Honokiol / antiOx Cancer Research Results

HNK, Honokiol: Click to Expand ⟱
Features:
Honokiol is a Lignan isolated from bark, seed cones and leaves of trees of Magnolia species. Honokiol was traditionally used for anxiety and stroke treatment, as well as the alleviation of flu symptoms.
-considered to have antioxidant properties
-low oral bioavailability and difficulty in intravenous administration
-the development of various formulations of honokiol, including microemulsion, liposomes, nanoparticles and micelle copolymers have successfully solved the problem of low water solubility.

Pathways:
-Inhibit NF-κB activation
-Downregulate STAT3 signalin
-Inhibiting the PI3K/Akt pathway,
-Inhibition of mTOR
-Influences various MAPK cascades—including ERK, JNK, and p38
-Inhibition of EGFR
-Inhibiting Notch pathway (CSCs)
-GPx4 inhibit
-Can induce ER stress in cancer cells, which contributes to the activation of unfolded protein response (UPR) pathways
-Disrupt the mitochondrial membrane potential in cancer cells.
-Reported to increase ROS production in cancer cells
-Can exhibit antioxidant properties in normal cells. - has some inhibitor activity but Not classified as HDAC inhibitor as weaker and may work more indirectly.
- is well-known in the research community for its role in activating SIRT3

-Note half-life 40–60 minutes
BioAv
Pathways:
- induce ROS production in cancer cells, and typically lowers ROS in normal cells
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ Prx
- Raises antiOx↑">AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, ROCK1↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓
- reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓,
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓,
- inhibits glycolysis and ATP depletion : HIF-1α↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓,
- inhibits Cancer Stem Cells : CSC↓, CD133↓, β-catenin↓, sox2↓, nestin↓, OCT4↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol).
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Rank Pathway / Axis Cancer Cells Normal Cells Label Primary Interpretation Notes
1 Mitochondrial integrity / intrinsic apoptosis ↓ ΔΨm; ↑ cytochrome-c release; ↑ caspases ↔ largely preserved Driver Mitochondria-directed cytotoxicity Honokiol directly accumulates in mitochondria and initiates intrinsic apoptosis in cancer cells
2 Reactive oxygen species (ROS) ↑ ROS (secondary, stress-amplifying) ↔ buffered Secondary Mitochondrial stress amplification ROS elevation follows mitochondrial perturbation rather than acting as the initiating trigger
3 STAT3 signaling ↓ STAT3 activation ↔ minimal Driver Loss of survival and stemness signaling STAT3 suppression contributes to apoptosis, CSC targeting, and reduced proliferation
4 PI3K → AKT → mTOR axis ↓ AKT / ↓ mTOR ↔ adaptive suppression Secondary Growth and anabolic inhibition AKT/mTOR inhibition reinforces mitochondrial and apoptotic stress
5 NF-κB signaling ↓ NF-κB activation ↓ inflammatory NF-κB tone Secondary Suppression of survival transcription NF-κB inhibition contributes to chemosensitization and anti-inflammatory effects
6 Cell cycle regulation ↑ G0/G1 or G2/M arrest ↔ spared Phenotypic Cytostatic growth control Cell-cycle arrest reflects upstream signaling disruption
7 Autophagy ↑ autophagy (context-dependent) ↑ adaptive autophagy Adaptive Stress response vs death cooperation Autophagy may precede apoptosis or act as a transient survival response


antiOx, anti-oxidant activities: Click to Expand ⟱
Source:
Type:
Various antioxidants such as Nrf2, SODs, catalase, GPxs, PRDXs, and GSTs are altered in different cancers and have been linked to prognosis. Their overexpression can correlate with aggressive tumor behavior and resistance to treatment in many contexts.
Scientific Papers found: Click to Expand⟱
2890- HNK,    SIRT3 activation promotes enteric neurons survival and differentiation
*SIRT3↑, *antiOx↑, *neuroP↑,
2891- HNK,    Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs
- Review, Var, NA
AntiCan↑, Inflam↓, antiOx↑, selectivity↑, *toxicity↓, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, TumMeta↓, NADPH↓, MMP2↓, MMP9↓, p‑mTOR↓, EGFR↓, EMT↓, SIRT1↑, SIRT3↑, EZH2↓, Snail↓, Vim↓, N-cadherin↓, E-cadherin↑, COX2↓, NF-kB↓, *ROS↓, Ca+2↑, ROS↑,
2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, *neuroP↑, *BBB↑, *ROS↓, *Keap1↑, *NRF2↑, *Casp3↓, *SIRT3↑, *Rho↓, *ERK↓, *NF-kB↓, angioG↓, RAS↓, PI3K↓, Akt↓, mTOR↓, *memory↑, *Aβ↓, *PPARγ↑, *PGC-1α↑, NF-kB↓, Hif1a↓, VEGF↓, HO-1↓, FOXM1↓, p27↑, P21↑, CDK2↓, CDK4↓, CDK6↓, cycD1/CCND1↓, Twist↓, MMP2↓, Rho↑, ROCK1↑, TumCMig↓, cFLIP↓, BMPs↑, OCR↑, ECAR↓, *AntiAg↑, *cardioP↑, *antiOx↑, *ROS↓, P-gp↓,
2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiCan↑, TumCP↑, TumAuto↑, Apoptosis↑, *BioAv↑, *neuroP↑, *NF-kB↑, MAPK↑, GPx4↑, Tf↑, BAX↑, Bcl-2↓, antiOx↑, Hif1a↓, Ferroptosis↑,
2071- HNK,    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient
- Review, Nor, HaCaT
*ROS↓, *antiOx↑, *AntiAge↑, *MMP↑, *ECAR↓, *Glycolysis↓, *PAR-2↓, *CXCL12↑, *BMAL1↑, *mt-ROS↓, *OXPHOS↓,
2872- HNK,    Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis
- in-vivo, ALS, NA - NA, Stroke, NA - NA, AD, NA - NA, Park, NA
*eff↑, *ROS↓, *GSH↑, *NRF2↑, *motorD↑, *OS↑, *neuroP↑, *BBB↑, *cognitive↑, *eff↑, *antiOx↑, *Cyt‑c↑, *PGC-1α↑,
2873- HNK,    Honokiol Alleviates Oxidative Stress-Induced Neurotoxicity via Activation of Nrf2
- in-vitro, Nor, PC12
*neuroP↑, *GSH↑, *HO-1↑, *NADPH↑, *Trx1↑, *TrxR1↑, *NRF2↑, *ROS↓, *antiOx↑, *BBB↑, Dose↓,
2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
*P-gp↓, *ROS↓, *TNF-α↓, *IL10↓, *IL6↓, eIF2α↑, CHOP↑, GRP78/BiP↑, BAX↑, cl‑Casp9↑, p‑PERK↑, ER Stress↑, Apoptosis↑, MMPs↓, cFLIP↓, CXCR4↓, Twist↓, HDAC↓, BMPs↑, p‑STAT3↓, mTOR↓, EGFR↓, NF-kB↓, Shh↓, VEGF↓, tumCV↓, TumCMig↓, TumCI↓, ERK↓, Akt↓, Bcl-2↓, Nestin↓, CD133↓, p‑cMET↑, RAS↑, chemoP↑, *NRF2↑, *NADPH↓, *p‑Rac1↓, *ROS↓, *IKKα↑, *NF-kB↓, *COX2↓, *PGE2↓, *Casp3↓, *hepatoP↑, *antiOx↑, *GSH↑, *Catalase↑, *RenoP↑, *ALP↓, *AST↓, *ALAT↓, *neuroP↑, *cardioP↑, *HO-1↑, *Inflam↓,
2867- HNK,    Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway
- in-vitro, Nor, C2C12
*antiOx↑, *ROS↓, *Bcl-2↑, *BAX↓, Casp9∅, Casp3∅, cl‑PARP∅, Cyt‑c?,
2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, CDK2↓, EMT↓, MMPs↓, AMPK↑, TumCI↓, TumCMig↓, TumMeta↓, VEGFR2↓, *antiOx↑, *Inflam↓, *BBB↑, *neuroP↑, *ROS↓, Dose↝, selectivity↑, Casp3↑, Casp9↑, NOTCH1↓, cycD1/CCND1↓, cMyc↓, P21?, DR5↑, cl‑PARP↑, P53↑, Mcl-1↑, p65↓, NF-kB↓, ROS↑, JNK↑, NRF2↑, cJun↑, EF-1α↓, MAPK↓, PI3K↓, mTORC1↓, CSCs↓, OCT4↓, Nanog↓, SOX4↓, STAT3↓, CDK4↓, p‑RB1↓, PGE2↓, COX2↓, β-catenin/ZEB1↑, IKKα↓, HDAC↓, HATs↑, H3↑, H4↑, LC3II↑, c-Raf↓, SIRT3↑, Hif1a↓, ER Stress↑, GRP78/BiP↑, cl‑CHOP↑, MMP↓, PCNA↓, Zeb1↓, NOTCH3↓, CD133↓, Nestin↓, ATG5↑, ATG7↑, survivin↓, ChemoSen↑, SOX2↓, OS↑, P-gp↓, Half-Life↓, Half-Life↝, eff↑, BioAv↓,
4521- MAG,  HNK,    Safety and Toxicology of Magnolol and Honokiol
- Review, Nor, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓,
4526- MAG,  HNK,    Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis
- Review, Var, NA
*antiOx↑, *Inflam↓, *Bacteria↓, *toxicity↓, AntiTum↑, Apoptosis↑, DR5↝,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Ferroptosis↑, 1,   GPx4↑, 1,   HO-1↓, 1,   NRF2↑, 1,   ROS↑, 2,   SIRT3↑, 2,  

Metal & Cofactor Biology ⓘ

Tf↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,   OCR↑, 1,   c-Raf↓, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   ATG7↑, 1,   cMyc↓, 1,   ECAR↓, 1,   NADPH↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 3,   BAX↑, 2,   Bcl-2↓, 2,   Casp3↑, 1,   Casp3∅, 1,   Casp9↑, 1,   Casp9∅, 1,   cl‑Casp9↑, 1,   cFLIP↓, 2,   Cyt‑c?, 1,   DR5↑, 1,   DR5↝, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↑, 1,   p27↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   EZH2↓, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   cl‑CHOP↑, 1,   eIF2α↑, 1,   ER Stress↑, 2,   GRP78/BiP↑, 2,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   LC3II↑, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,   cl‑PARP↑, 1,   cl‑PARP∅, 1,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21?, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 2,   p‑cMET↑, 1,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 1,   FOXM1↓, 1,   HDAC↓, 2,   mTOR↓, 2,   p‑mTOR↓, 1,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 2,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 2,   RAS↓, 1,   RAS↑, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 1,   p‑STAT3↓, 1,  

Migration ⓘ

Ca+2↑, 1,   E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 1,   MMPs↓, 2,   N-cadherin↓, 1,   Rho↑, 1,   ROCK1↑, 1,   Snail↓, 1,   SOX4↓, 1,   TumCI↓, 2,   TumCMig↓, 3,   TumCP↑, 1,   TumMeta↓, 2,   Twist↓, 2,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   EGFR↓, 2,   Hif1a↓, 3,   VEGF↓, 2,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   CXCR4↓, 1,   IKKα↓, 1,   Inflam↓, 1,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 1,   Dose↓, 1,   Dose↝, 1,   eff↑, 1,   Half-Life↓, 1,   Half-Life↝, 1,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

BMPs↑, 2,   EGFR↓, 2,   EZH2↓, 1,   FOXM1↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 2,   AntiTum↑, 1,   chemoP↑, 1,   OS↑, 1,  
Total Targets: 135

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 10,   Catalase↑, 1,   GSH↑, 3,   HO-1↑, 2,   Keap1↑, 1,   NRF2↑, 4,   OXPHOS↓, 1,   ROS↓, 10,   mt-ROS↓, 1,   SIRT3↑, 2,   Trx1↑, 1,   TrxR1↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↑, 1,   PGC-1α↑, 2,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   BMAL1↑, 1,   ECAR↓, 1,   Glycolysis↓, 1,   NADPH↓, 1,   NADPH↑, 1,   PPARγ↑, 1,  

Cell Death ⓘ

BAX↓, 1,   Bcl-2↑, 1,   Casp3↓, 2,   Cyt‑c↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,  

Migration ⓘ

AntiAg↑, 1,   CXCL12↑, 1,   p‑Rac1↓, 1,   Rho↓, 1,  

Barriers & Transport ⓘ

BBB↑, 4,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IKKα↑, 1,   IL10↓, 1,   IL6↓, 1,   Inflam↓, 4,   NF-kB↓, 2,   NF-kB↑, 1,   PAR-2↓, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AST↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

AntiAge↑, 1,   cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 1,   memory↑, 1,   motorD↑, 1,   neuroP↑, 7,   OS↑, 1,   RenoP↑, 1,   toxicity↓, 3,  

Infection & Microbiome ⓘ

Bacteria↓, 2,  
Total Targets: 61

Scientific Paper Hit Count for: antiOx, anti-oxidant activities
12 Honokiol
2 Magnolol
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:94  Target#:1103  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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