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Natural Product (NP) Details

General Information of the NP (ID: NP4440)
Name
Kaempferol
Synonyms
kaempferol; 520-18-3; Kaempherol; Kempferol; Trifolitin; Populnetin; Robigenin; Rhamnolutein; Pelargidenolon; Rhamnolutin; Swartziol; Indigo Yellow; Kampherol; Nimbecetin; Kampferol; Campherol; Kaemferol; 3,5,7-Trihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; 5,7,4'-Trihydroxyflavonol; Pelargidenolon 1497; 3,5,7-Trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; C.I. 75640; CCRIS 41; NSC 407289; 3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one; 4H-1-Benzopyran-4-one, 3,5,7-trihydroxy-2-(4-hydroxyphe
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Species Origin Equisetum hyemale ...     Click to Show/Hide
Equisetum hyemale
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Polypodiopsida
Order: Equisetales
Family: Equisetaceae
Genus: Equisetum
Species: Equisetum hyemale
Nelumbo nucifera
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Proteales
Family: Nelumbonaceae
Genus: Nelumbo
Species: Nelumbo nucifera
Camellia japonica
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Theaceae
Genus: Camellia
Species: Camellia japonica
Potentilla indica
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Rosales
Family: Rosaceae
Genus: Potentilla
Species: Potentilla indica
Adiantum capillus-veneris
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Polypodiopsida
Order: Polypodiales
Family: Pteridaceae
Genus: Adiantum
Species: Adiantum capillus-veneris
Camptotheca acuminata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Cornales
Family: Nyssaceae
Genus: Camptotheca
Species: Camptotheca acuminata
Cibotium barometz
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Polypodiopsida
Order: Cyatheales
Family: Cibotiaceae
Genus: Cibotium
Species: Cibotium barometz
Patrinia rupestris
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Dipsacales
Family: Caprifoliaceae
Genus: Patrinia
Species: Patrinia rupestris
Impatiens balsamina
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Balsaminaceae
Genus: Impatiens
Species: Impatiens balsamina
Asplenium prolongatum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Polypodiopsida
Order: Polypodiales
Family: Aspleniaceae
Genus: Asplenium
Species: Asplenium prolongatum
Kalanchoe pinnata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Saxifragales
Family: Crassulaceae
Genus: Kalanchoe
Species: Kalanchoe pinnata
Orostachys fimbriata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Saxifragales
Family: Crassulaceae
Genus: Orostachys
Species: Orostachys fimbriata
Litsea glutinosa
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Laurales
Family: Lauraceae
Genus: Litsea
Species: Litsea glutinosa
Melia azedarach
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Sapindales
Family: Meliaceae
Genus: Melia
Species: Melia azedarach
Equisetum ramosissimum
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Polypodiopsida
Order: Equisetales
Family: Equisetaceae
Genus: Equisetum
Species: Equisetum ramosissimum
Microcos paniculata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malvales
Family: Malvaceae
Genus: Microcos
Species: Microcos paniculata
Indigofera tinctoria
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Indigofera
Species: Indigofera tinctoria
Euscaphis japonica
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Crossosomatales
Family: Staphyleaceae
Genus: Euscaphis
Species: Euscaphis japonica
Hypericum ascyron
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Hypericaceae
Genus: Hypericum
Species: Hypericum ascyron
Lysimachia christinae
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Primulaceae
Genus: Lysimachia
Species: Lysimachia christinae
Inula japonica
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Asterales
Family: Asteraceae
Genus: Inula
Species: Inula japonica
Euphorbia lunulata
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Malpighiales
Family: Euphorbiaceae
Genus: Euphorbia
Species: Euphorbia lunulata
Lespedeza thunbergii
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Lespedeza
Species: Lespedeza thunbergii
Clematis aethusifolia
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ranunculales
Family: Ranunculaceae
Genus: Clematis
Species: Clematis aethusifolia
Lysimachia barystachys
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Ericales
Family: Primulaceae
Genus: Lysimachia
Species: Lysimachia barystachys
Disease Stomach cancer [ICD-11: 2B72] Investigative [1]
Structure
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2D MOL

3D MOL

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Formula
C15H10O6
PubChem CID
5280863
Canonical SMILES
C1=CC(=CC=C1C2=C(C(=O)C3=C(C=C(C=C3O2)O)O)O)O
InChI
1S/C15H10O6/c16-8-3-1-7(2-4-8)15-14(20)13(19)12-10(18)5-9(17)6-11(12)21-15/h1-6,16-18,20H
InChIKey
IYRMWMYZSQPJKC-UHFFFAOYSA-N
CAS Number
CAS 520-18-3
Herb ID
HBIN031753
ETMC ID
207
SymMap ID
SMIT00041
TCMSP ID
MOL000422
TTD Drug ID
D0G3TK
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    Î±. 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
                 Augmenting Drug Sensitivity     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
Down-regulation Expression MYC  Molecule Info 
Pathway MAP
                    In-vitro Model OVCAR-3 CVCL_0465 Ovarian serous adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc.
          TNF-related apoptosis inducing ligand      Lung 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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Up-regulation Expression TRAIL-R1  Molecule Info 
Pathway MAP
Up-regulation Expression TRAIL-R2  Molecule Info 
Pathway MAP
                    In-vitro Model SW480 CVCL_0546 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis.
          Sorafenib      Renal cell 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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
N1S1 Hepatocellular carcinoma Rattus norvegicus
                    Experimental
                    Result(s)
Kaempferol-mediated sensitization enhances chemotherapeutic efficacy of sorafenib against hepatocellular carcinoma.
          5-fluorouracil      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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
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
                    In-vitro Model HCT 8 CVCL_2478 Colon adenocarcinoma Homo sapiens
HCT 116 CVCL_0291 Colon carcinoma Homo sapiens
                    Experimental
                    Result(s)
Kaempferol has a synergistic effect with 5-FU by inhibiting cell proliferation and inducing apoptosis in colorectal cancer cells via suppression of TS or attenuation of p-Akt activation.
          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 [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation
Down-regulation Expression MMP-9  Molecule Info 
Pathway MAP
Down-regulation Expression mTOR  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model Huh-7 CVCL_0336 Adult hepatocellular carcinoma Homo sapiens
HuH-1 CVCL_2956 Adult hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
Hep-G2/2.2.15 CVCL_L855 Hepatoblastoma Homo sapiens
SK-HEP-1 CVCL_0525 Hepatocellular carcinoma Homo sapiens
PLC/PRF/5 CVCL_0485 Adult hepatocellular carcinoma Homo sapiens
HLE CVCL_1281 Adult hepatocellular carcinoma Homo sapiens
HLF CVCL_2947 Adult hepatocellular carcinoma Homo sapiens
Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)
Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer.
Target and Pathway
Target(s) Aldose reductase (AKR1B1)  Molecule Info  [7]
Androgen receptor (AR)  Molecule Info  [8]
Arachidonate 15-lipoxygenase (15-LOX)  Molecule Info  [9]
Cytochrome P450 1B1 (CYP1B1)  Molecule Info  [10]
Estradiol 17 beta-dehydrogenase 1 (17-beta-HSD1)  Molecule Info  [11]
Influenza Neuraminidase (Influ NA)  Molecule Info  [12]
Lactoylglutathione lyase (GLO1)  Molecule Info  [13]
Plasmodium 3-oxoacyl-acyl-carrier reductase (Malaria fabG)  Molecule Info  [14]
BioCyc Methylglyoxal degradation III Click to Show/Hide
2 Acetone degradation I (to methylglyoxal)
3 Superpathway of tryptophan utilization
4 Superpathway of melatonin degradation
5 Melatonin degradation I
6 Superpathway of steroid hormone biosynthesis
7 Estradiol biosynthesis I
8 Methylglyoxal degradation I
9 Resolvin D biosynthesis
10 Lipoxin biosynthesis
KEGG Pathway Oocyte meiosis Click to Show/Hide
2 Pathways in cancer
3 Prostate cancer
4 Pentose and glucuronate interconversions
5 Fructose and mannose metabolism
6 Galactose metabolism
7 Glycerolipid metabolism
8 Metabolic pathways
9 Steroid hormone biosynthesis
10 Tryptophan metabolism
11 Metabolism of xenobiotics by cytochrome P450
12 Ovarian steroidogenesis
13 Chemical carcinogenesis
14 MicroRNAs in cancer
15 Pyruvate metabolism
16 Arachidonic acid metabolism
17 Linoleic acid metabolism
18 Serotonergic synapse
19 Other glycan degradation
NetPath Pathway EGFR1 Signaling Pathway Click to Show/Hide
2 AndrogenReceptor Signaling Pathway
3 FSH Signaling Pathway
4 IL1 Signaling Pathway
5 TGF_beta_Receptor Signaling Pathway
6 TSH Signaling Pathway
7 IL4 Signaling Pathway
8 TCR Signaling Pathway
Panther Pathway Androgen/estrogene/progesterone biosynthesis Click to Show/Hide
2 Inflammation mediated by chemokine and cytokine signaling pathway
Pathwhiz Pathway Fructose and Mannose Degradation Click to Show/Hide
2 Pyruvate Metabolism
3 Pterine Biosynthesis
4 Glycerolipid Metabolism
5 Galactose Metabolism
6 Androgen and Estrogen Metabolism
7 Pyruvaldehyde Degradation
8 Arachidonic Acid Metabolism
Pathway Interaction Database Regulation of nuclear SMAD2/3 signaling Click to Show/Hide
2 Coregulation of Androgen receptor activity
3 Regulation of Androgen receptor activity
4 Nongenotropic Androgen signaling
5 Regulation of nuclear beta catenin signaling and target gene transcription
6 FOXA1 transcription factor network
7 Notch-mediated HES/HEY network
8 IL4-mediated signaling events
Reactome Nuclear Receptor transcription pathway Click to Show/Hide
2 Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
3 Endogenous sterols
4 The canonical retinoid cycle in rods (twilight vision)
5 Pyruvate metabolism
WikiPathways SIDS Susceptibility Pathways Click to Show/Hide
2 Integrated Pancreatic Cancer Pathway
3 Prostate Cancer
4 Integrated Breast Cancer Pathway
5 Nuclear Receptors
6 Androgen receptor signaling pathway
7 Metapathway biotransformation
8 Polyol Pathway
9 Metabolism of steroid hormones and vitamin D
10 Estrogen metabolism
11 Benzo(a)pyrene metabolism
12 Tamoxifen metabolism
13 Tryptophan metabolism
14 Oxidation by Cytochrome P450
15 Nuclear Receptors Meta-Pathway
16 Estrogen Receptor Pathway
17 Sulindac Metabolic Pathway
18 Arylhydrocarbon receptor (AhR) signaling pathway
19 miR-targeted genes in muscle cell - TarBase
20 miR-targeted genes in lymphocytes - TarBase
21 miR-targeted genes in epithelium - TarBase
22 miR-targeted genes in adipocytes - TarBase
23 Phase 1 - Functionalization of compounds
24 Steroid Biosynthesis
25 Arachidonic acid metabolism
26 Eicosanoid Synthesis
References
Reference 1 Kaempferol induces autophagic cell death via IRE1-JNK-CHOP pathway and inhibition of G9a in gastric cancer cells. Cell Death Dis. 2018 Aug 29;9(9):875.
Reference 2 Kaempferol enhances cisplatin's effect on ovarian cancer cells through promoting apoptosis caused by down regulation of cMyc. Cancer Cell Int. 2010 May 11;10:16.
Reference 3 Kaempferol sensitizes colon cancer cells to TRAIL-induced apoptosis. Biochem Biophys Res Commun. 2008 Oct 10;375(1):129-33.
Reference 4 Kaempferol-Mediated Sensitization Enhances Chemotherapeutic Efficacy of Sorafenib Against Hepatocellular Carcinoma: An In Silico and In Vitro Approach. Adv Pharm Bull. 2020 Jul;10(3):472-476.
Reference 5 Synergistic effect of kaempferol and 5?fluorouracil on the growth of colorectal cancer cells by regulating the PI3K/Akt signaling pathway. Mol Med Rep. 2019 Jul;20(1):728-734.
Reference 6 Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncol Rep. 2021 Apr;45(4):32.
Reference 7 Erigeroflavanone, a flavanone derivative from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity. J Nat Prod. 2008 Apr;71(4):713-5.
Reference 8 Effect of flavonoids on androgen and glucocorticoid receptors based on in vitro reporter gene assay. Bioorg Med Chem Lett. 2009 Aug 15;19(16):4706-10.
Reference 9 Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti. J Nat Prod. 2007 May;70(5):859-62.
Reference 10 Selective inhibition of methoxyflavonoids on human CYP1B1 activity. Bioorg Med Chem. 2010 Sep 1;18(17):6310-5.
Reference 11 Discovery of nonsteroidal 17beta-hydroxysteroid dehydrogenase 1 inhibitors by pharmacophore-based screening of virtual compound libraries. J Med Chem. 2008 Jul 24;51(14):4188-99.
Reference 12 Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea roots and their in vitro anti-influenza viral activities. Bioorg Med Chem. 2009 Oct 1;17(19):6816-23.
Reference 13 Structure-activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorg Med Chem. 2008 Apr 1;16(7):3969-75.
Reference 14 Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids. J Med Chem. 2006 Jun 1;49(11):3345-53.
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Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China