Natural Product (NP) Details

General Information of the NP (ID: NP0478)
Name
Xanthohumol
Synonyms
Xanthohumol; 6754-58-1; 1-(2,4-Dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; 569-83-5; UNII-T4467YT1NT; T4467YT1NT; CHEBI:66331; 2',4,4'-trihydroxy-6'-methoxy-3'-prenylchalcone; 1-(2,4-Dihydroxy-6-methoxy-3-(3-methyl-2-butenyl)phenyl)-3-(4-hydroxyphenyl)-2-propen-1-one; (2E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one; (E)-1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)prop-2-en-1-one; (E)-1-(2,4-Dihydroxy-6-methoxy-3-(3-methylbut-2-en-1-yl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; 1-[2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one; (E)-1-(2,4-dihydroxy-6-methoxy-3-(3-methylbut-2-enyl)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one; XANTHOHUMO; 2',4,4'-Trihydroxy-3'-prenyl-6'-methoxychalcone; SCHEMBL143683; CHEMBL253896; MEGxp0_000104; ACon1_001634; CHEBI:94745; DTXSID00893171; Xanthohumol(Random Configuration); HMS3886H19; BCP18498; ZINC5158937; 0397AC; BDBM50384998; LMPK12120294; MFCD00210576; s7889; AKOS016010098; CCG-268086; DB15359; MCULE-7307777782; (E)-1-[2,4-Dihydroxy-6-methoxy-3-(3-methyl-2-butenyl)phenyl]-3-(4-hydroxyphenyl)propenone; SMP2_000278; NCGC00180304-01; AC-31276; BS-17392; W2672; C16417; Q408088; BRD-K77390737-001-01-6; Q27166535; Xanthohumol, primary pharmaceutical reference standard; Xanthohumol from hop (Humulus lupulus), >=96% (HPLC); (2E)-1-[2,4-Dihydroxy-6-methoxy-3-(3-methyl-2-buten-1-yl)phenyl]-3-(4-hydroxyphenyl)-2-propen-1-one; 1-[2,4-Dihydroxy-6-methoxy-3-(3-methyl-but-2-enyl)-phenyl]-3-(4-hydroxy-phenyl)-propenone; 2-Propen-1-one, 1-(2,4-hydroxy-6-methoxy-3-(3-methyl-2-butenyl)phenyl)-3-(4-hydroxyphenyl)-, (E)-
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Species Origin Humulus lupulus ...     Click to Show/Hide
Humulus lupulus
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Rosales
Family: Cannabaceae
Genus: Humulus
Species: Humulus lupulus
Disease Acute lung injury [ICD-11: NB32] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -5.056
 
MDCK Permeability
 -4.821
 
PAMPA
 - -
 
HIA
 - - -
 
Distribution
VDss
 0.23
 
PPB
 95.6%
 
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
 7.297
 
T1/2
 0.865
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
C21H22O5
PubChem CID
639665
Canonical SMILES
CC(=CCC1=C(C(=C(C=C1O)OC)C(=O)C=CC2=CC=C(C=C2)O)O)C
InChI
1S/C21H22O5/c1-13(2)4-10-16-18(24)12-19(26-3)20(21(16)25)17(23)11-7-14-5-8-15(22)9-6-14/h4-9,11-12,22,24-25H,10H2,1-3H3/b11-7+
InChIKey
ORXQGKIUCDPEAJ-YRNVUSSQSA-N
CAS Number
CAS 6754-58-1
ChEBI ID
CHEBI:66331
Herb ID
HBIN048442
SymMap ID
SMIT00652
TCMSP ID
MOL006653
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Praziquantel      Flatworm infection     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		 Down-regulation Expression CD44  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation p38 beta  Molecule Info 
Pathway MAP
Down-regulation Expression TFRC  Molecule Info 
Pathway MAP
                    In-vivo Model Six- to eight-week-old male Syrian golden hamsters were used in this study.
                    Experimental
                    Result(s)		 XN administered in combination with PZ could efficiently prevent CCA development and hence provide potential chemopreventive benefits in Ov-induced cholangiocarcinogenesis.
Target and Pathway
Target(s) Acetyl-CoA carboxylase kinase 1 (PRKAA1)  Molecule Info  [3]
Acetyl-CoA carboxylase kinase 2 (PRKAA2)  Molecule Info  [3]
Apoptosis regulator BAX (BAX)  Molecule Info 
Apoptosis regulator Bcl-2 (BCL-2)  Molecule Info 
C-X-C motif chemokine 1 (CXCL1)  Molecule Info  [4]
Glycogen synthase kinase-3 beta (GSK-3B)  Molecule Info  [1]
Intercellular adhesion ICAM-1 (ICAM1)  Molecule Info  [5]
Monocyte secretory JE (CCL2)  Molecule Info  [4]
NAD-dependent deacetylase sirtuin-1 (SIRT1)  Molecule Info  [6]
Nuclear factor erythroid 2-related factor 2 (Nrf2)  Molecule Info  [3]
[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial  Molecule Info  [4]
KEGG Pathway ErbB signaling pathway Click to Show/Hide
2 Chemokine signaling pathway
3 Cell cycle
4 PI3K-Akt signaling pathway
5 Wnt signaling pathway
6 Hedgehog signaling pathway
7 Axon guidance
8 Hippo signaling pathway
9 Focal adhesion
10 Signaling pathways regulating pluripotency of stem cells
11 T cell receptor signaling pathway
12 B cell receptor signaling pathway
13 Neurotrophin signaling pathway
14 Dopaminergic synapse
15 Insulin signaling pathway
16 Melanogenesis
17 Prolactin signaling pathway
18 Thyroid hormone signaling pathway
19 Non-alcoholic fatty liver disease (NAFLD)
20 Alzheimer's disease
21 Hepatitis C
22 Measles
23 Influenza A
24 HTLV-I infection
25 Epstein-Barr virus infection
26 Pathways in cancer
27 Colorectal cancer
28 Endometrial cancer
29 Prostate cancer
30 Basal cell carcinoma
31 Cytokine-cytokine receptor interaction
32 NOD-like receptor signaling pathway
33 TNF signaling pathway
34 Chagas disease (American trypanosomiasis)
35 Malaria
36 Herpes simplex infection
37 Rheumatoid arthritis
38 NF-kappa B signaling pathway
39 Cell adhesion molecules (CAMs)
40 Natural killer cell mediated cytotoxicity
41 Leukocyte transendothelial migration
42 African trypanosomiasis
43 Staphylococcus aureus infection
44 Viral myocarditis
45 Protein processing in endoplasmic reticulum
46 FoxO signaling pathway
47 AMPK signaling pathway
48 Glucagon signaling pathway
49 Amphetamine addiction
50 MicroRNAs in cancer
NetPath Pathway IL9 Signaling Pathway Click to Show/Hide
2 IL5 Signaling Pathway
3 IL1 Signaling Pathway
4 TSH Signaling Pathway
5 TWEAK Signaling Pathway
6 IL4 Signaling Pathway
7 TNFalpha Signaling Pathway
8 TSLP Signaling Pathway
9 Leptin Signaling Pathway
10 RANKL Signaling Pathway
11 IL6 Signaling Pathway
12 IL2 Signaling Pathway
13 ID Signaling Pathway
Panther Pathway Alzheimer disease-presenilin pathway Click to Show/Hide
2 Angiogenesis
3 Cadherin signaling pathway
4 Hedgehog signaling pathway
5 Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway
6 Insulin/IGF pathway-protein kinase B signaling cascade
7 Interleukin signaling pathway
8 PDGF signaling pathway
9 PI3 kinase pathway
10 Wnt signaling pathway
11 Ras Pathway
12 CCKR signaling map ST
13 Inflammation mediated by chemokine and cytokine signaling pathway
14 p53 pathway
Pathway Interaction Database LPA receptor mediated events Click to Show/Hide
2 Degradation of beta catenin
3 Reelin signaling pathway
4 Presenilin action in Notch and Wnt signaling
5 Integrin-linked kinase signaling
6 CDC42 signaling events
7 LKB1 signaling events
8 Canonical Wnt signaling pathway
9 Role of Calcineurin-dependent NFAT signaling in lymphocytes
10 Glucocorticoid receptor regulatory network
11 C-MYC pathway
12 Regulation of Androgen receptor activity
13 BMP receptor signaling
14 Hedgehog signaling events mediated by Gli proteins
15 Signaling events mediated by Stem cell factor receptor (c-Kit)
16 Validated transcriptional targets of deltaNp63 isoforms
17 Aurora A signaling
18 Insulin-mediated glucose transport
19 Class I PI3K signaling events mediated by Akt
20 p53 pathway
21 Trk receptor signaling mediated by PI3K and PLC-gamma
22 GMCSF-mediated signaling events
23 Validated transcriptional targets of AP1 family members Fra1 and Fra2
24 AP-1 transcription factor network
25 IL23-mediated signaling events
26 Thromboxane A2 receptor signaling
27 amb2 Integrin signaling
28 Beta2 integrin cell surface interactions
29 p73 transcription factor network
30 Signaling events mediated by HDAC Class III
31 E2F transcription factor network
32 HIF-2-alpha transcription factor network
33 Signaling events mediated by HDAC Class I
34 FoxO family signaling
35 Regulation of retinoblastoma protein
Reactome Degradation of beta-catenin by the destruction complex Click to Show/Hide
2 AKT phosphorylates targets in the cytosol
3 Regulation of HSF1-mediated heat shock response
4 CRMPs in Sema3A signaling
5 Disassembly of the destruction complex and recruitment of AXIN to the membrane
6 S33 mutants of beta-catenin aren't phosphorylated
7 S37 mutants of beta-catenin aren't phosphorylated
8 S45 mutants of beta-catenin aren't phosphorylated
9 T41 mutants of beta-catenin aren't phosphorylated
10 Degradation of GLI2 by the proteasome
11 Constitutive Signaling by AKT1 E17K in Cancer
12 Chemokine receptors bind chemokines
13 ATF4 activates genes
14 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
15 Integrin cell surface interactions
16 Interferon gamma signaling
17 RORA activates gene expression
18 Circadian Clock
WikiPathways DNA Damage Response (only ATM dependent) Click to Show/Hide
2 Senescence and Autophagy in Cancer
3 Notch Signaling Pathway
4 Glycogen Metabolism
5 Insulin Signaling
6 Wnt Signaling Pathway
7 Wnt Signaling Pathway and Pluripotency
8 IL-6 signaling pathway
9 Wnt Signaling Pathway Netpath
10 Copper homeostasis
11 Focal Adhesion
12 Hair Follicle Development: Induction (Part 1 of 3)
13 Cardiac Hypertrophic Response
14 Degradation of beta-catenin by the destruction complex
15 T-Cell Receptor and Co-stimulatory Signaling
16 Cardiac Progenitor Differentiation
17 BDNF signaling pathway
18 Corticotropin-releasing hormone
19 B Cell Receptor Signaling Pathway
20 IL17 signaling pathway
21 Neural Crest Differentiation
22 Alzheimers Disease
23 IL-7 Signaling Pathway
24 Regulation of Microtubule Cytoskeleton
25 TWEAK Signaling Pathway
26 Leptin signaling pathway
27 Semaphorin interactions
28 Cell Cycle
29 MicroRNAs in cardiomyocyte hypertrophy
30 Androgen receptor signaling pathway
31 IL-5 Signaling Pathway
32 IL1 and megakaryotyces in obesity
33 Activation of Genes by ATF4
34 Spinal Cord Injury
35 Oncostatin M Signaling Pathway
36 TNF alpha Signaling Pathway
37 IL-1 signaling pathway
38 GPCR ligand binding
39 Folate Metabolism
40 Vitamin B12 Metabolism
41 Selenium Micronutrient Network
42 Type II interferon signaling (IFNG)
43 Human Complement System
44 Interleukin-11 Signaling Pathway
45 RANKL/RANK Signaling Pathway
46 Integrin cell surface interactions
47 Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
48 Oxidative Stress
49 Transcriptional activation by NRF2
50 NRF2 pathway
51 Nuclear Receptors Meta-Pathway
52 Aryl Hydrocarbon Receptor Pathway
53 Mesodermal Commitment Pathway
54 Aryl Hydrocarbon Receptor
55 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
56 Arylhydrocarbon receptor (AhR) signaling pathway
57 Integrated Pancreatic Cancer Pathway
58 SREBF and miR33 in cholesterol and lipid homeostasis
59 Integrated Breast Cancer Pathway
60 SREBP signalling
References
Reference 1 Xanthohumol ameliorates lipopolysaccharide (LPS)-induced acute lung injury via induction of AMPK/GSK3Beta-Nrf2 signal axis. Redox Biol. 2017 Aug;12:311-324.
Reference 2 Antifibrotic effect of xanthohumol in combination with praziquantel is associated with altered redox status and reduced iron accumulation during liver fluke-associated cholangiocarcinogenesis. PeerJ. 2018 Jan 22;6:e4281.
Reference 3 Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response. Free Radic Biol Med. 2015 Nov;88(Pt B):417-426.
Reference 4 Therapeutic Application of Micellar Solubilized Xanthohumol in a Western-Type Diet-Induced Mouse Model of Obesity, Diabetes and Non-Alcoholic Fatty Liver Disease. Cells. 2019 Apr 17;8(4):359.
Reference 5 Xanthohumol attenuates tumour cell-mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis. Arch Toxicol. 2013 Jul;87(7):1301-12.
Reference 6 Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release. Free Radic Biol Med. 2017 Jul;108:247-257.
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