Natural Product (NP) Details

General Information of the NP (ID: NP5233)
Name
Wogonin
Synonyms
5,7-Dihydroxy-8-methoxyflavone; Vogonin; Norwogonin 8-methyl ether; UNII-POK93PO28W; 4H-1-Benzopyran-4-one, 5,7-dihydroxy-8-methoxy-2-phenyl-; BRN 0287152; POK93PO28W; 5,7-dihydroxy-8-methoxy-2-phenyl-4H-chromen-4-one; CHEMBL16171; FLAVONE, 5,7-DIHYDROXY-8-METHOXY-; CHEBI:10043; XLTFNNCXVBYBSX-UHFFFAOYSA-N; 5,7-dihydroxy-8-methoxy-2-phenylchromen-4-one; 5,7-Dihydroxy-8-methoxy-2-phenyl-chromen-4-one; ST077088; Q-100730; 5,7-dihydroxy-8-methoxy-2-phenyl-4H-1-benzopyran-4-one; 632-85-9
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Species Origin Arachis hypogaea ...     Click to Show/Hide
Arachis hypogaea
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Fabales
Family: Fabaceae
Genus: Arachis
Species: Arachis hypogaea
Physalis minima
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Solanales
Family: Solanaceae
Genus: Physalis
Species: Physalis minima
Anodendron affine
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Gentianales
Family: Apocynaceae
Genus: Anodendron
Species: Anodendron affine
Scutellaria amoena
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Lamiales
Family: Lamiaceae
Genus: Scutellaria
Species: Scutellaria amoena
Disease Hepatocellular carcinoma [ICD-11: 2C12] Investigative [1]
Structure
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2D MOL

3D MOL

    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C16H12O5
PubChem CID
5281703
Canonical SMILES
COC1=C(C=C(C2=C1OC(=CC2=O)C3=CC=CC=C3)O)O
InChI
1S/C16H12O5/c1-20-15-12(19)7-10(17)14-11(18)8-13(21-16(14)15)9-5-3-2-4-6-9/h2-8,17,19H,1H3
InChIKey
XLTFNNCXVBYBSX-UHFFFAOYSA-N
CAS Number
CAS 632-85-9
Herb ID
HBIN048372
ETMC ID
796
SymMap ID
SMIT00392
TCMSP ID
MOL000173
TTD Drug ID
D00MXS
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Oxaliplatin      Colorectal 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		 Up-regulation Phosphorylation JNK1  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation ULK1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Peroxynitrite formation
                    In-vitro Model BGC-823 CVCL_3360 Gastric cancer Homo sapiens
                    In-vivo Model Approximately 300 cells for the CM-Dil-labeled BGC-823 cells were injected into the yolk sac per zebrafish embryo using a microinjector.
                    Experimental
                    Result(s)		 Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells.
          Tumor necrosis factor alpha      Colorectal 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 [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Activity p105  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Neutralization TNFAlpha-induced free radical O2-
                    In-vitro Model ARAC-8C CVCL_GZ09 T acute lymphoblastic leukemia Homo sapiens
                    Experimental
                    Result(s)		 Wogonin attenuates NF-kappaB activity by shifting TNFalpha-induced free radical .O(2)(-) to a more reduced nonradical product, H(2)O(2), and thereby sensitizes TNFalpha-resistant leukemia cells to TNFalpha-induced apoptosis.
          TNF-related apoptosis inducing ligand      Lung 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 [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CFLAR  Molecule Info 
Pathway MAP
Down-regulation Expression MAGT1  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    In-vivo Model A549 non-small-cell lung cancer cells (2*106) resuspended in 0.1mL of PBS were injected subcutaneously into six weeks old athymic (nu/nu) male nude mice.
                    Experimental
                    Result(s)		 Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins.
          Sorafenib      Renal cell carcinoma     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 [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    In-vitro Model Hep 3B2.1-7 CVCL_0326 Childhood hepatocellular carcinoma Homo sapiens
BEL-7402 CVCL_5492 Human hepatocellular carcinoma Homo sapiens
Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combination of wogonin and sorafenib effectively kills human hepatocellular carcinoma cells through apoptosis potentiation and autophagy inhibition.
          5-fluorouracil      Solid tumour/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 [6]
                    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
Down-regulation Expression COX-2  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation IKKA  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
Down-regulation Expression p105  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
Down-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
                    In-vitro Model Hep-G2 CVCL_0027 Hepatocellular carcinoma Homo sapiens
SMMC-7721 CVCL_0534 Hepatocellular carcinoma Homo sapiens
                    In-vivo Model Nude mice were inoculated subcutaneously with injections of 1*107 SMMC-7721 cells/mouse at the right axilla.
                    Experimental
                    Result(s)		 Wogonin enhances 5-FU cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway.
          Doxorubicin      Solid tumour/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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression IGF1R  Molecule Info 
Pathway MAP
                    In-vitro Model BCaP-37 CVCL_0164 Breast cancer Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Wogonin increases doxorubicin sensitivity by down-regulation of IGF-1R/AKT signaling pathway in human breast cancer.
    β. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          ABT-263      Chronic lymphocytic leukaemia     Click to Show/Hide the Molecular Data of This Drug
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vitro Model ARAC-8C CVCL_GZ09 T acute lymphoblastic leukemia Homo sapiens
MOLT-4 CVCL_0013 Adult T acute lymphoblastic leukemia Homo sapiens
Jurkat CVCL_0065 T acute lymphoblastic leukemia Homo sapiens
KM-H2 CVCL_1330 Hodgkin lymphoma Homo sapiens
                    In-vivo Model Immunodeficient mice (Rag2-/-/II2rg-/-) were implanted subcutaneously in the dorsal flank region with CEM (5*107 cells).
                    Experimental
                    Result(s)		 Wogonin potentiates the lethality of ABT-263 in ABT-263-resistant cancer cells and wogonin reduces the effective dose of ABT-263 thereby possibly decreasing the risk of adverse side effects.
    γ. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Cisplatin      Bladder cancer     Click to Show/Hide the Molecular Data of This Drug
                 Reversing Drug Resistance     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression BBC3  Molecule Info 
Pathway MAP
Down-regulation Expression GABPA  Molecule Info 
Pathway MAP
Down-regulation Expression GSTP1  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Induction ROS accumulation
                    In-vitro Model AMC-HN-2 CVCL_5960 Squamous cell carcinoma Homo sapiens
AMC-HN-3 CVCL_5961 Laryngeal squamous cell carcinoma Homo sapiens
AMC-HN-4 CVCL_5962 Tongue squamous cell carcinoma Homo sapiens
AMC-HN-5 CVCL_5963 Nasal cavity squamous cell carcinoma Homo sapiens
AMC-HN-9 CVCL_5967 Mucoepidermoid carcinoma Homo sapiens
SNU-1041 CVCL_L085 Squamous cell carcinoma Homo sapiens
SNU-1066 CVCL_5005 Laryngeal squamous cell carcinoma Homo sapiens
SNU-1076 CVCL_5006 Laryngeal squamous cell carcinoma Homo sapiens
                    In-vivo Model AMC-HN4-cisR or HN9-cisR cells (5*106) were injected subcutaneously into the flank of 6-week-old athymic BALB/c male nude mice (nu/nu).
                    Experimental
                    Result(s)		 Wogonin significantly sensitized resistant HNC cells to cisplatin both in vitro and in vivo. Wogonin is a promising anticancer candidate that induces ROS accumulation and selective cytotoxicity in HNC cells and can help to overcome cisplatin-resistance in this cancer.
Target and Pathway
Target(s) Prostaglandin G/H synthase 2 (COX-2)  Molecule Info  [10]
Xanthine dehydrogenase/oxidase (XDH)  Molecule Info  [11]
BioCyc Aspirin-triggered lipoxin biosynthesis Click to Show/Hide
2 Aspirin triggered resolvin D biosynthesis
3 C20 prostanoid biosynthesis
4 Aspirin triggered resolvin E biosynthesis
5 Purine nucleotides degradation
6 Urate biosynthesis/inosine 5'-phosphate degradation
7 Guanosine nucleotides degradation
8 Adenosine nucleotides degradation
9 Retinoate biosynthesis II
KEGG Pathway Arachidonic acid metabolism Click to Show/Hide
2 Metabolic pathways
3 NF-kappa B signaling pathway
4 VEGF signaling pathway
5 TNF signaling pathway
6 Retrograde endocannabinoid signaling
7 Serotonergic synapse
8 Ovarian steroidogenesis
9 Oxytocin signaling pathway
10 Regulation of lipolysis in adipocytes
11 Leishmaniasis
12 Pathways in cancer
13 Chemical carcinogenesis
14 MicroRNAs in cancer
15 Small cell lung cancer
16 Purine metabolism
17 Caffeine metabolism
18 Drug metabolism - other enzymes
19 Peroxisome
NetPath Pathway IL1 Signaling Pathway Click to Show/Hide
2 TSH Signaling Pathway
3 IL4 Signaling Pathway
4 TGF_beta_Receptor Signaling Pathway
5 IL5 Signaling Pathway
Panther Pathway Endothelin signaling pathway Click to Show/Hide
2 Inflammation mediated by chemokine and cytokine signaling pathway
3 Toll receptor signaling pathway
4 CCKR signaling map ST
5 Adenine and hypoxanthine salvage pathway
6 Purine metabolism
Pathwhiz Pathway Arachidonic Acid Metabolism Click to Show/Hide
2 Caffeine Metabolism
3 Purine Metabolism
Pathway Interaction Database Calcineurin-regulated NFAT-dependent transcription in lymphocytes Click to Show/Hide
2 S1P1 pathway
3 C-MYB transcription factor network
4 Signaling mediated by p38-alpha and p38-beta
5 Calcium signaling in the CD4+ TCR pathway
Reactome Purine catabolism Click to Show/Hide
WikiPathways Prostaglandin Synthesis and Regulation Click to Show/Hide
2 Arachidonic acid metabolism
3 Aryl Hydrocarbon Receptor
4 Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis
5 Spinal Cord Injury
6 Integrated Pancreatic Cancer Pathway
7 Eicosanoid Synthesis
8 Selenium Micronutrient Network
9 Oxidative Stress
10 Effects of Nitric Oxide
11 Metabolism of nucleotides
References
Reference 1 Wogonin inhibits cell cycle progression by activating the glycogen synthase kinase-3 beta in hepatocellular carcinoma. Phytomedicine. 2020 Mar;68:153174.
Reference 2 Wogonin exacerbates the cytotoxic effect of oxaliplatin by inducing nitrosative stress and autophagy in human gastric cancer cells. Phytomedicine. 2018 Jan 15;39:168-175.
Reference 3 Wogonin sensitizes resistant malignant cells to TNFalpha- and TRAIL-induced apoptosis. Blood. 2006 Dec 1;108(12):3700-6.
Reference 4 Wogonin enhances antitumor activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo through ROS-mediated downregulation of cFLIPL and IAP proteins. Apoptosis. 2013 May;18(5):618-26.
Reference 5 Combination of wogonin and sorafenib effectively kills human hepatocellular carcinoma cells through apoptosis potentiation and autophagy inhibition. Oncol Lett. 2017 Jun;13(6):5028-5034.
Reference 6 Enhanced 5-fluorouracil cytotoxicity in high COX-2 expressing hepatocellular carcinoma cells by wogonin via the PI3K/Akt pathway. Biochem Cell Biol. 2013 Aug;91(4):221-9.
Reference 7 Wogonin increases doxorubicin sensitivity by down-regulation of IGF-1R/AKT signaling pathway in human breast cancer. Cell Mol Biol (Noisy-le-grand). 2015 Nov 30;61(7):123-7.
Reference 8 Targeting CDK9 by wogonin and related natural flavones potentiates the anti-cancer efficacy of the Bcl-2 family inhibitor ABT-263. Int J Cancer. 2015 Feb 1;136(3):688-98.
Reference 9 Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. Apoptosis. 2016 Nov;21(11):1265-1278.
Reference 10 Inhibitory activity of prostaglandin E2 production by the synthetic 2'-hydroxychalcone analogues: Synthesis and SAR study. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1650-3.
Reference 11 Inhibition of cow's milk xanthine oxidase by flavonoids. J Nat Prod. 1988 Mar-Apr;51(2):345-8.
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