Natural Product (NP) Details

General Information of the NP (ID: NP0031)
Name
Hesperetin
Synonyms
Hesperin; TNP00238; YSO2; Cyanidanon 4'-methyl ether 1626; Flavanone, 3',5,7-trihydroxy-4'-methoxy-(VAN); Flavanone, 3',5,7-trihydroxy-4'-methoxy-(VAN) (8CI); (-)-hesperetin; (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydro-4H-chromen-4-one; (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one; (S)-2,3-Dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4-benzopyrone; (S)-2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H-1-benzopyran-4-one; 3',5,7-Trihydroxy-4'-methoxyflavanone; 3',5,7-Trihydroxy-4-methoxyflavanone; 4H-1-Benzopyran-4-one, 2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-, (S)-(9CI); 5,7,3'-Trihydroxy-4'-methoxyflavanone
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Species Origin Citrus limon ...     Click to Show/Hide
Citrus limon
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Rutaceae
Genus: Citrus
Species: Citrus limon
Citrus sinensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Rutaceae
Genus: Citrus
Species: Citrus sinensis
Citrus unshiu
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Rutaceae
Genus: Citrus
Species: Citrus unshiu
Disease Hypertriglyceridaemia [ICD-11: 5C80] Approved [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.069
 
MDCK Permeability
 -4.81
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 -0.378
 
PPB
 97.1%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 ++
CYP1A2 substrate
 +++
CYP2C19 inhibitor
 +++
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 +++
CYP2C9 substrate
 - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 +++
CYP3A4 substrate
 - - -
CYP2B6 inhibitor
 ++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 +++
 
Excretion
CLplasma
 4.433
 
T1/2
 1.659
Toxicity
DILI
 ++
 
Rat Oral Acute Toxicity
 +
 
FDAMDD
 ++
 
Respiratory
 +++
 
Human Hepatotoxicity
 +
 
Ototoxicity
 - -
 
Drug-induced Nephrotoxicity
 +
 
Drug-induced Neurotoxicity
 +
 
Hematotoxicity
 - -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C16H14O6
PubChem CID
72281
Canonical SMILES
COC1=C(C=C(C=C1)C2CC(=O)C3=C(C=C(C=C3O2)O)O)O
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/t14-/m0/s1
InChIKey
AIONOLUJZLIMTK-AWEZNQCLSA-N
CAS Number
CAS 520-33-2
ChEBI ID
CHEBI:28230
Herb ID
HBIN029190
ETMC ID
3405
SymMap ID
SMIT04602
TCMSP ID
MOL002341
TTD Drug ID
D07MGA
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression AIFM1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression BAX  Molecule Info 
Pathway MAP
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Up-regulation Expression PTEN  Molecule Info 
Pathway MAP
Up-regulation Expression PTEN  Molecule Info 
Pathway MAP
                    In-vitro Model GES-1 CVCL_EQ22 Healthy Homo sapiens
HGC-27 CVCL_1279 Gastric carcinoma Homo sapiens
SGC-7901 CVCL_0520 Human gastric cancer Homo sapiens
MGC-803 CVCL_5334 Gastric mucinous adenocarcinoma Homo sapiens
HGC-27/DDP Gastric carcinoma Homo sapiens
                    In-vivo Model HGC-27 cells were suspended in 100 ul of PBS, and then implanted into the dorsal area, subcutaneously, of male BALB/c nude mice.
                    Experimental
                    Result(s)		 Hesperetin could inhibit the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling pathway and induce the mitochondrial pathway via upregulating PTEN expression, thereby significantly enhancing DDP's anti-tumor effect on GC.
          Platinum      Diabetes mellitus     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression UGT1A6  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
LL/2 (LLC1) CVCL_4358 Malignant tumors Mus musculus
                    In-vivo Model Xenograft tumors were established by subcutaneous injection of 1*106 LLC cells into 6-week-old male C57BL/6 mice.
                    Experimental
                    Result(s)		 Hesperetin can synergize platinum drugs by inhibiting UGT1A3 and increasing levels of reactive oxygen species (ROS).
          Doxorubicin      Solid tumour/cancer     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression HER2  Molecule Info 
Pathway MAP
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression RNASE1  Molecule Info 
Pathway MAP
                    In-vitro Model MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 The combination of Hst and Dox-induced cell cycle arrest, apoptosis, decreased HER2, Rac1, MMP9 expression, and cell migration.
          Etoposide      Testicular carcinoma     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Biological
                    Regulation		 Induction Cell cycle arrest in G2 phase
                    In-vitro Model U2OS CVCL_0042 Osteosarcoma Homo sapiens
                    Experimental
                    Result(s)		 Hesperetin combined with etoposide showed additive effects on the inhibition of cell growth.
Target and Pathway
Target(s) Diacylglycerol acyltransferase 1 (DGAT1)  Molecule Info  [6]
BioCyc Triacylglycerol biosynthesis Click to Show/Hide
KEGG Pathway Glycerolipid metabolism Click to Show/Hide
2 Retinol metabolism
3 Metabolic pathways
4 Fat digestion and absorption
Pathwhiz Pathway Retinol Metabolism Click to Show/Hide
Reactome Acyl chain remodeling of DAG and TAG Click to Show/Hide
2 Triglyceride Biosynthesis
WikiPathways Vitamin A and Carotenoid Metabolism Click to Show/Hide
2 Statin Pathway
3 Triacylglyceride Synthesis
4 Glycerophospholipid biosynthesis
5 Fatty acid, triacylglycerol, and ketone body metabolism
References
Reference 1 Drug information of Hesperetin, 2008. eduDrugs.
Reference 2 Hesperetin Promotes Cisplatin-Induced Apoptosis of Gastric Cancer In Vitro and In Vivo by Upregulating PTEN Expression. Front Pharmacol. 2020 Aug 27;11:1326.
Reference 3 Combination of hesperetin and platinum enhances anticancer effect on lung adenocarcinoma. Biomed Pharmacother. 2019 May;113:108779.
Reference 4 Cytotoxic and Antimetastatic Activity of Hesperetin and Doxorubicin Combination Toward Her2 Expressing Breast Cancer Cells. Asian Pac J Cancer Prev. 2020 May 1;21(5):1259-1267.
Reference 5 Hesperetin-etoposide combinations induce cytotoxicity in U2OS cells: Implications on therapeutic developments for osteosarcoma. DNA Repair (Amst). 2017 Feb;50:36-42.
Reference 6 In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Planta Med. 2004 Mar;70(3):258-60.
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