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| Other Sizes |
| Targets |
Hesperetin activates p38 MAPK to induce apoptosis in glioblastoma cells.
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| ln Vitro |
- Antiproliferative Activity and Apoptosis Induction:
- Reference [4]: Hesperetin significantly inhibited the proliferation of U87 and T98G glioblastoma cells, with IC50 values of 25 μM and 30 μM, respectively. Treatment with Hesperetin (20–40 μM) for 24 hours induced apoptosis, as confirmed by Annexin V/PI staining (the apoptosis rate in U87 cells increased from 8% to 35%) and caspase-3 activation. Western blot analysis revealed dose-dependent phosphorylation of p38 MAPK, upregulation of the pro-apoptotic protein Bax, and downregulation of the anti-apoptotic protein Bcl-2.
- Reference [2]: Hesperetin inhibited human UDP-glucuronosyltransferase (UGT) enzymes in a concentration-dependent manner. The IC50 values were 12.3 μM for UGT1A1, 8.7 μM for UGT1A4, 15.6 μM for UGT1A6, 9.2 μM for UGT1A9, and 18.4 μM for UGT2B7. Kinetic analysis indicated competitive inhibition for UGT1A1 and non-competitive inhibition for UGT1A4. |
| ln Vivo |
- Neuroprotective Effect:
- Reference [3]: Oral administration of Hesperetin (50 mg/kg) significantly attenuated cadmium-induced oxidative stress in rat brains. Compared with cadmium-exposed controls, Hesperetin treatment reduced malondialdehyde (MDA) levels by 40% and increased superoxide dismutase (SOD) activity by 35%. Immunohistochemical analysis showed decreased nuclear translocation of NF-κB p65 and increased Nrf2 expression in the hippocampus.
- Reference [1]: Co-delivery of Hesperetin (100 mg/kg) with bicalutamide (50 mg/kg) via a self-nanoemulsifying drug delivery system (SNEDDS) reduced bicalutamide-induced hepatotoxicity in rats. Specifically, alanine transaminase (ALT) and aspartate transaminase (AST) levels were normalized, with reductions of 55% and 60%, respectively, compared to the group treated with bicalutamide alone. Additionally, the SNEDDS formulation improved the oral bioavailability of Hesperetin by 2.3-fold. |
| Enzyme Assay |
- UGT Enzyme Inhibition Assay:
- Reference [2]: Recombinant UGT enzymes (0.1 μg) were incubated with Hesperetin (0.1–100 μM) and the substrate 4-methylumbelliferone (50 μM) in Tris-HCl buffer (pH 7.4) at 37°C for 30 minutes. Glucuronidation activity was measured using fluorescence spectroscopy (excitation wavelength: 360 nm; emission wavelength: 450 nm). IC50 values were calculated through non-linear regression analysis.
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| Cell Assay |
- Glioblastoma Cell Apoptosis Assay:
- Reference [4]: U87 cells (5×10³ cells/well) were treated with Hesperetin (0–50 μM) for 24 hours. Apoptosis was assessed using Annexin V-FITC/PI staining combined with flow cytometry. For Western blot analysis, cell lysates were probed with antibodies against phosphorylated p38 MAPK (p-p38 MAPK), Bax, Bcl-2, and caspase-3. Protein expression levels were normalized to β-actin.
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| Animal Protocol |
- Cadmium-Exposed Rat Model:
- Reference [3]: Male Wistar rats (200–250 g) were intraperitoneally injected with cadmium chloride (2.5 mg/kg) once daily for 7 days. Concurrently, Hesperetin (50 mg/kg) was administered orally once daily for 14 days. After the treatment period, brain tissues were homogenized for biochemical analysis (measurement of SOD activity and MDA levels) and immunohistochemical staining.
- Reference [1]: A Hesperetin-loaded SNEDDS formulation was prepared using soybean oil (20%), Tween 80 (60%), and ethanol (20%), with a Hesperetin dose of 100 mg/kg. Rats were given the formulation via oral gavage. Plasma samples were collected at 0, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-administration, and the concentration of Hesperetin in plasma was determined using high-performance liquid chromatography (HPLC). |
| ADME/Pharmacokinetics |
Oral bioavailability: - Reference [1]: SNEDDS formulations increased the oral bioavailability of hesperidin from 15% (suspension) to 35%. The peak plasma concentration (Cmax) of hesperidin was reached 1.5 hours after administration, with a Cmax value of 2.8 μg/mL. - Reference [2]: Hesperidin is mainly metabolized via UGT-mediated glucuronidation. The main metabolite, hesperidin-7-O-glucuronide, retains approximately 20% of the UGT inhibitory activity of the parent compound.
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| Toxicity/Toxicokinetics |
Drug interactions: - Reference [2]: Hesperidin may interact with drugs metabolized by UGT enzymes (e.g., irinotecan, morphine), potentially increasing systemic exposure to these drugs. In vitro studies have shown that hesperidin (20 μM) can enhance the cytotoxicity of irinotecan to HCT116 cells by 3-fold. - Reference [1]: No significant hepatotoxicity or nephrotoxicity was observed in rats treated with hesperidin alone at doses up to 200 mg/kg, and ALT, AST, blood urea nitrogen (BUN), and creatinine levels were normal.
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| References |
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| Additional Infomation |
Formulation optimization: - Reference [1]: The SNEDDS formulation of hesperidin significantly improved the solubility of hesperidin (from 0.03 mg/mL to 12.5 mg/mL) and enhanced its stability. The optimized formulation had an average particle size of 45 nm and a drug encapsulation rate of 98%. - Reference [3]: Hesperidin exerts its neuroprotective effect by activating the Nrf2/HO-1 signaling pathway and inhibiting NF-κB-mediated inflammation. The increased levels of Nrf2 and HO-1 proteins in the brain tissue confirmed this mechanism. - Reference [4]: Hesperidin can selectively induce apoptosis of glioblastoma cells by activating p38 MAPK and has very low toxicity to normal astrocytes, thus showing potential for the treatment of glioblastoma. 5,7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one is an ether compound belonging to the flavonoid class. It has been reported that 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one exists in citrus (Citrus reticulata), citron (Citrus medica), and other organisms with relevant data.
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| Molecular Formula |
C51H68O10
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| Molecular Weight |
841.079620000001
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| Exact Mass |
302.079
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| CAS # |
69097-99-0
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| Related CAS # |
(Rac)-Hesperetin-d3;1346605-26-2;(Rac)-Hesperetin-13C,d3;2750534-85-9
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| PubChem CID |
3593
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| Appearance |
White to yellow solid powder
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| Melting Point |
227 - 232 °C
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| LogP |
2.518
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
413
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=C(C=C(C=C1)C2CC(=O)C3=C(C=C(C=C3O2)O)O)O
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| InChi Key |
AIONOLUJZLIMTK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H14O6/c1-21-13-3-2-8(4-10(13)18)14-7-12(20)16-11(19)5-9(17)6-15(16)22-14/h2-6,14,17-19H,7H2,1H3
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| Chemical Name |
5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one
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| Synonyms |
5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one; 5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-4-one; RefChem:528235; GlyTouCan:G94164LE; G94164LE; 639-186-9; 69097-99-0; (Rac)-Hesperetin;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~413.52 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.88 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (6.88 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1889 mL | 5.9447 mL | 11.8895 mL | |
| 5 mM | 0.2378 mL | 1.1889 mL | 2.3779 mL | |
| 10 mM | 0.1189 mL | 0.5945 mL | 1.1889 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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