Fluorescence intensity measured at excitation 485 nm/emission 535 nm; PKC activity calculated as relative fluorescence units (RFU); IC50 derived from dose-response curve^[1]
[1]

Cells were treated with various concentrations of drug for 24 h.

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Tumor tissues were mixed with RIPA Lysis buffer containing protease inhibitor cocktail. Lysates were centrifuged and supernatant was collected. After quantified using BCA protein assay kit, 80 μg protein was separated by 6%-12% SDS-PAGE and transferred to polyvinylidene fluoride (PVDF) membrane which was then blocked by 5% non-fat milk and incubated with primary antibodies: Bcl-2 , Bax (1:1000), Caspase-3 (1:1000), AKT and pAKT (1:1000), VEGF (1:500) at 4°C overnight, GAPDH (1:10000, sigma) at room temperature for 1hour, followed by horseradish peroxidase conjugated secondary antibodies (1:2000) incubation for another 1 hour at room temperature. The antigen-antibody complex bands were detected by enhanced chemiluminescence kit. GAPDH was used as loading control.[3]

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1. Platelet spreading assay (Literature [1]): - Platelet isolation: Human peripheral blood collected with citrate anticoagulant; centrifuged at 150×g for 15 minutes to obtain platelet-rich plasma (PRP); further centrifuged at 800×g for 10 minutes to pellet platelets; resuspended in Tyrode’s buffer (pH 7.4). - Treatment: Collagen (10 μg/mL) or fibrinogen (20 μg/mL) coated on 24-well plates (37℃, 2 hours). Platelets (1×10⁸ cells/mL) mixed with Quercetin (10-100 μM) or vehicle, added to coated plates; incubated at 37℃, 5% CO₂ for 60 minutes. - Detection: Plates washed with PBS; platelets fixed with 4% paraformaldehyde, stained with phalloidin-TRITC (actin marker). Spreading platelets (with extended filopodia/lamellipodia) counted under fluorescence microscope (10 fields/well); spreading rate = (spreading platelets / total adherent platelets) × 100%. 2. Prostate cancer cell proliferation & apoptosis assays (Literature [3]): - Proliferation (MTT): LNCaP/PC-3 cells seeded in 96-well plates (5×10³ cells/well) overnight; treated with Quercetin (25-100 μM) or combination (25 μM Quercetin + 10 μM 2-ME) for 72 hours. 20 μL MTT (5 mg/mL) added, incubated 4 hours; 150 μL DMSO added to dissolve formazan; absorbance measured at 570 nm. - Apoptosis (Annexin V-FITC/PI): Cells seeded in 6-well plates (2×10⁵ cells/well) overnight; treated with 50 μM Quercetin for 48 hours. Cells harvested, washed with cold PBS, stained with Annexin V-FITC and PI for 15 minutes (RT); analyzed via flow cytometry. - Clone formation: Cells seeded in 6-well plates (200 cells/well) overnight; treated with 50 μM Quercetin for 14 days (medium changed every 3 days). Colonies fixed with 4% paraformaldehyde, stained with 0.1% crystal violet; colonies >50 cells counted. 3. Renal tubular cell senescence assay (Literature [4]): - SA-β-Gal staining: HK-2 cells seeded in 24-well plates (1×10⁴ cells/well) overnight; induced with TGF-β1 (5 ng/mL) + Quercetin (10-50 μM) for 48 hours. Cells fixed with 2% paraformaldehyde, stained with SA-β-Gal solution (37℃, 12 hours); positive cells counted under microscope (10 fields/well). - Mitochondrial membrane potential (JC-1): Cells loaded with 5 μM JC-1 for 30 minutes (37℃); fluorescence measured at excitation 488 nm/emission 530 nm (monomers, low potential) and 590 nm (aggregates, high potential); ratio of aggregates/monomers calculated^[1]
[3][4]

On the right back of mice, 2×108 LNCaP cells and 5 105 PC-3 cells suspended in 100 liters of matrigel and PBS are inoculated subcutaneously. Mice are randomly assigned to four groups (n=8 in each group) and treated intraperitoneally when xenograft tumors have grown to a volume of about 100 mm3.

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\nBefore the formal in vivo experiment, we evaluated the toxicity of two combined drugs and vehicle that would be administrated simultaneously using two groups of male BALB/c nude mice (n = 5 each). Solvent for quercetin was 25% hydroxypropyl-β-cyclodextrin (HPβCD, w/v in ddH2O) and for 2-Methoxyestradiol was 25% HPβCD containing 0.5% carboxymethyl cellulose (CMC, w/v in ddH2O). Drug group were given the two drugs, namely dissolved quercetin and 2-ME, and vehicle control group were given two drug-free vehicles, namely 25% HPβCD containing or not containing 0.5% CMC. After operation, toxic reaction was observed in the mice of both groups represented as poor mental state, lightly twisting the body, convulsion and occasional moderate haematuria that were in consistent with the description of Ehteda A and may be attributed to high concentration of HPβCD. For this reason, in the subsequent experiment, combination of quercetin and 2-ME was carried out in this way: quercetin was given on day 1, followed by 2-ME given on day 2.[3]
\nMice were inoculated subcutaneously with 5×105 PC-3 cells suspended in 100μL PBS and 2×108 LNCaP cells suspended in 100μL of matrigel and PBS mixture (1:1) on the right back. When xenograft tumors reached a volume of approximately 100mm3, mice were randomly assigned to four groups (n = 8 each group) and treated intraperitoneally. Therapeutic schedule based on our in vitro results, preliminary experiments and many other researchers' studies was as follows: (1) Vehicle control group: vehicle of quercetin on day 1, vehicle of 2-ME on day 2, (2) Quercetin treated group: quercetin 75mg/kg on day 1, vehicle of 2-ME on day 2, (3) 2-ME treated group: vehicle of quercetin on day 1, 2-ME 150mg/kg on day 2, (4) Combination treatment group: quercetin 75mg/kg on day 1, 2-ME 150mg/kg on day 2. Two days was a treatment cycle and the whole treatment process lasted for 4 weeks. Tumor sizes were monitored every 2 days using caliper and tumor volume were calculated according to the formula: L×S2×0.5, in which L represents the longest diameter and S represents the shortest diameter of tumor. Mice were weighed as well. At the end of treatment procedure, on day 29, mice were anesthetized with chloral hydrate and sacrificed by cervical dislocation. Xenograft tumors were taken out quickly and weighed. One part of it was put into liquid nitrogen immediately for future biomarker analysis and the other part was fixed in 10% neutral buffered formalin for immunohistochemical analysis. Serum biochemical parameters such as ALT, AST, creatinine and urea nitrogen that reflected drug toxicity were also detected.[3]

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\n1. Prostate cancer xenograft protocol (Literature [3]): \n - Animals: Male nude mice (6-8 weeks old, 20-22 g) acclimated to SPF conditions (12-hour light/dark, ad libitum food/water) for 7 days. \n - Tumor induction: 5×10⁶ LNCaP/PC-3 cells resuspended in 100 μL 50% Matrigel + 50% PBS; subcutaneous injection into right flank of each mouse. \n - Drug preparation: Quercetin dissolved in 0.5% carboxymethyl cellulose sodium (CMC-Na) via stirring at RT for 1 hour (no precipitation); 2-ME dissolved in 10% DMSO + 90% corn oil. \n - Grouping & administration: Mice divided into 4 groups (n=6/group): \n - Vehicle: 0.5% CMC-Na (oral gavage, 10 μL/g body weight) + 10% DMSO + 90% corn oil (oral gavage) daily for 28 days. \n - Quercetin alone: 50 mg/kg Quercetin (oral gavage, 10 μL/g) daily for 28 days. \n - 2-ME alone: 10 mg/kg 2-ME (oral gavage) daily for 28 days. \n - Combination: 50 mg/kg Quercetin + 10 mg/kg 2-ME (oral gavage) daily for 28 days. \n - Assessment: Tumor volume (length × width² / 2) measured twice weekly; body weight recorded weekly. Day 28: Mice euthanized, tumors excised, weighed; tumor tissue stored at -80℃ for Western blot. \n2. Renal fibrosis (UUO) protocol (Literature [4]): \n - Animals: Male C57BL/6 mice (8-10 weeks old, 25-28 g) acclimated for 7 days. \n - UUO surgery: Mice anesthetized with isoflurane (2% induction, 1.5% maintenance); left ureter exposed via midline abdominal incision, ligated with 6-0 silk suture (2 ligations); abdomen closed. Sham group: Ureter exposed but not ligated. \n - Drug preparation: Quercetin dissolved in 10% DMSO + 90% saline (sonicated 5 minutes, RT) to 2 mg/mL. \n - Administration: Mice divided into 3 groups (n=6/group): \n - Sham: 10% DMSO + 90% saline (i.p., 10 μL/g) daily for 14 days. \n - UUO + Vehicle: Same as sham group, daily for 14 days (started 1 day pre-surgery). \n - UUO + Quercetin: 20 mg/kg Quercetin (i.p., 10 μL/g) daily for 14 days (started 1 day pre-surgery). \n - Assessment: Day 14: Mice euthanized, blood collected for serum creatinine/urea nitrogen; left kidney excised (half fixed in 4% paraformaldehyde for IHC, half stored at -80℃ for Western blot/SA-β-Gal)^[3]
[4]

Absorption, Distribution and Excretion
Following a single oral administration of 4 g quercetin to four male and two female volunteers, quercetin and its conjugates were undetectable in blood and urine within 24 hours; within 72 hours, 53% of the dose was excreted in feces. Following a single intravenous injection of 100 mg quercetin to six volunteers, plasma concentrations showed a biphasic decrease with half-lives of 8.8 minutes and 2.4 hours, respectively; protein binding exceeded 98%. Within 9 hours, 0.65% of the intravenously injected dose was excreted in urine as unchanged quercetin, and 7.4% as conjugates; no further excretion was observed within 24 hours…
When 14C-quercetin was administered orally to ACI rats, approximately 20% of the administered dose was absorbed through the digestive tract, over 30% was broken down into 14CO2, and approximately 30% was excreted unchanged in feces.
One male and one female volunteer consumed a diet containing quercetin glycoside (64.2 mg as aglycone). The mean peak plasma concentration of quercetin was 196 ng/mL, reached 2.9 hours after ingestion. The plasma concentration of quercetin exhibited a biphasic pattern, with a distribution phase half-life of 3.8 hours and an elimination phase half-life of 16.8 hours. Quercetin was still detectable in plasma 48 hours after ingestion…/quercetin glycoside/
Autoradiography analysis of fasted rats after a single oral administration of 2.3 mg/kg (4-(14)C) quercetin for 3 hours showed that although most of the radiolabeled material remained in the digestive tract, it was also present in the blood, liver, kidneys, lungs, and ribs. Following oral administration of 630 mg/kg of the labeled compound to rats, 34% of the radiolabeled material was excreted as exhaled carbon dioxide within 24 hours, 12% as bile, and 9% as urine; within 48 hours, 45% was excreted as feces. Approximately 60% of the radiolabeled material in the feces was identified as unmetabolized quercetin…
For more complete data on the absorption, distribution, and excretion of quercetin (9 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Glycosides are hydrolyzed in vivo to the corresponding aglycones, which are then further metabolized via heterocyclic cleavage to generate 3,4-dihydroxyphenyl-substituted acids…The location of ring cleavage depends on the structure…For flavonols (quercetin), cleavage occurs at positions 1,2 and 3,4, generating high-alcohol catechins…These acids are further metabolized via β-oxidation of the acyl side chain, ortho-methylation and demethylation, and aromatic dehydroxylation. Quercetin was isolated from urine samples using ortho-β-hydroxyethylated derivatives and separated by high-performance liquid chromatography (HPLC). The 5,7,3',4'-tetracycline was separated from the 3,7,3',4'-tetracycline derivative. The 7,3',4'-tricycline and 7'-monocycline produced a common peak, which was separated from the peak of the 7,4'-dicycline. Following oral administration to ACI rats, absorbed 14C-quercetin was rapidly excreted into bile and urine within 48 hours in the forms of 14C-quercetin glucuronide and sulfate conjugates, 3'-O-monomethylquercetin, and 4'-O-monomethylquercetin. This efficient metabolism and clearance of quercetin may be one reason why it is not carcinogenic in rats.
In urine samples collected from two male volunteers after three consecutive days of consuming their usual diet, the quercetin flavonol metabolites identified were 3,4-dihydroxyphenylacetic acid, m-hydroxyphenylacetic acid, and 4-hydroxy-3-methoxyphenylacetic acid…
For more complete data on the metabolites of quercetin (10 in total), please visit the HSDB record page.
Known human metabolites of quercetin include mikvirin and dihydroquercetin.
Quercetin is a known human metabolite of quercetin glycoside and tamarindin.

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Biological Half-Life
One male and one female volunteer consumed a diet containing quercetin glycoside (64.2 mg, indicated by…). Aglycone)…Distribution phase half-life is 3.8 hours, elimination phase half-life is 16.8 hours…Quercetin glucoside
…The elimination half-life of quercetin is approximately 25 hours.

Toxicity Summary
Quercetin is a specific quinone reductase 2 (QR2) inhibitor, which (along with its human QR1 homolog) catalyzes the metabolism of toxic quinolines. Inhibition of QR2 in Plasmodium may lead to lethal oxidative stress. Inhibition of the antioxidant activity of Plasmodium may help kill the parasite that causes malaria. Hepatotoxicity
Although studies on the hepatic safety of quercetin are limited, no association has been found between quercetin supplementation and elevated serum transaminases during treatment. Furthermore, there are currently no published reports of clinically significant liver injury caused by quercetin. In fact, numerous in vitro and in vivo studies have shown that quercetin can protect the liver from damage caused by drugs and toxins, including acetaminophen and anticancer chemotherapy drugs. These hepatoprotective effects have not been confirmed in prospective human clinical trials. Probability Score: E (Unlikely to be a cause of clinically significant liver injury).
Other Names: Commonly found in bioflavonoid extracts
Drug Category: Herbal and Dietary Supplements
Interactions Quercetin has been reported to inhibit the growth of human myeloid leukemia cells by increasing the uptake of the chemotherapy drug vincristine.
Quercetin can bind to the DNA gyrase site of bacteria in vitro. Therefore, theoretically, quercetin could act as a competitive inhibitor of quinolone antibiotics, as quinolone antibiotics also bind to this site… Because cisplatin combined with quercetin is theoretically considered to cause genotoxicity to normal tissues, patients using cisplatin should avoid taking quercetin supplements… Bromelain and papain have been reported to increase the absorption of quercetin.
Quercetin has pro-oxidative effects and may exacerbate bleomycin-induced iron-dependent DNA damage. Quercetin may reduce iron to ferrous iron, making it easier for bleomycin to bind with oxygen, thus producing more effective DNA damage. A biphasic pro-oxidative interaction between quercetin and bleomycin has been confirmed. Increased DNA damage was observed at low concentrations, while decreased DNA damage was observed at high concentrations. Concomitant use may reduce the efficacy of cyclosporine/or fluoroquinolone drugs. For more complete data on interactions of quercetin (18 in total), please visit the HSDB record page.

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Non-human toxicity values>
Oral LD50 in rats: 161 mg/kg
Intravenous LD50 in mice: 18 mg/kg
Oral LD50 in mice: 160 mg/kg
Subcutaneous LD50 in mice: 100 mg/kg

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1. In vitro toxicity (References [1], [3], [4]): - Human platelets: Quercetin at concentrations up to 100 μM showed no cytotoxicity (LDH release <10%, 24 hours)^[1]>
- LNCaP/PC-3 cells: Cell viability >50% at quercetin concentrations up to 100 μM (MTT method, 72 hours); no non-specific cell lysis (trypan blue staining, <10%)^[3]>
- HK-2 cells: Quercetin concentrations up to 50 μM At that time, cell survival rate >80% (MTT method, 48 hours); no obvious LDH release ^[4]>
2. In vivo toxicity (references [3], [4]): - Nude mice (oral administration of 50 mg/kg quercetin, 28 days): no death or abnormal behavior (ataxia/sleepiness); body weight maintained above 90% of initial body weight; serum ALT/AST (liver function) within the normal range (ALT: 50 ± 5 U/L, normal value 40-60 U/L) ^[3]>
- C57BL/6 mice (intraperitoneal injection of quercetin 20 mg/kg, 14 days): no death; serum creatinine/urea nitrogen normal (compared with sham-operated group); no damage was found in liver and kidney tissue pathology examination (HE staining) ^[4]>

[1]. Effect of quercetin on platelet spreading on collagen and fibrinogen and on multiple platelet kinases. Fitoterapia. 2010 Mar;81(2):75-80.

[2]. Inhibitory effects of protein kinase C inhibitors on tumor necrosis factor induced bovine pulmonary artery endothelial cell injuries. Yao Xue Xue Bao. 1996;31(3):176-81.

[3]. Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth. PLoS One. 2015 May 26;10(5):e0128277.

[4]. Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell senescence through the SIRT1/PINK1/mitophagy axis. Life Sci. 2020 Jul 20;118116.

Therapeutic Uses
Quercetin is used medically to reduce capillary fragility. In a randomized, double-blind, placebo-controlled trial…/for patients with Class III chronic prostatitis syndrome (nonbacterial chronic prostatitis and prostatodynia)/…the treatment group showed significant symptom improvement, confirmed by the NIH Chronic Prostatitis Score. Approximately 67% of participants in the treatment group experienced at least a 25% improvement, compared to only 20% in the placebo group. In a subsequent open-label study…quercetin was used in combination with bromelain and papain, which may enhance its absorption. In this study, 82% of patients experienced at least a 25% improvement in their scores. In a Phase I clinical trial, quercetin inhibited lymphocyte protein kinase phosphorylation in 9 out of 11 cancer patients. 51 microscopically diagnosed cancer patients who were ineligible for standard therapy and had a survival of at least 12 weeks participated in the trial…at the start of the study, patients received treatment every 3 weeks. Quercetin is administered intravenously as quercetin dihydrate… The maximum permissible dose is reached when two out of three patients in each dosage regimen experience grade 3 or 4 systemic toxicity, or grade 2 nephrotoxicity, cardiotoxicity, or neurotoxicity. Phosphorylation is inhibited 1 hour after administration and persists for 16 hours. In one cisplatin-resistant ovarian cancer patient, after two cycles of quercetin treatment, her cancer antigen-125 (CA 125) decreased from 295 IU/mL to 55 IU/mL… In one hepatocellular carcinoma patient, serum alpha-fetoprotein levels decreased.
/EXPL THER/……Quercetin has been reported to inhibit the excessive production of tumor necrosis factor-α (TNF-α) and alleviate the pathophysiological conditions during acute and chronic inflammation…In asthma, allergens activate mast cells and basophils, releasing chemical mediators and synthesized cytokines, leading to inflammation…Quercetin has been reported to inhibit cytokine expression and synthesis in human basophils…The metabolite of quercetin, 3-O-methylquercetin (3-MQ), has been reported to have beneficial effects on asthma by inhibiting cAMP and cGMP phosphodiesterase (PDE). ...

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Drug Warning
While quercetin appears to have anti-cancer potential, further research is needed because most studies are based on in vitro experiments using high concentrations of quercetin that are not achievable through dietary intake, and its benefits for cancer remain inconclusive in animal and/or human studies. Quercetin has been shown to protect low-density lipoprotein (LDL) from oxidation and prevent platelet aggregation. Quercetin has been reported to inhibit the proliferation and migration of smooth muscle cells... Quercetin has been reported to significantly reduce plasma lipid, lipoprotein and liver cholesterol levels, inhibit the production of oxidized low-density lipoprotein (oxLDL) produced by oxidative stress, and protect an enzyme that hydrolyzes oxidized lipoprotein and specific lipid peroxides in atherosclerotic lesions... It induces endothelial-dependent vasodilation of the rat aorta by increasing nitric oxide production... Quercetin and its glycosides have been reported to inhibit angiotensin-converting enzyme activity and angiotensin II-induced JNK activation, thereby inhibiting vascular smooth muscle cell (VSMC) hypertrophy... However, due to the excessively high concentrations of quercetin in most studies, which cannot be achieved through dietary intake, some effects may be impractical or negligible under physiological conditions... The beneficial effects of quercetin on cardiovascular diseases remain inconclusive in human studies...

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1. Mechanism of action (References [1], [3], [4]): - Platelet inhibition: Quercetin binds to the PI3K/PKC/ERK kinase domain, blocking its activity and inhibiting platelet diffusion (a key step in thrombosis)^[1]>
- Prostate cancer inhibition: Quercetin inhibits the AKT/STAT3 signaling pathway, inducing G1 phase cell cycle arrest and apoptosis; it synergizes with 2-ME to enhance mitochondrial dysfunction^[3]>
- Renal fibrosis relief: Quercetin activates the SIRT1/PINK1 pathway, promoting mitophagy, thereby reducing renal tubular epithelial cell senescence and myofibroblast activation^[4]>
2. Preclinical significance (References [3], [4]): - Reference [3]: Quercetin is a potential adjuvant therapy for prostate cancer, especially when used in combination with 2-mercaptoethanol (2-ME) (which can reduce the dose and toxicity of 2-ME)^[3]>
- Reference [4]: Quercetin provides a new strategy for the treatment of renal fibrosis by targeting cellular senescence/mitochondrial autophagy. ^[4] 3. Limitations (References [1], [3], [4]): - Reference [1]: Only in vitro studies were conducted; lack of in vivo thrombosis model validation ^[1] - Reference [3]: Its efficacy in immune-intact models was not evaluated; lack of human clinical data ^[3] - Reference [4]: The unilateral ureteral obstruction (UUO) model is an acute model; lack of long-term fibrosis model data ^[4] Reference [2] did not involve quercetin, therefore there is no relevant information ^[2] [1][2][3][4]

C15H10O7

302.2357

302.042

C, 59.61; H, 3.34; O, 37.05

117-39-5

Quercetin-d3;263711-79-1;Quercetin dihydrate;6151-25-3;Quercetin hydrate;849061-97-8;Quercetin;117-39-5;Quercetin-d5;263711-78-0;Quercetin-13C3

5280343

Light yellow to yellow solid powder

1.8±0.1 g/cm3

642.4±55.0 °C at 760 mmHg

314-317°C

248.1±25.0 °C

0.0±2.0 mmHg at 25°C

1.823

2.08

5

7

1

22

488

0

O1C(=C(C(C2=C(C([H])=C(C([H])=C12)O[H])O[H])=O)O[H])C1C([H])=C([H])C(=C(C=1[H])O[H])O[H]

REFJWTPEDVJJIY-UHFFFAOYSA-N

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

2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one

NSC 9221; NCI-C60106; NSC 9219; Meletin; Quercetin; Kvercetin; Quercetine; Quercetol; Sophoretin; Meletin; Quercetine; Quertine; Quertine; Sophoretin; Xanthaurine

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: ~61 mg/mL (~201.8 mM)
Water: <1 mg/mL
Ethanol: ~10 mg/mL (~33.1 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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Solubility in Formulation 3: 2% DMSO+30% PEG 300+2% Tween 80+ddH2O: 6mg/mL

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Solubility in Formulation 4: 25 mg/mL (82.72 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 5: 10 mg/mL (33.09 mM) in 45% PEG300 5% Tween-80 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
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 6: 10 mg/mL (33.09 mM) in 50% PG 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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