Natural Product (NP) Details

General Information of the NP (ID: NP3718)
Name
Honokiol
Synonyms
5,3'-Diallyl-2,4'-dihydroxybiphenyl; NSC 293100; Honokiol,(S); UNII-11513CCO0N; 3,5'-Diallyl-4,2'-dihydroxybiphenyl; 3',5-Diallylbiphenyl-2,4'-diol; CPD000387107; CHEMBL16901; CHEBI:5759; 4-allyl-2-(3-allyl-4-hydroxy-phenyl)phenol; 3',5-diallyl-[1,1'-biphenyl]-2,4'-diol; 11513CCO0N; 3',5-diallyl-2,4'-biphenyldiol; AK-25837; 5,3& -Diallyl-2,4& Q-100425; [1,1'-Biphenyl]-2,4'-diol, 3',5-di-2-propenyl-; SMR000387107; 3',5-di(prop-2-en-1-yl)biphenyl-2,4'-diol; houpa; 35354-74-6
    Click to Show/Hide
Species Origin Magnolia officinalis ...     Click to Show/Hide
Magnolia officinalis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Magnoliales
Family: Magnoliaceae
Genus: Magnolia
Species: Magnolia officinalis
Spiranthes bightensis
Kingdom: Viridiplantae
Phylum: Streptophyta
Class: Magnoliopsida
Order: Asparagales
Family: Orchidaceae
Genus: Spiranthes
Species: Spiranthes bightensis
Disease Pancreatic cancer [ICD-11: 2C10] Investigative [1]
Structure
Click to Download Mol
2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -4.611
 
MDCK Permeability
 -4.672
 
PAMPA
 - - -
 
HIA
 - - -
 
Distribution
VDss
 0.328
 
PPB
 93.4%
 
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
 13.722
 
T1/2
 1.054
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.
    Click to Show/Hide
    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C18H18O2
PubChem CID
72303
Canonical SMILES
C=CCC1=CC(=C(C=C1)O)C2=CC(=C(C=C2)O)CC=C
InChI
1S/C18H18O2/c1-3-5-13-7-9-18(20)16(11-13)14-8-10-17(19)15(12-14)6-4-2/h3-4,7-12,19-20H,1-2,5-6H2
InChIKey
FVYXIJYOAGAUQK-UHFFFAOYSA-N
CAS Number
CAS 35354-74-6
Herb ID
HBIN029531
ETMC ID
2851
SymMap ID
SMIT00240
TCMSP ID
MOL005955
TTD Drug ID
D04DQJ
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Temozolomide      Brain 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 CASP3  Molecule Info 
Pathway MAP
                    In-vitro Model U-87MG ATCC CVCL_0022 Glioblastoma Homo sapiens
GL261 CVCL_Y003 Mouse glioblastoma Mus musculus
                    Experimental
                    Result(s)		 Honokiol enhanced temozolomide-induced autophagy and apoptosis in drug-sensitive and -tolerant glioma cells.
          Oxaliplatin      Colorectal 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		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK1  Molecule Info 
Pathway MAP
Down-regulation Expression ERK2  Molecule Info 
Pathway MAP
Down-regulation Expression RELA  Molecule Info 
Pathway MAP
                    In-vitro Model HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells.
          Bleomycin      Hodgkin lymphoma     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 Activity POLB  Molecule Info 
Pathway MAP
Down-regulation Activity POLL  Molecule Info 
Pathway MAP
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
PANC-1 CVCL_0480 Pancreatic ductal adenocarcinoma Homo sapiens
UACC-903 CVCL_4052 Cutaneous melanoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol inhibits DNA polymerases Beta and Lambda and increases Bleomycin sensitivity of human cancer cells.
          Chloroquine      Malaria     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		 Up-regulation Expression MAP1LC3A  Molecule Info 
Pathway MAP
Up-regulation Expression SQSTM1  Molecule Info 
Pathway MAP
                    In-vitro Model NCI-H460 CVCL_0459 Lung large cell carcinoma Homo sapiens
A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells.
          Rapamycin      Multiple myeloma     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 PD-L1  Molecule Info 
Pathway MAP
                    In-vitro Model 786-O CVCL_1051 Renal cell carcinoma Homo sapiens
ACHN CVCL_1067 Papillary renal cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol can effectively overcome the limitation of Rapamycin treatment alone, and the combination treatment can markedly restrict the growth of RCC, with particular importance to post-transplantation renal cancer.
          Rosiglitazone      Prostate 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 [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression CCND1  Molecule Info 
Pathway MAP
Down-regulation Expression CCNE1  Molecule Info 
Pathway MAP
Up-regulation Expression CDKN1A  Molecule Info 
Pathway MAP
Down-regulation Expression RB1  Molecule Info 
Pathway MAP
                    In-vitro Model Mahlavu CVCL_0405 Hepatocellular carcinoma Homo sapiens
SK-HEP-1 CVCL_0525 Hepatocellular carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol combined with rosiglitazone showed more effective growth inhibition in hepatoma cells mediated through the regulation of G0/G1 phase-related proteins p21, cyclin D1, cyclin E1, and Rb and cell cycle progression.
          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 [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Down-regulation Phosphorylation EGFR  Molecule Info 
Pathway MAP
                    Biological
                    Regulation		 Up-regulation Cytochrome c release
                    In-vitro Model HSC-3 CVCL_1288 Tongue squamous cell carcinoma Homo sapiens
HSC-4 CVCL_1289 Tongue squamous cell carcinoma Homo sapiens
                    In-vivo Model A total of 2*106 HSC-3 cells were suspended in 100 uL serum-free DMEM and injected subcutaneously into the right flank of BALB/c nude mice to establish OSCC xenograft models.
                    Experimental
                    Result(s)		 HNK and 5-FU exert a synergistic therapeutic effect on OSCC by inducing apoptosis.
          Gemcitabine      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 [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Phosphorylation NFKBIA  Molecule Info 
Pathway MAP
                    Experimental
                    Result(s)		 Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells.
          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 [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model SK-OV-3 CVCL_0532 Ovarian serous cystadenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Combining liposomal honokiol with cisplatin enhances therapeutic effectiveness in ovarian carcinoma.
          Imatinib      Mantle cell lymphoma     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 [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model NB4 CVCL_0005 Acute promyelocytic leukemia Homo sapiens
K-562 CVCL_0004 Chronic myelogenous leukemia Homo sapiens
                    Experimental
                    Result(s)		 Honokiol induces paraptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells.
          X-ray irradiation      Scaphoid Fracture     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 [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model A-549 CVCL_0023 Lung adenocarcinoma Homo sapiens
NCI-H1299 CVCL_0060 Lung large cell carcinoma Homo sapiens
                    Experimental
                    Result(s)		 Honokiol demonstrated low cytotoxicity to NSCLC cells and a pronounced radiosensitizing effect on NSCLC cells exposed to carbon ions than X-rays.
          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 [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model 4T1 CVCL_0125 Malignant neoplasms Mus musculus
BCaP-37 CVCL_0164 Breast cancer Homo sapiens
MCF-7 CVCL_0031 Invasive breast carcinoma Homo sapiens
                    In-vivo Model Mouse 4T1 breast cancer cells (1.0*105) were suspended in 0.1 mL of normal saline (NS) and injected subcutaneously in theright axillary fossa of BALB/c mice.
                    Experimental
                    Result(s)		 Honokiol inhibited the proliferation of 4T1 cells via apoptosis and significantly enhanced the apoptosis of 4T1 cells induced by adriamycin.
    β. A List of Drug(s) Whose Adverse Effect can be Decreased by This NP
          Celecoxib      Rheumatoid arthritis     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 [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression FOXM1  Molecule Info 
Pathway MAP
Down-regulation Expression FOXP3  Molecule Info 
Pathway MAP
Down-regulation Expression ITGAM  Molecule Info 
Pathway MAP
Down-regulation Expression MKI67  Molecule Info 
Pathway MAP
Down-regulation Expression NNT  Molecule Info 
Pathway MAP
Down-regulation Expression PECAM1  Molecule Info 
Pathway MAP
Down-regulation Expression VEGFA  Molecule Info 
Pathway MAP
                    In-vitro Model 4T1 CVCL_0125 Malignant neoplasms Mus musculus
                    Experimental
                    Result(s)		 The combined treatment with PV-CXB and PV-HNK showed synergistic effect both in vitro and in vivo.
    γ. A List of Drug(s) Whose Resistance can be Reversed by This NP
          Osimertinib      Lung 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 [15]
                    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 PC-9 CVCL_B260 Lung adenocarcinoma Homo sapiens
HCC827 CVCL_2063 Lung adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)		 Overcoming acquired resistance of EGFR-mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib, with the natural product honokiol.
Target and Pathway
Target(s) Arachidonate 5-lipoxygenase (5-LOX)  Molecule Info  [16]
Prostaglandin-endoperoxide synthas (COX)  Molecule Info  [16]
BioCyc Aspirin-triggered lipoxin biosynthesis Click to Show/Hide
2 Resolvin D biosynthesis
3 Leukotriene biosynthesis
4 Lipoxin biosynthesis
5 Aspirin triggered resolvin D biosynthesis
6 Aspirin triggered resolvin E biosynthesis
KEGG Pathway Arachidonic acid metabolism Click to Show/Hide
2 Metabolic pathways
3 Serotonergic synapse
4 Ovarian steroidogenesis
5 Toxoplasmosis
NetPath Pathway IL4 Signaling Pathway Click to Show/Hide
Pathwhiz Pathway Arachidonic Acid Metabolism Click to Show/Hide
WikiPathways Vitamin D Receptor Pathway Click to Show/Hide
2 Arachidonic acid metabolism
3 Eicosanoid Synthesis
4 Selenium Micronutrient Network
References
Reference 1 Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis. Cancer Manag Res. 2020 Jul 1;12:5243-5254.
Reference 2 Improved effects of honokiol on temozolomide-induced autophagy and apoptosis of drug-sensitive and -tolerant glioma cells. BMC Cancer. 2018 Apr 3;18(1):379.
Reference 3 Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells. Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):773-9.
Reference 4 Honokiol Inhibits DNA Polymerases Beta and Lambda and Increases Bleomycin Sensitivity of Human Cancer Cells. Chem Res Toxicol. 2017 Feb 20;30(2):715-725.
Reference 5 Honokiol exhibits enhanced antitumor effects with chloroquine by inducing cell death and inhibiting autophagy in human non-small cell lung cancer cells. Oncol Rep. 2015 Sep;34(3):1289-300.
Reference 6 A Novel Combination Treatment with Honokiol and Rapamycin Effectively Restricts c-Met-Induced Growth of Renal Cancer Cells, and also Inhibits the Expression of Tumor Cell PD-L1 Involved in Immune Escape. Cancers (Basel). 2020 Jul 3;12(7):1782.
Reference 7 Combined effect of honokiol and rosiglitazone on cell growth inhibition through enhanced G0/G1 phase arrest in hepatoma cells. J Chin Med Assoc. 2016 Aug;79(8):415-21.
Reference 8 Synergistic effect of honokiol and 5-fluorouracil on apoptosis of oral squamous cell carcinoma cells. J Oral Pathol Med. 2017 Mar;46(3):201-207.
Reference 9 Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PLoS One. 2011;6(6):e21573.
Reference 10 Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma. Int J Gynecol Cancer. Jul-Aug 2008;18(4):652-9.
Reference 11 Honokiol induces paraptosis and apoptosis and exhibits schedule-dependent synergy in combination with imatinib in human leukemia cells. Toxicol Mech Methods. 2010 Jun;20(5):234-41.
Reference 12 Radiosensitization of NSCLC cells to X-rays and carbon ions by the CHK1/CHK2 inhibitor AZD7762, Honokiol and Tunicamycin. Radiat Environ Biophys. 2020 Nov;59(4):723-732.
Reference 13 Synergistic antitumor effects of liposomal honokiol combined with adriamycin in breast cancer models. Phytother Res. 2008 Aug;22(8):1125-32.
Reference 14 Tuning mPEG-PLA/vitamin E-TPGS-based mixed micelles for combined celecoxib/honokiol therapy for breast cancer. Eur J Pharm Sci. 2020 Apr 15;146:105277.
Reference 15 Overcoming acquired resistance of EGFR-mutant NSCLC cells to the third generation EGFR inhibitor, osimertinib, with the natural product honokiol. Mol Oncol. 2020 Apr;14(4):882-895.
Reference 16 Design and synthesis of ten biphenyl-neolignan derivatives and their in vitro inhibitory potency against cyclooxygenase-1/2 activity and 5-lipoxyge... Bioorg Med Chem. 2009 Jul 1;17(13):4459-65.
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link      
 Download Picture         KEGG Link