Honokiol 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 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">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

Honokiol — a small, lipophilic biphenolic neolignan isolated principally from the bark, seed cones, and leaves of Magnolia species, especially Magnolia officinalis. It is a natural-product small molecule rather than a standardized Magnolia extract; the standard abbreviation is HNK. Honokiol crosses biological membranes readily and has documented CNS penetration, but its pharmaceutical development is constrained by extremely poor aqueous solubility, rapid metabolism, and low/variable oral systemic exposure. Cancer research is dominated by cell and animal studies, although an oral Phase I window-of-opportunity study in patients with resectable early-stage non-small-cell lung cancer is now enrolling.

Primary mechanisms (ranked):

  1. Mitochondrial targeting and respiratory Complex I inhibition, producing mitochondrial dysfunction, loss of membrane potential, energetic stress, and intrinsic apoptosis in susceptible cancer cells.
  2. Suppression of oncogenic survival signaling, particularly STAT3 and PI3K/AKT/mTOR, with additional inhibition of EGFR and context-dependent MAPK signaling.
  3. Induction of mitochondrial ROS and oxidative stress in cancer cells as a major stress-amplifying mechanism; in nonmalignant tissues honokiol can instead activate antioxidant and mitochondrial-protective programs including SIRT3 and NRF2.
  4. Suppression of NF-κB-dependent inflammatory and prosurvival transcription, contributing to apoptosis, reduced inflammatory signaling, and treatment sensitization.
  5. Suppression of EMT, migration, invasion, cancer-stem-cell phenotypes, and angiogenic signaling through STAT3, Wnt/β-catenin, EGFR, HIF-1α, VEGF, Snail/Slug, MMPs, and related networks.
  6. Metabolic inhibition, including suppression of HIF-1α-driven glycolysis, GLUT1, HK2, LDHA and PDK signaling, with reduced glycolytic flux and ATP availability in several tumor models.
  7. Induction of ER stress, autophagy, cell-cycle arrest and, in selected tumor contexts, ferroptosis; these effects appear downstream or context-dependent rather than universal initiating mechanisms.
  8. Chemosensitization, radiosensitization and immune-modulatory effects have been demonstrated preclinically, including enhancement of selected targeted therapies and PD-1/PD-L1-directed approaches.

Bioavailability / PK relevance: Native honokiol is highly lipophilic and poorly water-soluble, limiting conventional oral and intravenous delivery. It undergoes extensive metabolic clearance, including conjugation, and systemic exposure after ordinary oral formulations may be substantially lower than concentrations commonly used experimentally. Liposomes, nanoemulsions, micelles, nanoparticles and other delivery systems can substantially improve solubility and exposure. A validated pharmacokinetic study of injectable liposomal honokiol has been reported, but clinically established human anticancer PK targets have not yet been defined.

In-vitro vs systemic exposure relevance: Many anticancer studies use approximately 10–60 µM honokiol, with some models requiring still higher concentrations. These concentrations should not automatically be considered achievable following conventional oral supplementation because oral bioavailability is limited and human tumor exposure has not been established. The current Phase I lung-cancer study is therefore important for defining human tolerability, systemic exposure and pharmacodynamic effects rather than demonstrating established therapeutic efficacy.

Clinical evidence status: Predominantly preclinical. Extensive in-vitro and animal anticancer evidence exists across multiple tumor types. Human anticancer efficacy has not been established. A Phase I oral honokiol study in approximately 15 patients with early-stage resectable NSCLC is currently listed by Houston Methodist as enrolling; treatment is given before surgery primarily to determine safety and maximum tolerated dose. Honokiol is not an FDA-approved anticancer drug.

Safety / translation: Preclinical toxicology has generally suggested a comparatively broad therapeutic window, but concentrated honokiol should not be assumed equivalent to historical consumption of Magnolia bark preparations. Potential pharmacokinetic interactions, formulation-dependent exposure, and insufficient controlled human safety data remain major translational limitations. FDA records identify Magnolia cortex extract containing honokiol as having been submitted through the New Dietary Ingredient notification process, but this does not constitute approval of honokiol for cancer treatment.

Honokiol Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial Complex I and intrinsic apoptosis ↓ Complex I; ↓ ΔΨm; ↓ respiration; ↑ cytochrome-c; ↑ caspases ↔ or mitochondrial protection (context-dependent) P/R Mitochondria-directed cytotoxicity A particularly strong mechanistic feature of honokiol; mitochondrial accumulation and respiratory inhibition can precede downstream apoptotic signaling.
2 STAT3 survival and stemness signaling ↓ STAT3; ↓ p-STAT3; ↓ mitochondrial STAT3 ↔ (context-dependent) R/G Loss of survival, proliferation and stemness signaling Relevant across several cancer models and linked to reduced CSC phenotype, EMT and resistance.
3 PI3K AKT mTOR signaling ↓ PI3K; ↓ AKT; ↓ mTOR ↔ or adaptive modulation R/G Growth and anabolic suppression Frequently observed and contributes to apoptosis, metabolic stress and treatment sensitization.
4 Mitochondrial ROS increase ↑ ROS; ↑ mt-ROS (secondary) ↓ ROS or ↔ (context-dependent) P/R Oxidative stress amplification Cancer-cell ROS elevation often accompanies mitochondrial respiratory disruption. Honokiol can instead act antioxidatively in nonmalignant tissues.
5 NF-κB inflammatory and survival signaling ↓ NF-κB; ↓ COX-2; ↓ inflammatory survival signaling ↓ pathological inflammatory signaling R/G Reduced inflammatory and prosurvival transcription Provides both anticancer and tissue-protective effects depending on cellular context.
6 EMT invasion and metastasis ↓ EMT; ↓ Snail; ↓ Slug; ↓ MMP2; ↓ MMP9; ↑ E-cadherin ↔ G Reduced migration, invasion and metastasis Supported across breast, lung, renal, pancreatic and other tumor models.
7 Cancer stem cell signaling ↓ CSCs; ↓ CD133; ↓ SOX2; ↓ OCT4; ↓ Nestin; ↓ Wnt/β-catenin ↔ G Reduced tumor-initiating and resistant cell phenotype Closely overlaps STAT3, EGFR, Notch and Wnt pathway inhibition.
8 HIF-1α glycolytic metabolism ↓ HIF-1α; ↓ GLUT1; ↓ HK2; ↓ LDHA; ↓ PDK1; ↓ ECAR; ↓ glycolysis ↔ (context-dependent) G Reduced glycolytic flux and ATP production Especially relevant in glycolysis-dependent and hypoxic tumors.
9 EGFR and receptor tyrosine kinase signaling ↓ EGFR; ↓ downstream AKT and ERK ↔ R/G Growth-factor signal suppression Honokiol can also impair EGFR stability through HDAC6/HSP90-associated mechanisms.
10 Angiogenesis and hypoxia response ↓ VEGF; ↓ HIF-1α; ↓ angiogenesis ↔ G Reduced tumor vascular support Largely downstream of HIF-1α, NF-κB and growth-factor suppression.
11 ER stress and calcium signaling ↑ ER stress; ↑ GRP78; ↑ CHOP; ↑ Ca²⁺ (model-dependent) ↔ or protective stress response R/G Proteotoxic stress and apoptosis Prominent in selected osteosarcoma and other experimental models rather than universal across cancers.
12 Cell cycle regulation ↑ G0/G1 or G2/M arrest; ↓ cyclin D1; ↓ CDK2; ↓ CDK4; ↓ CDK6 ↔ G Cytostatic growth suppression Checkpoint phenotype depends on tumor type and upstream signaling context.
13 Ferroptosis and lipid peroxidation ↑ ferroptosis; ↑ lipid peroxidation; GPX4 modulation (model-dependent) ↔ G Alternative regulated cell death GPX4 direction is not uniform across studies; HMOX1-associated and GPX4-associated ferroptosis have both been reported.
14 NRF2 antioxidant response ↔ or ↑ (model-dependent) ↑ NRF2; ↑ antioxidant defenses R/G Secondary tissue-protective redox response NRF2 activation is more compelling as a normal-cell or neuroprotective mechanism than as a core anticancer mechanism.
15 SIRT3 mitochondrial protection ↑ SIRT3 (context-dependent) ↑ SIRT3; ↑ mitochondrial resilience; ↓ oxidative injury R/G Context-dependent mitochondrial regulation Important for cardioprotective and neuroprotective effects; its cancer role can vary with tumor context because SIRT3 itself has context-dependent tumor biology.
16 Chemosensitization and targeted-therapy sensitization ↑ treatment sensitivity (drug-dependent) ↔ or tissue protection G Combination-treatment enhancement Preclinical evidence includes chemotherapy, cetuximab, mTOR inhibitors and immune-checkpoint strategies.
17 Radiosensitization ↑ radiosensitivity (model-dependent) ↔ or radioprotection (context-dependent) G Greater radiation response This apparent duality emphasizes cell type, dose, redox state and treatment timing.
18 Clinical Translation Constraint ↓ achievable exposure with conventional formulations Systemic safety incompletely characterized in humans G Bioavailability and evidence limitation Poor aqueous solubility, extensive metabolism, uncertain human tumor exposure and lack of efficacy trials remain central constraints; Phase I investigation is underway.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr



Honokiol and Alzheimer’s disease: Honokiol has meaningful but entirely preclinical relevance to Alzheimer’s disease and related neurodegeneration. Its lipophilicity permits CNS penetration, and experimental studies indicate reductions in oxidative stress, neuroinflammation, excitotoxicity and Aβ-associated toxicity together with preservation of mitochondrial function. SIRT3, NRF2, PPAR/PGC-1α signaling and restoration of microglial metabolic competence are among the more plausible mechanistic axes. No convincing clinical evidence currently establishes honokiol as an AD treatment.

Evidence level: Preclinical only. Cell and animal studies support neuroprotective and cognition-related effects, but human AD efficacy, dose-response relationships and long-term neurological safety have not been demonstrated.

Honokiol Alzheimer’s-Relevant Mechanisms

Rank Pathway / Axis Modulation Primary Effect Notes / Interpretation
1 Mitochondrial function and SIRT3 ↑ SIRT3; ↑ mitochondrial function; ↑ ΔΨm Mitochondrial resilience One of the strongest mechanistic links between honokiol and neuronal protection.
2 Oxidative stress and NRF2 ↓ ROS; ↑ NRF2; ↑ antioxidant defenses Reduced oxidative injury Direction differs from the pro-oxidant stress frequently induced by honokiol in cancer cells.
3 Microglial metabolism and phagocytosis ↑ PPARα; ↑ PGC-1α; ↑ OXPHOS; ↑ phagocytosis Improved microglial metabolic function Experimental evidence suggests reversal of dysfunctional metabolic programming can restore microglial clearance capacity.
4 Amyloid beta toxicity ↓ Aβ-associated toxicity Neuroprotection Supported primarily by experimental models; evidence for modifying human amyloid pathology is absent.
5 Neuroinflammation ↓ NF-κB; ↓ TNF-α; ↓ IL-1β Reduced inflammatory injury Likely overlaps the general anti-inflammatory pharmacology of honokiol.
6 Excitotoxic calcium signaling ↓ pathological Ca²⁺ signaling Reduced excitotoxic neuronal injury Reported neuroprotective actions include modulation of glutamatergic signaling and intracellular calcium overload.
7 Clinical Translation Constraint No demonstrated human AD efficacy Preclinical evidence only BBB penetration is pharmacologically favorable but does not establish an effective or safe human CNS dose.


Scientific Papers found: Click to Expand⟱
2896- HNK,    Honokiol inhibits hypoxia-inducible factor-1 pathway
- in-vivo, Colon, CT26
Hif1a↓, Our data suggest that honokiol can exert its anticancer activity as a HIF-1α inhibitor by reducing HIF-1α protein level and suppressing the hypoxia-related signaling pathway.
RadioS↑, The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation

4240- HNK,    Honokiol Exerts Antidepressant Effects in Rats Exposed to Chronic Unpredictable Mild Stress by Regulating Brain Derived Neurotrophic Factor Level and Hypothalamus–Pituitary–Adrenal Axis Activity
- in-vivo, NA, NA
*BDNF↑, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus.

4239- HNK,    Honokiol reverses depressive-like behavior and decrease in brain BDNF levels induced by chronic corticosterone injections in mice
- in-vivo, NA, NA
*Mood↑, Treatment of the mice with honokiol significantly suppressed the depression-like behavior and increased brain BDNF levels (P < 0.01) in CORT-treated mice.
*BDNF↑,

4238- HNK,    Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint
- Review, AD, NA - NA, Park, NA
*BDNF↑, honokiol treatment led to an improvement in plasma BDNF levels.
*hepatoP↑, prevented liver damage by reducing transaminase levels (ALT and AST), liver OS, and TNF-α activity in mice challenged with LPS.
*ALAT↓,
*AST↓,
*TNF-α↓,
*SIRT3↑, 0.5, 1, 2, 5, 10 and 20 μM Enhanced SIRT3 expression, reduced Aβ levels
*Aβ↓,
*Apoptosis↓, Honokiol exhibited a dose-dependent reduction in hippocampal neural apoptosis, ROS generation, and decline in the membrane potential of mitochondria caused by AβO
*ROS↓,
*MMP↑,
*Ca+2↓, Dose-dependent reduction of ROS, suppression of intracellular Ca elevation, and inhibition of caspase-3 activity
*Casp3↓,
*Ach↑, Increased extracellular acetylcholine release to 165.5 ± 5.78% of the basal level
*PPARγ↑, Increased the expression of PPARγ and PGC1α
*PGC-1α↑,
*motorD↑, Improvement of motor dysfunction due to reversal of nigrostriatal dopaminergic neuronal loss
*TNF-α↓, Attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro
*IL1β↓,

2902- HNK,  Rad,    Honokiol Mitigates Ionizing Radiation-Induced Injury by Maintaining the Redox Balance of the TrxR/Trx System
- in-vitro, Nor, BEAS-2B
*TrxR1↑, HKL pre-exposure significantly increased the expressions of TrxR1 and Trx proteins in general, in particular at doses ranging between 0.05 and 5 µM HKL
*Trx↑,
*radioP↑, Overall, the findings presented here demonstrate that HKL has the potential to be a novel radioprotector capable of cellular protection against radiation-induced injuries
*ROS↓, Compared to the IR group, there was a significant decrease in the ROS levels of the HKL+IR treated group

2901- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
*mitResp↑, mice treated with Honokiol showed enhanced mitochondrial respiration
*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat cardiomyocytes
*Inflam↓, Honokiol repressed cardiac inflammatory responses and oxidative stress in mice subjected to Dox treatment.
*ROS↓,
*cardioP↑, We conclude that Honokiol protects the heart from Dox-cardiotoxicity
*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice
*LDH↓, Furthermore, Honokiol treatment reduced the Dox-induced elevation of lactate dehydrogenase (LDH) activity (Fig. 6D) in mice subjected to acute Dox treatment.

2900- HNK,    The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance
- Review, Var, NA
SIRT3↑, Honokiol blocks the growth of lung cancer cells by activating SIRT3 to inhibit HIF-1α expression
Hif1a↓,
ChemoSen↑, and also be used as adjuvant chemotherapy to prevent doxorubicin-induced cardiotoxicity in tumors transplanted mice
chemoP↑,

2899- HNK,    SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus
- in-vivo, Nor, NA
*memory↑, Honokiol attenuated surgery-induced memory loss and neuronal apoptosis, decreased neuroinflammatory response, and ameliorated oxidative damage in hippocampus.
*Inflam↓,
*ROS↓,
neuroP↑,
SIRT3↑, HNK increased SIRT3 expression and thus decreased the acetylation of superoxide dismutase 2 (SOD2).
ac‑SOD2↓,

2898- HNK,    Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism
- in-vitro, GC, AGS - in-vitro, GC, NCI-N87 - in-vitro, BC, MGC803 - in-vitro, GC, SGC-7901
TumCP↓, Honokiol suppressed cell proliferation via increasing cell apoptosis, invasion, and migration with dose dependence.
Apoptosis↑,
TumCI↓,
TumCMig↓,
HER2/EBBR2↓, HER2 protein expression was significantly depressed in honokiol-treated groups
TumCCA↑, results show that Hon kept the cell cycle in G1 phase, which might be the cause of the cell apoptosis rate increase.
PI3K↓, PI3K, AKT, and MMP-9 protein and mRNA expression of Hon-treated groups were significantly suppressed
Akt↓,
MMP9↓,
P21↑, increase P21 protein and gene expression

2897- HNK,    Honokiol Inhibits Proliferation, Invasion and Induces Apoptosis Through Targeting Lyn Kinase in Human Lung Adenocarcinoma Cells
- in-vitro, Lung, PC9 - in-vitro, Lung, A549
TumCP↓, Honokiol Inhibits Cell Proliferation in Both A549 Cells and PC-9 Cells
Apoptosis↑, Honokiol Induces Apoptosis in PC-9 Cells
EGFR↓, Honokiol Suppresses Lyn Kinase and EGFR Signaling Pathway in PC-9 Cells
PI3K↓, led to a reduction of EGFR/PI3K/AKT and STAT3, and their phosphorylation status.
Akt↓,
STAT3↓,
TumCI↓, honokiol inhibits PC-9 cell proliferation, invasion and induces apoptosis through targeting Lyn kinase and Lyn-mediated EGFR signaling pathway.
TNF-α↑, Honokiol has efficacy to enhance the activation of TNF-α, in this way, honokiol inhibits activation of NF-κB and Akt. As a result, honokiol dramatically decreases expression level of NF-κB target genes, such as VEGF, MMP-9, and COX-2.
NF-kB↓,
VEGF↓,
MMP9↓,
COX2/PTGS2↓,

4241- HNK,    Effects of Honokiol on Neurological Injury and Cognitive Function in Mice with Intracerebral Hemorrhage by Regulating BDNF-TrkB-CREB Signaling Pathway
- in-vivo, Stroke, NA
*Apoptosis↓, Honokiol may alleviate hippocampal neuronal apoptosis and damage, and improve cognitive dysfunction in ICH mice by activating the BDNF-TrkB-CREB signaling pathway.
*cognitive↑,
*BDNF↑,
*TrkB↑,
*CREB↑,

2895- HNK,    Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
- in-vitro, Lung, PC9
eff↑, Mito-HNK is >100-fold more potent than HNK in inhibiting cell proliferation
TumCP↓,
mt-ROS↑, inhibiting mitochondrial complex ǀ, stimulating reactive oxygen species generation, oxidizing mitochondrial peroxiredoxin-3, and suppressing the phosphorylation of mitoSTAT3
Prx3↑,
mt-STAT3↓,
*toxicity∅, Mito-HNK showed no toxicity and targets the metabolic vulnerabilities of primary and metastatic lung cancers.
selectivity↑,
ChemoSen↑, combination with standard chemotherapeutics.

2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
*BBB↑,
*ROS↓, fig 2
*Keap1↑,
*NRF2↑,
*Casp3↓,
*SIRT3↑,
*Rho↓,
*ERK↓,
*NF-kB↓,
angioG↓,
RAS↓,
PI3K↓,
Akt↓,
mTOR↓,
*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
*PGC-1α↑,
NF-kB↓, activation of NFjB was suppressed by HNK via suppression of nuclear translocation and phosphorylation of the p65 subunit and further instigated apoptosis by enhancing TNF-a
Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
HO-1↓,
FOXM1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
p27/CDKN1B↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
P21↑,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
MMP2↓,
Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
ROCK1↑,
TumCMig↓,
cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
BMPs↑, HNK treatment increases the expression of BMP7 protein
OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
ECAR↓,
*AntiAg↑, It also suppresses the platelet aggregation
*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
*antiOx↑,
*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
P-gp/ABCB1↓, The expres- sion of P-gp at mRNA and protein levels is reduced in HNK treatment on human MDR and MCF-7/ADR breast cancer cell lines

2893- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
*mitResp↑, Oxygen consumption in freshly isolated mitochondria from mice treated with Honokiol showed enhanced mitochondrial respiration.
*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat
*cardioP↑, Honokiol alleviated Dox-cardiotoxicity with improved cardiac function and reduced cardiomyocyte apoptosis
*SIRT3↑, recent study reported that Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial SIRT3
*ROS↓, Honokiol treatment depressed total ROS levels, which illustrated by the less pronounced decreased ratio of GSH/GSSG in mice
*GSH↑,
*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice

2892- HNK,    Honokiol Induces Apoptosis, G1 Arrest, and Autophagy in KRAS Mutant Lung Cancer Cells
- in-vitro, Lung, A549 - in-vitro, Lung, H460 - in-vitro, Lung, H385 - in-vitro, Nor, BEAS-2B
TumCCA↑, Honokiol was shown to induce G1 arrest and apoptosis to inhibit the growth of KRAS mutant lung cancer cells
Apoptosis↑,
SIRT3↑, we also discovered that Sirt3 was significantly up-regulated in honokiol treated KRAS mutant lung cancer cells,
Hif1a↓, leading to destabilization of its target gene Hif-1α, (accompanied by a reduction of Hif-1a expression)
selectivity↑, but it showed low toxicity to two normal lung cells (CCD19-Lu and BEAS-2B)
p‑mTOR↓, honokiol suppressed mTOR phosphorylation, leading to inhibition of P70S6K kinase activity,
p70S6↓,

2891- HNK,    Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs
- Review, Var, NA
AntiCan↑, honokiol possesses anti-carcinogenic, anti-inflammatory, anti-oxidative, anti-angiogenic as well as inhibitory effect on malignant transformation of papillomas to carcinomas in vitro and in vivo animal models without any appreciable toxicity.
Inflam↓,
antiOx↑,
selectivity↑,
*toxicity↓,
cycD1/CCND1↓, honokiol resulted in inhibition of UVB-induced expression levels of cyclins (cyclins D1, D2, and E) and CDKs in skin tumors
cycE/CCNE↓,
CDK2↓,
CDK4↓,
TumMeta↓, Honokiol Inhibits Metastatic Potential of Melanoma Cells
NADPH↓, Honokiol not only reduces the NADPH oxidase activity
MMP2↓, honokiol treatment reduces the expression of MMP-2 and MMP-9
MMP9↓,
p‑mTOR↓, honokiol caused significant downregulation of mTOR phosphorylation
EGFR↓, honokiol decreases the expression levels of total EGFR
EMT↓, honokiol effectively inhibits EMT in breast cancer cells
SIRT1↑, onokiol increases the expressions of SIRT1 and SIRT3,
SIRT3↑,
EZH2↓, depletion of EZH2 by honokiol treatment inhibited cell proliferation
Snail↓, significantly down regulates Snail, vimentin, N-cadherin expression, and upregulates cytokeratin-18 and E-cadherin expression
Vim↓,
N-cadherin↓,
E-cadherin↑,
COX2/PTGS2↓, honokiol as an inhibitor of COX-2 expression
NF-kB↓, inhibited transcriptional activity of NF-jB,
*ROS↓, Inhibition of UVR-induced inflammatory mediators as well as ROS by honokiol treatment contributes to the prevention of UVR-induced skin tumor development
Ca+2↑, excessive influx of cytosolic calcium ion into the mitochondria triggers dysfunction of the mitochon- drial membrane permeabilization with mitochondrial ROS induction
ROS↑,

2890- HNK,    SIRT3 activation promotes enteric neurons survival and differentiation
*SIRT3↑, Honokiol, a naturally occurring compound, is an activator of Sirtuin-3 (SIRT3) that has antioxidant activity.
*antiOx↑,
*neuroP↑, Our data supports a neuroprotective effect of honokiol and its derivative

2889- HNK,  doxoR,    Honokiol, an activator of Sirtuin-3 (SIRT3) preserves mitochondria and protects the heart from doxorubicin-induced cardiomyopathy in mice
- in-vivo, Nor, NA
*SIRT3↑, We have recently identified honokiol (HKL) as an activator of SIRT3
chemoP↑, HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin.
*cardioP↑, mice that received doxorubicin plus HKL showed preserved cardiac function, compared to doxorubicin and vehicle treated mice
mtDam↑, HKL-mediated activation of SIRT3 prevented Doxorubicin induced ROS production, mitochondrial damage and cell death in rat neonatal cardiomyocytes
ROS↑,
*ROS↓, We found that cells treated with HKL suppressed doxorubicin-induced ROS levels
*MMP↑, HKL preserves mitochondrial membrane potential.

960- HNK,    Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth
- vitro+vivo, BC, MCF7 - vitro+vivo, BC, MDA-MB-231
OCR↑, which resulted in an increase in OCR and a decrease in ECAR, glucose uptake, lactic acid production and ATP production.
ECAR↓,
GlucoseCon↓, decreased glucose uptake, lactate production and ATP production in cancer cells.
lactateProd↓,
ATP↓,
Glycolysis↓,
Hif1a↓,
GLUT1↓,
HK2↓,
PDK1 / PDPK1↓,
Apoptosis↑,
LDHA↓, upregulation of LDHA mediated by HIF-1α promoted the formation of lactic acid from pyruvate, which contributed to the acidification of the tumor microenvironment. Our experimental observation results showed that these changes were reversed by HNK

2887- HNK,    Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming
- in-vitro, AD, BV2
*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
*ATP↑,
*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
*MMP↑,
*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
*PGC-1α↑,

7458- HNK,    Honokiol induces ferroptosis in ovarian cancer cells through the regulation of YAP by OTUB2
- in-vitro, Ovarian, OVCAR-3
TumCP↓, Honokiol has an inhibitory effect on proliferation, invasion, and survival of cancer cells in vitro and in vivo.
TumCI↓,
Ferroptosis↑, Honokiol was capable of inducing ferroptosis in OVCA cells.
YAP/TEAD↓, honokiol induced ferroptosis in OVCA cells via repression of YAP signaling pathway through binding to OTUB2.
OTUB2↓,

7468- HNK,    Honokiol and Its Emerging Role in Breast Cancer Therapy
- Review, BC, NA
*ROS↓, HNK inhibits essential oncogenic pathways and reduces oxidative stress, inflammation, metabolic reprogramming, and cancer stemness.
*Inflam↓,
CSCs↓,
ChemoSen↑, HNK demonstrates synergistic activity with chemotherapy, endocrine therapy, targeted therapy, and immune checkpoint inhibitors, increasing sensitivity to treatment across models of ER+, PR+, and HER2+ BrCas, as well as triple-negative breast cancers
BioAv↑, Nanotechnological delivery systems enhance the solubility, bioavailability, and intratumoral accumulation of HNK, increasing its translational capacity.
ROS↑, HNK increases intracellular reactive oxygen species (ROS) levels in cancer cells, coinciding with a time-dependent loss of mitochondrial membrane potential (ΔΨm), indicating that ROS production is closely linked to mitochondrial damage
MMP↓,
mtDam↑,
TumCCA↑, HNK causes G0/G1 cell cycle arrest by downregulating cyclin D1 and CDK4, as well as promoting intrinsic apoptosis-like pathways marked by increases in caspase-3 and caspase-9 activities
cycD1/CCND1↓,
CDK4↓,
Casp3↑,
Casp9↑,
Bcl-2↓, reducing the anti-apoptotic Bcl-2 and Bcl-xL, and increasing the pro-apoptotic Bax
Bcl-xL↓,
BAX↑,
p‑STAT3↓, HNK suppresses the phosphorylation of STAT3 in MDA-MB-231
AMPK↑, HNK was found to activate the LKB1–AMPK axis and induce miR-34a expression in MCF7, SKBR3, and SUM149 cells, thereby inhibiting EMT, stemness, and oncogenic leptin signaling in an LKB1-dependent manner
miR-34a↑,
EMT↓,
HH↓, HNK can induce apoptosis by suppressing essential components of the Hh pathway, including SHH [28], Gli1, and Ptch1 [26], as well as downregulating NF-κB
Shh↓,
Gli1↓,
PTCH1↓,
NF-kB↓,
TNF-α↓, reduces the production of inflammatory cytokines, including TNF-α and IL-6
IL6↓,
Glycolysis↓, HNK suppresses HIF-1α-controlled glycolysis by downregulating glycolytic metabolic enzymes, disrupting glucose uptake, and inhibiting tumor growth.
GlucoseCon↓,
BioAv↓, This limitation is primarily attributed to pharmacokinetic challenges, including poor aqueous solubility, low oral bioavailability, rapid metabolism, and the lack of standardized dosing regimens,
BioAv↓, Preclinical studies demonstrate that following oral administration at 40 mg/kg, HNK is rapidly absorbed (Tmax ≈ 20 min) but exhibits low systemic exposure [75], due to extensive first-pass metabolism and high hepatic extraction
Half-Life↝, While the plasma elimination half-life is moderately prolonged (t½ ≈ 290 min),

7467- HNK,    Honokiol regulates ovarian cancer cell malignant behavior through YAP/TAZ pathway modulation
- vitro+vivo, Oral, NA
tumCV↓, HNK exerted inhibitory effects on the viability and proliferative capacity of OVCA cells, elicited apoptotic responses, curtailed the migratory and invasive tendencies of cells, and downregulated the YAP/TAZ pathway
TumCP↓,
TumCMig↓,
TumCI↓,
YAP/TEAD↓,
TAZ↓,
TumCG↓, Experiments in vivo confirmed that HNK inhibited OVCA tumor growth.

7466- HNK,  PDT,  MET,    Enhanced integrated therapy for breast cancer employing Honokiol-loaded mesoporous polydopamine nanoparticles in conjunction with photothermal effects and low-dose metformin
- in-vitro, BC, NA
TumCD↓, Our in vitro studies demonstrated that the nanosystem precisely targeted and penetrated breast cancer cells, resulting in significant cell death.
Dose↝, This tumor-inhibiting effect was due to the combined action of the encapsulated HK, free Met, and the photothermal effect induced by near-infrared laser irradiation.
cl‑Casp3↑, This combination potently stimulates the expression of cleaved caspase-3 and cleaved PARP proteins, ultimately triggering cell apoptosis and effectively curbing tumor proliferation.
cl‑PARP↑,
Apoptosis↑,
TumCP↓,

7465- HNK,    Aptamer-modified GSH-degradable honokiol polyprodrug nanoparticles for ovarian cancer-specific targeting therapy
- in-vitro, Ovarian, NA
Dose↝, Herein, a glutathione (GSH)-sensitive HK polyprodrug was prepared using HK as the backbone. resulting polyprodrug was assembled into nanoparticles (NPs) in water
eff↑, A/P-PHK NP40 also demonstrated a greater cell growth inhibition effect in ovarian cancer cells compared to free HK and control HK NPs.

7464- HNK,    Bioinformatics and In Vitro Study Reveal ERα as The Potential Target Gene of Honokiol to Enhance Trastuzumab Sensitivity in HER2+ Trastuzumab-Resistant Breast Cancer Cells
- in-vitro, BC, HCC1954
tumCV↓, Honokiol showed a potent cytotoxicity activity with an IC50 of 41.05 μM and 69.61 μM in parental HCC1954 and TR-HCC1954 cell line respectively.
ChemoSen↑, Furthermore, the combination of honokiol and trastuzumab resulted in significant differences in cytotoxicity in TR-HCC1954 cells at specific concentrations

7463- HNK,    Honokiol Inhibits Colorectal Cancer Cell Growth: Involvement of Hsp27 as a Molecular Target
- in-vitro, CRC, NA
TumCG↓, HK dose-dependently suppressed anchorage-independent growth of CRC cells and induced G0/G1 arrest.
TumCCA↑,
Cyt‑c↑, It triggered apoptosis through cytochrome c release, PARP cleavage, and Bcl-2 downregulation.
Apoptosis↑,
cl‑PARP↑,
Bcl-2↓,
HSP27↓, HK exerts anti-cancer effects in CRC cells, associated with Hsp27 inhibition,

7461- HNK,    Honokiol: a potent chemotherapy candidate for human colorectal carcinoma
- vitro+vivo, CRC, RKO
Apoptosis↑, honokiol induced apoptosis of RKO cells in a time- and dose-dependent manner
Casp↑, At 5-10 ug/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades.
Dose↝, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h.
OS↑, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice.
*Inflam↓, honokiol has been found having a variety of pharmacological effects, such as anti-inflammatory[2], antithrombotic[3], anti-arrhythmic[4], antioxidative[5] and anxiolytic effects
*AntiThr↑,
*antiOx↑,
*Half-Life↝, intraperitoneal injection of 250 mg/kg to BALB/c mice.absorption half-life of 10.121 ± 2.761 min, and an elimination half-life of 5.218 ± 0. 461 h
TumCG↓, nhibition of solid tumor growth in nude mice bearing RKO cells

7460- HNK,    Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lb MPMs) for Improving Solubility to Enhance Oral Bioavailability
- in-vivo, Nor, NA
BioAv↝, The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol.
BioAv↝, For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.

7459- HNK,    Honokiol Exhibits Anti-Tumor Effects in Breast Cancer by Modulating the miR-148a-5p-CYP1B1 Axis
- in-vitro, BC, MDA-MB-231
TumCP↓, We found that HNK significantly inhibited proliferation and induced apoptosis on BC cell lines in a dose-dependent manner.
Apoptosis↓,
TumCMig↓, HNK treatment suppressed migration and colony formation and initiated the intrinsic apoptotic pathway specifically in MDA-MB-231 cells.
CYP1B1↓, miR-148a-5p expression was significantly up-regulated, whereas CYP1B1 expression was down-regulated following HNK treatment.
ChemoSen↑, strong synergistic effect between HNK and paclitaxel was observed in vitro.

2888- HNK,    Honokiol mediated inhibition of PI3K/mTOR pathway: A potential strategy to overcome immunoresistance in glioma, breast and prostate carcinoma without impacting T cell function
- in-vitro, Var, PC3 - in-vitro, BC, BT549
PI3K↓, decrease PI3K/mTOR pathway mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical pro-inflammatory T cell functions
mTOR↓,
Inflam↓, Honokiol has anti-inflammatory properties in T cells

7457- HNK,    Honokiol enhances the sensitivity of cetuximab in KRASG13D mutant colorectal cancer through destroying SNX3-retromer complex
- in-vitro, CRC, NA
ChemoSen↑, we revealed that the synergistic augmentation of cetuximab's sensitivity in vivo and in vitro models of KRASG13D mutant CRC in combination with honokiol.

7456- HNK,    Honokiol in the treatment of triple-negative breast cancer: a network pharmacology approach and experimental validation
- vitro+vivo, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
Apoptosis↑, Results indicated that HNK induces apoptosis in MDA-MB 231 and MDA-MB 468 cells and inhibits their migration and proliferation.
TumCMig↓,
TumCP↓,
HSP90↓, HNK targets against TNBC, including HSP90AA1, AKT1, EGFR, ERBB2, HSP90AB1, PGR, MDM2, HDAC1, NR3C1, and MAPK14.
AKT1↓,
EGFR↓,
HSP90↓,
MDM2↓,
HDAC1↓,

7455- HNK,    Honokiol in cancer: Roles in enhancing combination therapy efficacy and preventing post-transplant malignancies
- Review, Var, NA
ChemoSen↑, It enhances the efficacy of chemotherapies, such as cisplatin and paclitaxel, RTK inhibitors, such as cabozantinib and erlotinib, and mAbs, such as cetuximab.
Imm↝, honokiol aids in post-transplant cancer prevention by modulating immune responses, reducing tumor progression, and lowering the required dose of immunosuppressants, such as cyclosporine A and rapamycin.
*hepatoP↑, figure1
*cardioP↑,
*neuroP↑,
*AntiCan↑,
*Inflam↓,
*antiOx↑,
eff↑, By lowering systemic glucose levels, metformin limits the energy supply available to cancer cells, thereby inhibiting their growth and proliferation. Studies have shown that combining metformin with honokiol yields promising synergistic effects.
*TNF-α↓, potent anti-inflammatory properties, contributing to its anti-cancer effects. It inhibits the production of key pro-inflammatory cytokines, including tumor necrosis factor-alpha, IL-1 beta, and IL-6,
*IL1?,
*IL6?,

7454- HNK,    Updated progression of honokiol in lung cancer treatment
- Review, Lung, NA
AntiCan↑, Honokiol (HNK) is a biphenolic natural compound with significant anti-lung cancer properties.
eff↑, nanotechnologies have been used to modify HNK, potentially enhancing its efficacy in the treatment of lung cancer

7453- HNK,    Determination of Potential Lead Compound from Magnolia officinalis for Alzheimer's Disease through Pharmacokinetic Prediction, Molecular Docking, Dynamic Simulation, and Experimental Validation
- Study, AD, NA
*BACE/β-secretase↓, honokiol emerged as a lead structure for the inhibition of BACE1, AChE, QC, and GSK-3β in docking and molecular dynamics (MD) simulations.
*AChE↓,
*QPCT/QC↓,
*GSK‐3β↓,
*toxicity↓, honokiol acts as a multiple enzyme inhibitor with an excellent pharmacokinetic and safety profile which may provide inhibitory effects in broad-range areas including the overproduction, aggregation, and post-translational modification of Aβ

4688- HNK,    Honokiol Suppresses Renal Cancer Cells’ Metastasis via Dual-Blocking Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties through Modulating miR-141/ZEB2 Signaling
- vitro+vivo, RCC, A498
CSCs↓, honokiol suppressed renal cancer cells’ metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties
EMT↓,
TumCG↓, In addition, honokiol inhibited tumor growth in vivo
PI3K↓, Honokiol was able to attenuate PI3K/Akt/mTOR signaling by down-regulation of Akt phosphorylation and upregulation of PTEN expression
Akt↓,
mTOR↓,
p‑Akt↓,
PTEN↑,
Wnt↓, In oral cancer cells, honokiol eliminated stem-like cells and suppressed Wnt/β-Catenin Signaling
β-catenin/ZEB1↓,

4659- HNK,    Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction
- in-vitro, Oral, NA
cl‑Casp3↑, Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2.
survivin↓,
Bcl-2↓,
CD44↓, Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells
Wnt↓,
β-catenin/ZEB1↑,
EMT↓, EMT markers such as Slug and Snail were markedly suppressed by honokiol.
Slug↓,
Snail↓,
CSCs↓, Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT.
Apoptosis↑, Honokiol-Induced Apoptosis of SAS SP Cells

4523- HNK,  MAG,  BA,    Honokiol-Magnolol-Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti-PD-1 Immunotherapy in Colorectal Cancer by Triggering GSDME-Dependent Pyroptosis
- in-vitro, CRC, HCT116 - in-vitro, CRC, LoVo - in-vivo, CRC, HCT116
AntiCan↑, honokiol (H), magnolol (M), and baicalin (B) are found to exhibit a synergistic anticancer effect on CRC
eff↑, Most importantly, HMB is shown to enhance the sensitivity of CRC cells to anti‐PD‐1 immunotherapy in vivo.
TumCP↓, HMB Synergistically Inhibits Cell Proliferation and Triggers Cell Death in CRC Cells and Organoid Models
TumCCA↓, HMB treatment induced G0/G1 phase arrest, accompanied by reduced expression of cyclin D1 and p‐RB expression in both HCT116 and LoVo cells.
cycD1/CCND1↓,
Pyro↑, HMB Synergistically Induces Pyroptosis and Apoptosis
Apoptosis↑,
cl‑GSDME↑, HMB Synergistically Induces Pyroptosis by Promoting the Cleavage of GSDME
Bcl-2↓, HMB treatment reduced Bcl‐2 expression, promoted cytochrome c release from mitochondria, and activated caspase‐9
Cyt‑c↑,
Casp9↑,
TumCG↓, results demonstrate that the HMB combination synergistically inhibited tumor growth and induced pyroptosis in vivo

4522- HNK,  MAG,    Honokiol Is More Potent than Magnolol in Reducing Head and Neck Cancer Cell Growth
- in-vitro, HNSCC, FaDu
AntiCan↑, Natural compounds, like Magnolia-derived lignans—honokiol (HON) and magnolol (MAG)—can reduce cancer cell growth but retain a good safety profile and thus may show benefit as adjuvant therapeutics.
tumCV↓, We observed that HON and MAG were more potent in reducing cell viability in cisplatin persister FaDu cells, although this effect was not directly followed by increased rates of apoptosis.
eff↑, we observed that HON exerted stronger cytotoxic effects than MAG in HNSCC cells, and the difference in their anti-cancer activity was especially pronounced in cells cultured in 3D.
survivin↓, HON improved the effects of radiotherapy by targeting survivin, as shown in the in vitro and xenograft models of HNSCC
RadioS↑,

2072- HNK,    Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells
- in-vitro, Thyroid, NA
ROS↑, honokiol induced ROS activation
eff↓, and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC).

2886- HNK,    Liposomal honokiol inhibits non-small cell lung cancer progression and enhances PD-1 blockade via suppressing M2 macrophages polarization
- in-vitro, Lung, A549 - in-vitro, Lung, H460 - in-vivo, NA, NA
eff↑, Lipo-HNK, with enhanced solubility and bioavailability, demonstrated potent cytotoxicity against NSCLC cell lines.
BioAv↑,
eff↑, Lipo-HNK exhibited synergistic anti-cancer effects when combined with anti-PD-1 therapy
PI3K↓, inhibiting the PI3K/Akt
Akt↓,

2865- HNK,    Liposomal Honokiol induces ROS-mediated apoptosis via regulation of ERK/p38-MAPK signaling and autophagic inhibition in human medulloblastoma
- in-vitro, MB, DAOY - vitro+vivo, NA, NA
BioAv↓, poor water solubility of HNK results in its low bioavailability, thus limiting its wide use in clinical cancer treatments
BioAv↓, Liposomes can overcome this limitation, and liposomal HNK (Lip-HNK) has promising clinical applications in this aspect
TumCP↓, increased Lip-HNK concentration could inhibit the proliferation of DAOY and D283 cells, without exerting effects on the growth of non-tumor cells
selectivity↑,
P53↑, P53 and P21 proteins (inhibiting cell cycle progression) was increased
P21↑,
CDK4↓, Lip-HNK also downregulated the expression of CDK4 and cyclin D1
cycD1/CCND1↓,
mtDam↑, Lip-HNK caused apoptosis and death, which, in turn, led to the failure of mitochondrial membrane function
ROS↑, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
eff↓, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
Casp3↑, caspase-3 sectioned and the Bax protein level increased by Lip-HNK
BAX↑,
LC3II↑, LC3BII protein in the Lip-HNK-treated group was noticeably elevated
Beclin-1/ATG6↑, Beclin-1 (BECN), Atg7 proteins, and LC3BII were dramatically upregulated in the Lip-HNK-treated cells
ATG7↑,
p62↑, Lip-HNK treatment remarkably increased p62 expression, which was dose-dependent
eff↑, Lip-HNK treatment (20 mg/kg) drastically inhibited tumor growth. The combined treatment of Lip-HNK, Chloroquine , and Carboplatin showed more superior antitumor effects
ChemoSen↑, Lip-HNK alone or combined with chemotherapy (Carboplatin or Etoposide) causes significant regression of orthotopic xenografts
*toxicity↓, We also found that Lip-HNK did not damage the liver and kidney

2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2/KDR/Flk1↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2/PTGS2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP/DDIT3↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp/ABCB1↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

2863- HNK,    Honokiol induces paraptosis-like cell death through mitochondrial ROS-dependent endoplasmic reticulum stress in hepatocellular carcinoma Hep3B cells
- in-vitro, Liver, Hep3B
ER Stress↑, Honokiol also enhanced ER stress, increased cellular calcium ion (Ca2+) levels, and caused mitochondrial dysfunction
Ca+2↑,
mtDam↑,
PTEN↑, Honokiol upregulated the expression of mitophagy regulators such as PTEN-induced kinase 1 and Parkin in the mitochondria
PARK2↑,
Alix/AIP‑1↓, whereas the expression of apoptosis-linked gene 2-interacting protein X (Alix), involved in suppressing paraptosis, was downregulated.
ROS↑, honokiol-induced cytotoxicity was accompanied by excessive generation of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS).
mt-ROS↑,

2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
TumAuto↑,
Apoptosis↑,
*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
*neuroP↑, honokiol has neuroprotective effects.
*NF-kB↑, honokiol could reduce cytokine production and stimulate glial nuclear factor kappa B (NFκB) to eliminate the inflammatory response during cerebral ischemia-reperfusion activity
MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
BAX↑, BAX was increased, and the expression of Bcl-2 was suppressed in both honokiol-treated cells, indicating that honokiol induced apoptosis in the human glioma cell lines U87-MG and U251-MG.
Bcl-2↓,
antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells

2081- HNK,    Honokiol induces ferroptosis in colon cancer cells by regulating GPX4 activity
- in-vitro, Colon, RKO - in-vitro, Colon, HCT116 - in-vitro, Colon, SW48 - in-vitro, Colon, HT-29 - in-vitro, Colon, LS174T - in-vitro, Colon, HCT8 - in-vitro, Colon, SW480 - in-vivo, NA, NA
tumCV↓, HNK reduced the viability of CC cell lines by increasing ROS and Fe2+ levels
ROS↑, observations suggest that ROS production is a determining factor of HNK cytotoxicity. exact mechanism underlying the pro-oxidant activity of HNK is unclear in CC
Iron↑,
GPx4↓, HNK decreased the activity of Glutathione Peroxidase 4 (GPX4)
mtDam↑, intracellular mitochondria decreased, the membrane density increased, the mitochondrial ridge shrank or disappeared, and the bilayer membrane density increased.
Ferroptosis↑, results suggested that GPX4 may be the key molecule that regulates HNK-induced ferroptosis in CC cells
TumVol↓, tumor volumes and weights were significantly lower in the Lv-NC group than in the Lv-GPX4 group
TumW↓,

2080- HNK,    Honokiol Induces Ferroptosis by Upregulating HMOX1 in Acute Myeloid Leukemia Cells
- in-vitro, AML, THP1 - in-vitro, AML, U937 - in-vitro, AML, SK-HEP-1
tumCV↓, honokiol decreased the viability of the targeted AML cells
TumCCA↑, induced their cell cycle arrest at G0/G1 phase
Ferroptosis↑, Honokiol also triggers a noncanonical ferroptosis pathway in THP-1 and U-937 cells by upregulating the level of intracellular lipid peroxide and HMOX1 significantly.
lipid-P↑,
HO-1↑, HMOX1
GPx4∅, Honokiol elevated the expression of HMOX1 but did not inhibit the expression of GPX4

2079- HNK,    Honokiol Microemulsion Causes Stage-Dependent Toxicity Via Dual Roles in Oxidation-Reduction and Apoptosis through FoxO Signaling Pathway
- in-vitro, Nor, PC12
*toxicity↝, Our previous studies have already demonstrated that a high dose of the honokiol microemulsion (0.6 μg/mL) induces developmental toxicity in rats and zebrafish by inducing oxidative stress.
*ROS↓, In zebrafish, low doses of honokiol microemulsion (0.15, 0.21 μg/mL) significantly decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased the mRNA expression of bcl-2.
*ROS↑, In contrast, high dose (0.6 μg/mL) increased the levels of ROS and MDA, decreased activities and mRNA expression of superoxide dismutase (SOD) and catalase (CAT), and increased mRNA expression of bax, c-jnk, p53 and bim.
*Dose⇅, In rat pheochromocytoma cells (PC12 cells), low doses of the honokiol microemulsion (1, 5, 10 µM) exerted a protective effect against H2O2-induced oxidative damage while high doses (≥20 µM) induced oxidative stress, which further confirms the dual ef
*BioAv↑, highly lipophilic property of honokiol allows it to readily cross the blood-brain barrier and blood-cerebrospinal fluid barrier with high bioavailability.
*BioAv↓, However, this property also limits its clinical usage due to low oral bioavailability and difficulty in intravenous administration.
*ROS⇅, levels of ROS and MDA were significantly decreased at a concentration of 0.21 μg/mL and increased at a concentration of 0.6 μg/mL in both 24 and 96 hpf embryos
*SOD↓, The activity of SOD showed only a slight reduction at 20 µM but was significantly reduced at 40 and 80 μM
*toxicity↑, According to the human rat equivalent dosage conversion, the potential toxic dose in humans may be 320 µg/kg/d

2073- HNK,    Honokiol induces apoptosis and autophagy via the ROS/ERK1/2 signaling pathway in human osteosarcoma cells in vitro and in vivo
- in-vitro, OS, U2OS - in-vivo, NA, NA
TumCD↑, honokiol caused dose-dependent and time-dependent cell death in human osteosarcoma cells
TumAuto↑, death induced by honokiol were primarily autophagy and apoptosis.
Apoptosis↑,
TumCCA↑, honokiol induced G0/G1 phase arrest,
GRP78/BiP↑, elevated the levels of glucose-regulated protein (GRP)−78, an endoplasmic reticular stress (ERS)-associated protein
ROS↑, increased the production of intracellular reactive oxygen species (ROS)
eff↓, In contrast, reducing production of intracellular ROS using N-acetylcysteine, a scavenger of ROS, concurrently suppressed honokiol-induced cellular apoptosis, autophagy, and cell cycle arrest.
p‑ERK↑, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2.
selectivity↑, human fibroblasts showed strong resistance to HNK, the IC50 values for which were 118.9 and 71.5 μM
Ca+2↑, HNK increased intracellular Ca2+ in both HOS and U2OS cells
MMP↓, mitochondrial membrane potential (MMP) sharply decreased following HNK treatment
Casp3↑, HNK markedly activated caspase-3, caspase-9
Casp9↑,
cl‑PARP↑, led to PARP cleavage
Bcl-2↓, expression of Bcl-2, Bcl-xl, and survivin was found to be decreased
Bcl-xL↓,
survivin↓,
LC3B-II↑, HNK increased the level of LC3B-II and Atg5 in HOS and U2OS cells.
ATG5↑,
TumVol↓, HNK at doses of 40 mg/kg resulted in significant decrease in tumor volume and weight, after 7 days of drug administration
TumW↓,
ER Stress↑, ER stress can trigger ROS production through release of calcium


Showing Research Papers: 1 to 50 of 82
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 82

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

OTUB2↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 2,   Ferroptosis↑, 4,   GPx4↓, 1,   GPx4↑, 1,   GPx4∅, 1,   HO-1↓, 1,   HO-1↑, 1,   Iron↑, 1,   lipid-P↑, 1,   NRF2↑, 1,   PARK2↑, 1,   Prx3↑, 1,   ROS↑, 9,   mt-ROS↑, 2,   SIRT3↑, 5,   ac‑SOD2↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

Tf↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↓, 1,   MMP↓, 3,   mtDam↑, 5,   OCR↑, 2,   c-Raf↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

AKT1↓, 1,   AMPK↑, 2,   ATG7↑, 2,   cMyc↓, 1,   ECAR↓, 2,   GlucoseCon↓, 2,   Glycolysis↓, 2,   HK2↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   NADPH↓, 1,   PDK1 / PDPK1↓, 1,   SIRT1↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 5,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 12,   BAX↑, 3,   Bcl-2↓, 6,   Bcl-xL↓, 2,   Casp↑, 1,   Casp3↑, 4,   cl‑Casp3↑, 2,   Casp9↑, 4,   cFLIP↓, 1,   Cyt‑c↑, 2,   DR5↑, 1,   Ferroptosis↑, 4,   cl‑GSDME↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↑, 1,   MDM2↓, 1,   p27/CDKN1B↑, 1,   Pyro↑, 1,   survivin↓, 4,   TumCD↓, 1,   TumCD↑, 1,   YAP/TEAD↓, 2,  

Kinase & Signal Transduction(tgid=6) ⓘ

EF-1α↓, 1,   HER2/EBBR2↓, 1,   p70S6↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

cJun↑, 1,   EZH2↓, 1,   H3↑, 1,   H4↑, 1,   HATs↑, 1,   tumCV↓, 5,  

Protein Folding & ER Stress(tgid=8) ⓘ

cl‑CHOP/DDIT3↑, 1,   ER Stress↑, 3,   GRP78/BiP↑, 2,   HSP27↓, 1,   HSP90↓, 2,  

Autophagy & Lysosomes(tgid=9) ⓘ

ATG5↑, 2,   Beclin-1/ATG6↑, 1,   LC3B-II↑, 1,   LC3II↑, 2,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair(tgid=10) ⓘ

CYP1B1↓, 1,   P53↑, 2,   cl‑PARP↑, 4,   PCNA↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK2↓, 3,   CDK4↓, 5,   cycD1/CCND1↓, 6,   cycE/CCNE↓, 1,   P21?, 1,   P21↑, 3,   p‑RB1↓, 1,   TumCCA↓, 1,   TumCCA↑, 7,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CD133↓, 1,   CD44↓, 1,   CSCs↓, 4,   EMT↓, 5,   p‑ERK↑, 1,   FOXM1↓, 1,   Gli1↓, 1,   HDAC↓, 1,   HDAC1↓, 1,   HH↓, 1,   miR-34a↑, 1,   mTOR↓, 3,   p‑mTOR↓, 2,   mTORC1↓, 1,   Nanog↓, 1,   Nestin↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   OCT4↓, 1,   PI3K↓, 7,   PTCH1↓, 1,   PTEN↑, 2,   RAS↓, 1,   Shh↓, 1,   SOX2↓, 1,   STAT3↓, 2,   p‑STAT3↓, 1,   mt-STAT3↓, 1,   TAZ↓, 1,   TumCG↓, 5,   Wnt↓, 2,  

Migration(tgid=13) ⓘ

Alix/AIP‑1↓, 1,   Ca+2↑, 3,   E-cadherin↑, 1,   MMP2↓, 2,   MMP9↓, 3,   MMPs↓, 1,   N-cadherin↓, 1,   Rho↑, 1,   ROCK1↑, 1,   Slug↓, 1,   Snail↓, 2,   SOX4↓, 1,   TumCI↓, 5,   TumCMig↓, 6,   TumCP↓, 10,   TumCP↑, 1,   TumMeta↓, 2,   Twist↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,   β-catenin/ZEB1↑, 2,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 1,   EGFR↓, 3,   Hif1a↓, 7,   VEGF↓, 2,   VEGFR2/KDR/Flk1↓, 1,  

Barriers & Transport(tgid=15) ⓘ

GLUT1↓, 1,   P-gp/ABCB1↓, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 3,   IKKα↓, 1,   IL6↓, 1,   Imm↝, 1,   Inflam↓, 2,   NF-kB↓, 5,   p65↓, 1,   PGE2↓, 1,   TNF-α↓, 1,   TNF-α↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

CDK6↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 5,   BioAv↑, 2,   BioAv↝, 2,   ChemoSen↑, 9,   Dose↝, 4,   eff↓, 3,   eff↑, 10,   Half-Life↓, 1,   Half-Life↝, 2,   RadioS↑, 2,   selectivity↑, 6,  

Clinical Biomarkers(tgid=22) ⓘ

BMPs↑, 1,   EGFR↓, 3,   EZH2↓, 1,   FOXM1↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 5,   chemoP↑, 2,   neuroP↑, 1,   OS↑, 2,   TumVol↓, 2,   TumW↓, 2,  
Total Targets: 190

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

QPCT/QC↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 5,   GSH↑, 1,   Keap1↑, 1,   NRF2↑, 1,   OXPHOS↑, 1,   ROS↓, 13,   ROS↑, 1,   ROS⇅, 1,   SIRT3↑, 5,   SOD↓, 1,   SOD2↑, 2,   Trx↑, 1,   TrxR1↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ATP↑, 1,   mitResp↑, 2,   MMP↑, 3,   PGC-1α↑, 3,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   CREB↑, 1,   Glycolysis↑, 1,   LDH↓, 1,   PPARα↑, 1,   PPARγ↑, 4,  

Cell Death(tgid=5) ⓘ

Apoptosis↓, 2,   Casp3↓, 2,  

Transcription & Epigenetics(tgid=7) ⓘ

Ach↑, 1,   AntiThr↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

ERK↓, 1,   GSK‐3β↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,   Ca+2↓, 1,   Rho↓, 1,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

IL1?, 1,   IL1β↓, 1,   IL6?, 1,   Inflam↓, 6,   NF-kB↓, 1,   NF-kB↑, 1,   TNF-α↓, 3,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 1,   BDNF↑, 4,   TrkB↑, 1,  

Protein Aggregation(tgid=19) ⓘ

Aβ↓, 2,   BACE/β-secretase↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 2,   Dose⇅, 1,   Half-Life↝, 1,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   IL6?, 1,   LDH↓, 1,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 1,   cardioP↑, 5,   cognitive↑, 1,   hepatoP↑, 2,   memory↑, 2,   Mood↑, 1,   motorD↑, 1,   neuroP↑, 5,   radioP↑, 1,   toxicity↓, 3,   toxicity↑, 1,   toxicity↝, 1,   toxicity∅, 1,  
Total Targets: 67

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

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