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↓, 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


Scientific Papers found: Click to Expand⟱
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
"highlight2" >*SIRT3↑, We have recently identified honokiol (HKL) as an activator of SIRT3
"highlight2" >chemoP↑, HKL-mediated activation of SIRT3 also protects the heart from doxorubicin-induced cardiac damage without compromising the tumor killing potential of doxorubicin.
"highlight2" >*cardioP↑, mice that received doxorubicin plus HKL showed preserved cardiac function, compared to doxorubicin and vehicle treated mice
"highlight2" >mtDam↑, HKL-mediated activation of SIRT3 prevented Doxorubicin induced ROS production, mitochondrial damage and cell death in rat neonatal cardiomyocytes
"highlight2" >ROS↑,
"highlight2" >*ROS↓, We found that cells treated with HKL suppressed doxorubicin-induced ROS levels
"highlight2" >*MMP↑, HKL preserves mitochondrial membrane potential.

2876- HNK,    Honokiol from Magnolia spp. induces G1 arrest via disruption of EGFR stability through repressing HDAC6 deacetylated Hsp90 function in lung cancer cells
- in-vitro, Lung, A549 - in-vitro, Lung, H23 - in-vitro, Lung, HCC827
"highlight2" >EGFR↓, Honokiol down-regulated EGFR expression was through ubiquitin/proteasome degradation.
"highlight2" >HSP90↓, Honokiol repressed Hsp90 and EGFR association and followed by EGFR degradation.

2877- HNK,    Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer
- in-vitro, GC, AGS
"highlight2" >HDAC3↓, Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPβ signaling,
"highlight2" >NF-kB↓,
"highlight2" >CEBPB↓,
"highlight2" >ER Stress↑, Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/β-catenin activity
"highlight2" >EMT↓,
"highlight2" >Wnt↓,
"highlight2" >β-catenin/ZEB1↓,

2878- HNK,    Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6-mediated matrix metalloproteinase 9
- in-vitro, Lung, H1299
"highlight2" >TumCMig↓, migration and invasion ability of H1299 lung cancer was suppressed by noncytotoxic concentrations of honokiol treatment.
"highlight2" >TumCI↓,
"highlight2" >MMP9↓, proteolytic activity of MMP-9, rather than MMP-2, was inhibited in honokiol-treated H1299 cells.
"highlight2" >α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl-α-tubulin, was accumulated after honokiol incubation
"highlight2" >HDAC6↓, suppression of migration and invasion activities by honokiol was through inhibiting HDAC6-mediated Hsp90/MMP-9 interaction and followed by MMP-9 degradation in lung cancer.
"highlight2" >HSP90↓, Honokiol-suppressed MMP-9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway

2879- HNK,    Honokiol Inhibits Lung Tumorigenesis through Inhibition of Mitochondrial Function
- in-vitro, Lung, H226 - in-vivo, NA, NA
"highlight2" >tumCV↓, honokiol significantly reduced the percentage of bronchial that exhibit abnormal lung SCC histology from 24.4% bronchial in control to 11.0% bronchial in honokiol treated group (p= 0.01) while protecting normal bronchial histology (present in 20.5%
"highlight2" >selectivity↑,
"highlight2" >TumCP↓, In vitro studies revealed that honokiol inhibited lung SCC cells proliferation, arrested cells at the G1/S cell cycle checkpoint, while also leading to increased apoptosis.
"highlight2" >TumCCA↑,
"highlight2" >Apoptosis↑,
"highlight2" >mt-ROS↑, interfering with mitochondrial respiration is a novel mechanism by which honokiol increased generation of reactive oxygen species (ROS) in the mitochondria, : mitochondrial ROS generation
"highlight2" >Casp3↑, cells treated with honokiol showed a significant increase in caspase 3/7 activity, which occurred in dose- and time-dependent manners
"highlight2" >Casp7↑,
"highlight2" >OCR↓, Honokiol caused a fast and concentration-dependent decrease in basal oxygen consumption rate (OCR) in both cell lines
"highlight2" >Cyt‑c↑, cytochrome c release was increased in honokil treated mouse lung SCC tissue
"highlight2" >ATP↓, found a dramatic decrease in cellular ATP content
"highlight2" >mitResp↓, Honokiol inhibits mitochondrial respiration and decreases ATP levels in H226 and H520 cells, which may elevate AMP and the intracellular AMP/ATP ratio, leading to activation of the AMPK
"highlight2" >AMP↑,
"highlight2" >AMPK↑,

2880- HNK,    Honokiol inhibits breast cancer cell metastasis by blocking EMT through modulation of Snail/Slug protein translation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, 4T1 - in-vivo, NA, NA
"highlight2" >tumCV↓, HNK (10−70 μmol/L) dose-dependently inhibited the viability of human mammary epithelial tumor cell lines MCF7, MDA-MB-231, and mouse mammary tumor cell line 4T1
"highlight2" >E-cadherin↑, dose-dependently upregulated the epithelial marker E-cadherin and downregulated the mesenchymal markers such as Snail, Slug, and vimentin at the protein level in breast cancer cells
"highlight2" >Snail↓,
"highlight2" >Slug↓,
"highlight2" >Vim↓,
"highlight2" >TumMeta↓, HNK inhibits the in vivo metastasis of breast cancer cells
"highlight2" >p‑eIF2α↑, increased eIF2α phosphorylation revealed that HNK might reduce protein translation.

2881- HNK,    Honokiol Suppressed Pancreatic Cancer Progression via miR-101/Mcl-1 Axis
- in-vitro, PC, PANC1
"highlight2" >tumCV↓, Honokiol concentration-dependently suppressed pancreatic cancer cell viability.
"highlight2" >Casp3↑, honokiol increased the caspase-3 activity and cell apoptotic rates, induced cell cycle arrest at G0/G1 phase, and inhibited cell invasion in pancreatic cancer.
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑,
"highlight2" >TumCI↓,
"highlight2" >Mcl-1↓, up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues.
"highlight2" >EMT↓, Recent studies reported honokiol inhibits cancer metastasis by blocking EMT through modulation of Snail/Slug protein translation

2882- HNK,    Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling
- in-vitro, PC, PANC1
"highlight2" >TumCI↓, HNK can inhibit the invasion and migration of pancreatic cancer cells.
"highlight2" >TumCMig↓,
"highlight2" >p‑SMAD2↓, partially mediated by inhibition of SMAD2/3 phosphorylation.
"highlight2" >p‑SMAD3↓,
"highlight2" >EMT↓, HNK Inhibits Pancreatic Cancer Malignant Behaviors and EMT
"highlight2" >N-cadherin↓, expression of N-cadherin and Vimentin was gradually downregulated, while HNK promoted the expression of E-cadherin in PANC-1
"highlight2" >Vim↓,
"highlight2" >E-cadherin↑,
"highlight2" >Snail↓, HNK can inhibit breast cancer cell metastasis by blocking EMT through downregulating Snail/Slug protein translation
"highlight2" >Slug↓,
"highlight2" >Rho↓, Honokiol inhibits the migration of renal cell carcinoma through activation of the RhoA/ROCK/MLC signaling pathway
"highlight2" >ROCK1↓,

2883- HNK,    Honokiol targets mitochondria to halt cancer progression and metastasis
- Review, Var, NA
"highlight2" >ChemoSen↑, Combination of HNK with many traditional chemotherapeutic drugs as well as radiation sensitizes cancer cells to apoptotic death
"highlight2" >BBB↓, HNK is also capable of crossing the BBB
"highlight2" >Ca+2↑, HNK promotes human glioblastoma cancer cell apoptosis via regulation of Ca(2+) channels
"highlight2" >Cyt‑c↑, release of mitochondrial cytochrome c and activation of caspase-3
"highlight2" >Casp3↑,
"highlight2" >chemoP↑, potent chemopreventive agent against lung SCC development in a carcinogen-induced lung SCC murine model
"highlight2" >OCR↓, HNK treatment results in a decreased oxygen consumption rate (OCR) in whole intact cells, rapidly, and persistently inhibiting mitochondrial respiration, which leads to the induction of apoptosis
"highlight2" >mitResp↓,
"highlight2" >Apoptosis↑,
"highlight2" >RadioS↑, Honokiol as a chemo- and radiosensitizer
"highlight2" >NF-kB↓, HNK as an anticancer drug is its potential to inhibit multiple important survival pathways, such as NF-B and Akt
"highlight2" >Akt↓,
"highlight2" >TNF-α↓, by inhibiting TNF-induced nerve growth factor IB expression in breast cancer cells
"highlight2" >PGE2↓, reduced prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF) secretion levels
"highlight2" >VEGF↓,
"highlight2" >NO↝, HNK inhibits cancer cell migration by targeting nitric oxide and cyclooxygenase-2 or Ras GTPase-activating-like protein (IQGAP1) [
"highlight2" >COX2↓,
"highlight2" >RAS↓,
"highlight2" >EMT↓, HNK can reverse the epithelial-mesenchymal-transition (EMT) process, which is a key step during embryogenesis, cancer invasion, and metastasis,
"highlight2" >Snail↓, HNK reduced the expression levels of Snail, N-cadherin and -catenin, which are mesenchymal markers, but increased E-cadherin,
"highlight2" >N-cadherin↓,
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >E-cadherin↑,
"highlight2" >ER Stress↑, induction of ER stress
"highlight2" >p‑STAT3↓, HNK inhibited STAT3 phosphorylation
"highlight2" >EGFR↓, inhibiting EGFR phosphorylation and its downstream signaling pathways such as the mTOR signaling pathway
"highlight2" >mTOR↓,
"highlight2" >mt-ROS↑, We demonstrated that HNK treatment suppresses mitochondrial respiration and increases generation of ROS in the mitochondria, leading to the induction of apoptosis in lung cancer cells
"highlight2" >PI3K↓, inhibition of PI3K/Akt/ mTOR, EMT, and Wnt signaling pathways.
"highlight2" >Wnt↓,

2884- HNK,    Honokiol inhibits EMT-mediated motility and migration of human non-small cell lung cancer cells in vitro by targeting c-FLIP
- in-vitro, Lung, A549 - in-vitro, Lung, H460
"highlight2" >EMT↓, HNK inhibits EMT-mediated motility and migration of human NSCLC cells in vitro by targeting c-FLIP,
"highlight2" >cFLIP↓,
"highlight2" >N-cadherin↓, increased c-FLIP, N-cadherin (a mesenchymal marker), snail (a transcriptional modulator) and p-Smad2/3 expression, and decreased IκB levels in the cells; these changes were abrogated by co-treatment with HNK (30 μmol/L)
"highlight2" >Snail↓,
"highlight2" >p‑SMAD2↓,
"highlight2" >p‑SMAD3↓,
"highlight2" >IKKα↑,
"highlight2" >TumCMig↓, HNK inhibits the migration of A549 and H460 cells induced by TNF-α+TGF-β1
"highlight2" >NA↑,

2885- HNK,    Honokiol: a novel natural agent for cancer prevention and therapy
"highlight2" >NF-kB↓, Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR)
"highlight2" >STAT3↓,
"highlight2" >EGFR↓,
"highlight2" >mTOR↓,
"highlight2" >BioAv↝, honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials
"highlight2" >Inflam↓, inflammation, proliferation, angiogenesis, invasion and metastasis.
"highlight2" >TumCP↓,
"highlight2" >angioG↓,
"highlight2" >TumCI↓,
"highlight2" >TumMeta↓,
"highlight2" >cSrc↓, STAT3 inhibition by honokiol has also been correlated with the repression of upstream protein tyrosine kinases c-Src, JAK1 and JAK2
"highlight2" >JAK1↓,
"highlight2" >JAK2↓,
"highlight2" >ERK↓, by inhibiting ERK and Akt pathways (31) or by upregulation of PTEN
"highlight2" >Akt↓,
"highlight2" >PTEN↑,
"highlight2" >ChemoSen↑, Chemopreventive/ chemotherapeutic effects of honokiol in various malignancies: preclinical studies
"highlight2" >chemoP↑,
"highlight2" >COX2↓, honokiol was found to inhibit UVB-induced expression of cyclooxygenase-2, prostaglandin E2, proliferating cell nuclear antigen and pro-inflammatory cytokines, such as TNF-α, interleukin (IL)-1β and IL-6 in the skin
"highlight2" >PGE2↓,
"highlight2" >TNF-α↓,
"highlight2" >IL1β↓,
"highlight2" >IL6↓,
"highlight2" >Casp3↑, release of caspases-3, -8 and -9as well as poly (ADP-ribose) polymerase (PARP) cleavage and p53 activation upon honokiol treatment that led to DNA fragmentation
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >DNAdam↑,
"highlight2" >Cyt‑c↑, translocation of cytochrome c to cytosol in human melanoma cell lines
"highlight2" >RadioS↑, liposomal honokiol for 24 h showed a higher radiation enhancement ratio (~ two-fold) as compared to the radiation alone,
"highlight2" >RAS↓, Honokiol also caused suppression of Ras activation
"highlight2" >BBB↑, honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth
"highlight2" >BioAv↓, Due to the concerns about poor aqueous solubility, liposomal formulations of honokiol have been developed and tested for their pharmacokinetics
"highlight2" >Half-Life↝, In another comparative study, plasma honokiol concentrations was maintained above 30 and 10 μg/mL for 24 and 48 hours, respectively, in liposomal honokiol-treated mice, whereas it fell quickly (less than 5 μg/mL) by 12 hours in free honokiol-treated
"highlight2" >Half-Life↝, free honokiol has poor GIT absorption, bio-transformed in liver to mono-glucuronide honokiol and sulphated mono-hydroxyhonokiol, ~ 50% is secreted in bile, ~ 60-65% plasma protein bound with elimination half life of (t1/2) of 49.05 – 56.24 minutes.
"highlight2" >toxicity↓, These studies suggest that honokiol either alone or as a part of magnolia bark extract does not induce toxicity in animal models and thus could be clinically safe

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
"highlight2" >eff↑, Lipo-HNK, with enhanced solubility and bioavailability, demonstrated potent cytotoxicity against NSCLC cell lines.
"highlight2" >BioAv↑,
"highlight2" >eff↑, Lipo-HNK exhibited synergistic anti-cancer effects when combined with anti-PD-1 therapy
"highlight2" >PI3K↓, inhibiting the PI3K/Akt
"highlight2" >Akt↓,

2887- HNK,    Honokiol Restores Microglial Phagocytosis by Reversing Metabolic Reprogramming
- in-vitro, AD, BV2
"highlight2" >*Glycolysis↑, switch from oxidative phosphorylation to anaerobic glycolysis and enhancing ATP production.
"highlight2" >*ATP↑,
"highlight2" >*ROS↓, honokiol reduced mitochondrial reactive oxygen species production and elevated mitochondrial membrane potential.
"highlight2" >*MMP↑,
"highlight2" >*OXPHOS↑, Honokiol enhanced ATP production by promoting mitochondrial OXPHOS in BV2 cell
"highlight2" >*PPARα↑, Therefore, we argue that honokiol increases the expression of PPAR and PGC1, thus regulating a metabolic switch from glycolysis to OXPHOS
"highlight2" >*PGC-1α↑,

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
"highlight2" >PI3K↓, decrease PI3K/mTOR pathway mediated immunoresistance of glioma, breast and prostate cancer cell lines, without affecting critical pro-inflammatory T cell functions
"highlight2" >mTOR↓,
"highlight2" >Inflam↓, Honokiol has anti-inflammatory properties in T cells

2875- HNK,    Inhibition of class I histone deacetylases in non-small cell lung cancer by honokiol leads to suppression of cancer cell growth and induction of cell death in vitro and in vivo
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, SCC, H226
"highlight2" >HDAC↓, Treatment of NSCLC cells (A549, H1299, H460 and H226) with honokiol (20, 40 and 60 µM) inhibited histone deacetylase (HDAC) activity, reduced the levels of class I HDAC proteins and enhanced histone acetyltransferase activity in a dose-dependent man
"highlight2" >tumCV↓, These effects of honokiol were associated with a significant reduction in the viability of NSCLC cells
"highlight2" >TumCCA↑, Treatment of A549 and H1299 cells with honokiol resulted in an increase in G1 phase arrest, and a decrease in the levels of cyclin D1, D2 and cyclin dependent kinases.
"highlight2" >cycD1↓,
"highlight2" >ac‑H3↑, Honokiol increases the levels of acetylated histone H3 and H4 in NSCLC cells
"highlight2" >ac‑H4↑,
"highlight2" >selectivity↑, Honokiol inhibits cell growth or viability of human NSCLC cells but not normal human bronchial epithelial cells
"highlight2" >CDK2↓, Similarly, a marked reduction in the expression of CDK2, CDK4 and CDK6 proteins was observed
"highlight2" >CDK4↓,

2890- HNK,    SIRT3 activation promotes enteric neurons survival and differentiation
"highlight2" >*SIRT3↑, Honokiol, a naturally occurring compound, is an activator of Sirtuin-3 (SIRT3) that has antioxidant activity.
"highlight2" >*antiOx↑,
"highlight2" >*neuroP↑, Our data supports a neuroprotective effect of honokiol and its derivative

2891- HNK,    Honokiol, an Active Compound of Magnolia Plant, Inhibits Growth, and Progression of Cancers of Different Organs
- Review, Var, NA
"highlight2" >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.
"highlight2" >Inflam↓,
"highlight2" >antiOx↑,
"highlight2" >selectivity↑,
"highlight2" >*toxicity↓,
"highlight2" >cycD1↓, honokiol resulted in inhibition of UVB-induced expression levels of cyclins (cyclins D1, D2, and E) and CDKs in skin tumors
"highlight2" >cycE↓,
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >TumMeta↓, Honokiol Inhibits Metastatic Potential of Melanoma Cells
"highlight2" >NADPH↓, Honokiol not only reduces the NADPH oxidase activity
"highlight2" >MMP2↓, honokiol treatment reduces the expression of MMP-2 and MMP-9
"highlight2" >MMP9↓,
"highlight2" >p‑mTOR↓, honokiol caused significant downregulation of mTOR phosphorylation
"highlight2" >EGFR↓, honokiol decreases the expression levels of total EGFR
"highlight2" >EMT↓, honokiol effectively inhibits EMT in breast cancer cells
"highlight2" >SIRT1↑, onokiol increases the expressions of SIRT1 and SIRT3,
"highlight2" >SIRT3↑,
"highlight2" >EZH2↓, depletion of EZH2 by honokiol treatment inhibited cell proliferation
"highlight2" >Snail↓, significantly down regulates Snail, vimentin, N-cadherin expression, and upregulates cytokeratin-18 and E-cadherin expression
"highlight2" >Vim↓,
"highlight2" >N-cadherin↓,
"highlight2" >E-cadherin↑,
"highlight2" >COX2↓, honokiol as an inhibitor of COX-2 expression
"highlight2" >NF-kB↓, inhibited transcriptional activity of NF-jB,
"highlight2" >*ROS↓, Inhibition of UVR-induced inflammatory mediators as well as ROS by honokiol treatment contributes to the prevention of UVR-induced skin tumor development
"highlight2" >Ca+2↑, excessive influx of cytosolic calcium ion into the mitochondria triggers dysfunction of the mitochon- drial membrane permeabilization with mitochondrial ROS induction
"highlight2" >ROS↑,

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
"highlight2" >TumCCA↑, Honokiol was shown to induce G1 arrest and apoptosis to inhibit the growth of KRAS mutant lung cancer cells
"highlight2" >Apoptosis↑,
"highlight2" >SIRT3↑, we also discovered that Sirt3 was significantly up-regulated in honokiol treated KRAS mutant lung cancer cells,
"highlight2" >Hif1a↓, leading to destabilization of its target gene Hif-1α, (accompanied by a reduction of Hif-1a expression)
"highlight2" >selectivity↑, but it showed low toxicity to two normal lung cells (CCD19-Lu and BEAS-2B)
"highlight2" >p‑mTOR↓, honokiol suppressed mTOR phosphorylation, leading to inhibition of P70S6K kinase activity,
"highlight2" >p70S6↓,

2893- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
"highlight2" >*mitResp↑, Oxygen consumption in freshly isolated mitochondria from mice treated with Honokiol showed enhanced mitochondrial respiration.
"highlight2" >*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat
"highlight2" >*cardioP↑, Honokiol alleviated Dox-cardiotoxicity with improved cardiac function and reduced cardiomyocyte apoptosis
"highlight2" >*SIRT3↑, recent study reported that Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial SIRT3
"highlight2" >*ROS↓, Honokiol treatment depressed total ROS levels, which illustrated by the less pronounced decreased ratio of GSH/GSSG in mice
"highlight2" >*GSH↑,
"highlight2" >*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice

2894- HNK,    Pharmacological features, health benefits and clinical implications of honokiol
- Review, Var, NA - Review, AD, NA
"highlight2" >*BioAv↓, HNK showed poor aqueous solubility due to phenolic hydroxyl groups forming intramolecular hydrogen bonds and poor solubility in water (
"highlight2" >*neuroP↑, HNK has the accessibility to reach the neuronal tissue by crossing the BBB and showing neuroprotective effects
"highlight2" >*BBB↑,
"highlight2" >*ROS↓, fig 2
"highlight2" >*Keap1↑,
"highlight2" >*NRF2↑,
"highlight2" >*Casp3↓,
"highlight2" >*SIRT3↑,
"highlight2" >*Rho↓,
"highlight2" >*ERK↓,
"highlight2" >*NF-kB↓,
"highlight2" >angioG↓,
"highlight2" >RAS↓,
"highlight2" >PI3K↓,
"highlight2" >Akt↓,
"highlight2" >mTOR↓,
"highlight2" >*memory↑, oral administration of HNK (1 mg/kg) in senescence-accelerated mice prevents age-related memory and learning deficits
"highlight2" >*Aβ↓, in Alzheimer’s disease, HNK significantly reduces neurotoxicity of aggregated Ab
"highlight2" >*PPARγ↑, Furthermore, the expression of PPARc and PGC1a was increased by HNK, suggesting its beneficial impact on energy metabolism
"highlight2" >*PGC-1α↑,
"highlight2" >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
"highlight2" >Hif1a↓, HNK has anti-oxidative properties and can downregulate the HIF-1a protein, inhibiting hypoxia- related signaling pathways
"highlight2" >VEGF↓, renal cancer, via decreasing the vascular endothelial growth factor (VEGF) and heme-oxygenase-1 (HO-1)
"highlight2" >HO-1↓,
"highlight2" >Foxm1↓, HNK interaction with the FOXM1 oncogenic transcription factor inhibits cancer cells
"highlight2" >p27↑, HNK treatment upregulates the expression of CDK inhibitor p27 and p21, whereas it downregulates the expression of CDK2/4/6 and cyclin D1/2
"highlight2" >P21↑,
"highlight2" >CDK2↓,
"highlight2" >CDK4↓,
"highlight2" >CDK6↓,
"highlight2" >cycD1↓,
"highlight2" >Twist↓, HNK averted the invasion of urinary bladder cancer cells by downregulating the steroid receptor coactivator, Twist1 and Matrix metalloproteinase-2
"highlight2" >MMP2↓,
"highlight2" >Rho↑, By activating the RhoA, ROCK and MLC signaling, HNK inhibits the migration of highly metastatic renal cell carcinoma
"highlight2" >ROCK1↑,
"highlight2" >TumCMig↓,
"highlight2" >cFLIP↓, HNK can be used to suppress c-FLIP, the apoptosis inhibitor.
"highlight2" >BMPs↑, HNK treatment increases the expression of BMP7 protein
"highlight2" >OCR↑, HNK might increase the oxygen consumption rate while decreasing the extracellular acidification rate in breast cancer cells.
"highlight2" >ECAR↓,
"highlight2" >*AntiAg↑, It also suppresses the platelet aggregation
"highlight2" >*cardioP↑, HNK is an attractive cardioprotective agent because of its strong antioxidative properties
"highlight2" >*antiOx↑,
"highlight2" >*ROS↓, HNK treatment reduced cellular ROS production and decreased mitochondrial damage in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation
"highlight2" >P-gp↓, 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

2895- HNK,    Mitochondria-Targeted Honokiol Confers a Striking Inhibitory Effect on Lung Cancer via Inhibiting Complex I Activity
- in-vitro, Lung, PC9
"highlight2" >eff↑, Mito-HNK is >100-fold more potent than HNK in inhibiting cell proliferation
"highlight2" >TumCP↓,
"highlight2" >mt-ROS↑, inhibiting mitochondrial complex ǀ, stimulating reactive oxygen species generation, oxidizing mitochondrial peroxiredoxin-3, and suppressing the phosphorylation of mitoSTAT3
"highlight2" >Prx3↑,
"highlight2" >mt-STAT3↓,
"highlight2" >*toxicity∅, Mito-HNK showed no toxicity and targets the metabolic vulnerabilities of primary and metastatic lung cancers.
"highlight2" >selectivity↑,
"highlight2" >ChemoSen↑, combination with standard chemotherapeutics.

2896- HNK,    Honokiol inhibits hypoxia-inducible factor-1 pathway
- in-vivo, Colon, CT26
"highlight2" >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.
"highlight2" >RadioS↑, The animal experiment indicates that honokiol improves the therapeutic efficacy of radiation

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
"highlight2" >TumCP↓, Honokiol Inhibits Cell Proliferation in Both A549 Cells and PC-9 Cells
"highlight2" >Apoptosis↑, Honokiol Induces Apoptosis in PC-9 Cells
"highlight2" >EGFR↓, Honokiol Suppresses Lyn Kinase and EGFR Signaling Pathway in PC-9 Cells
"highlight2" >PI3K↓, led to a reduction of EGFR/PI3K/AKT and STAT3, and their phosphorylation status.
"highlight2" >Akt↓,
"highlight2" >STAT3↓,
"highlight2" >TumCI↓, honokiol inhibits PC-9 cell proliferation, invasion and induces apoptosis through targeting Lyn kinase and Lyn-mediated EGFR signaling pathway.
"highlight2" >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.
"highlight2" >NF-kB↓,
"highlight2" >VEGF↓,
"highlight2" >MMP9↓,
"highlight2" >COX2↓,

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
"highlight2" >TumCP↓, Honokiol suppressed cell proliferation via increasing cell apoptosis, invasion, and migration with dose dependence.
"highlight2" >Apoptosis↑,
"highlight2" >TumCI↓,
"highlight2" >TumCMig↓,
"highlight2" >HER2/EBBR2↓, HER2 protein expression was significantly depressed in honokiol-treated groups
"highlight2" >TumCCA↑, results show that Hon kept the cell cycle in G1 phase, which might be the cause of the cell apoptosis rate increase.
"highlight2" >PI3K↓, PI3K, AKT, and MMP-9 protein and mRNA expression of Hon-treated groups were significantly suppressed
"highlight2" >Akt↓,
"highlight2" >MMP9↓,
"highlight2" >P21↑, increase P21 protein and gene expression

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
"highlight2" >*memory↑, Honokiol attenuated surgery-induced memory loss and neuronal apoptosis, decreased neuroinflammatory response, and ameliorated oxidative damage in hippocampus.
"highlight2" >*Inflam↓,
"highlight2" >*ROS↓,
"highlight2" >neuroP↑,
"highlight2" >SIRT3↑, HNK increased SIRT3 expression and thus decreased the acetylation of superoxide dismutase 2 (SOD2).
"highlight2" >ac‑SOD2↓,

2900- HNK,    The Role and Therapeutic Perspectives of Sirtuin 3 in Cancer Metabolism Reprogramming, Metastasis, and Chemoresistance
- Review, Var, NA
"highlight2" >SIRT3↑, Honokiol blocks the growth of lung cancer cells by activating SIRT3 to inhibit HIF-1α expression
"highlight2" >Hif1a↓,
"highlight2" >ChemoSen↑, and also be used as adjuvant chemotherapy to prevent doxorubicin-induced cardiotoxicity in tumors transplanted mice
"highlight2" >chemoP↑,

2901- HNK,  doxoR,    Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts
- in-vivo, Nor, NA
"highlight2" >*mitResp↑, mice treated with Honokiol showed enhanced mitochondrial respiration
"highlight2" >*PPARγ↑, Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat cardiomyocytes
"highlight2" >*Inflam↓, Honokiol repressed cardiac inflammatory responses and oxidative stress in mice subjected to Dox treatment.
"highlight2" >*ROS↓,
"highlight2" >*cardioP↑, We conclude that Honokiol protects the heart from Dox-cardiotoxicity
"highlight2" >*SOD2↑, Both SOD2 and CD36 were upregulated in the heart of Honokiol treated mice
"highlight2" >*LDH↓, Furthermore, Honokiol treatment reduced the Dox-induced elevation of lactate dehydrogenase (LDH) activity (Fig. 6D) in mice subjected to acute Dox treatment.

2902- HNK,  Rad,    Honokiol Mitigates Ionizing Radiation-Induced Injury by Maintaining the Redox Balance of the TrxR/Trx System
- in-vitro, Nor, BEAS-2B
"highlight2" >*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
"highlight2" >*Trx↑,
"highlight2" >*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
"highlight2" >*ROS↓, Compared to the IR group, there was a significant decrease in the ROS levels of the HKL+IR treated group

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
"highlight2" >tumCV↓, HNK reduced the viability of CC cell lines by increasing ROS and Fe2+ levels
"highlight2" >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
"highlight2" >Iron↑,
"highlight2" >GPx4↓, HNK decreased the activity of Glutathione Peroxidase 4 (GPX4)
"highlight2" >mtDam↑, intracellular mitochondria decreased, the membrane density increased, the mitochondrial ridge shrank or disappeared, and the bilayer membrane density increased.
"highlight2" >Ferroptosis↑, results suggested that GPX4 may be the key molecule that regulates HNK-induced ferroptosis in CC cells
"highlight2" >TumVol↓, tumor volumes and weights were significantly lower in the Lv-NC group than in the Lv-GPX4 group
"highlight2" >TumW↓,

1004- HNK,  RAPA,    Honokiol downregulates PD-L1 expression and enhances antitumor effects of mTOR inhibitors in renal cancer cells
- in-vitro, RCC, NA
"highlight2" >Apoptosis↑, HNK is more potent than RAPA, both HNK and RAPA inhibited the proliferation of renal cancer cells and promoted apoptosis
"highlight2" >TumCCA↑, G1 phase cell cycle arrest
"highlight2" >ROS↑, HNK and RAPA significantly increased ROS generation in these cells and it was much higher in the HNK and RAPA combinatorial treatment.
"highlight2" >PD-L1↓, HNK, but not RAPA, significantly decreased the expression of PD-L1
"highlight2" >IFN-γ↓, HNK can also downmodulate IFN-γ-induced PD-L1expression

1021- HNK,    Honokiol suppress the PD-L1 expression to improve anti-tumor immunity in lung cancer
- in-vivo, Lung, NA
"highlight2" >PD-L1↓, in cells with high PD-L1 expression
"highlight2" >T-Cell↑, facilitates T cell killing of tumor cells
"highlight2" >CD4+↑,
"highlight2" >CD8+↑,
"highlight2" >TumCG↓, mice

1087- HNK,    Honokiol Inhibits Non-Small Cell Lung Cancer Cell Migration by Targeting PGE2-Mediated Activation of β-Catenin Signaling
- in-vitro, Lung, A549 - in-vitro, Lung, H1299 - in-vitro, Lung, H460 - in-vitro, Lung, H226
"highlight2" >TumCMig↓,
"highlight2" >COX2↓,
"highlight2" >PGE2↓,
"highlight2" >NF-kB↓,
"highlight2" >p65↓,
"highlight2" >β-catenin/ZEB1↓,
"highlight2" >MMP2↓,
"highlight2" >MMP9↓,

1119- HNK,    Honokiol inhibits epithelial—mesenchymal transition in breast cancer cells by targeting signal transducer and activator of transcription 3/Zeb1/E‐cadherin axis
- vitro+vivo, BC, NA
"highlight2" >EMT↓,
"highlight2" >MSCmark↓,
"highlight2" >EM↑,
"highlight2" >STAT3↓,
"highlight2" >Zeb1↓,
"highlight2" >E-cadherin↑,

1120- 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, NA
"highlight2" >EMT↓,
"highlight2" >CSCs↓, cancer stem cell (CSC) properties
"highlight2" >TumCG↓,
"highlight2" >miR-141↑,

1153- HNK,    Honokiol Eliminates Glioma/Glioblastoma Stem Cell-Like Cells via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Factor Receptor
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vivo, NA, NA
"highlight2" >tumCV↓,
"highlight2" >Apoptosis↑,
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >Bcl-2↓,
"highlight2" >EGFR↓,
"highlight2" >CD133↓,
"highlight2" >Nestin↓,
"highlight2" >Akt↓,
"highlight2" >ERK↓,
"highlight2" >Casp3↑,
"highlight2" >p‑STAT3↓,
"highlight2" >TumCG↓, in vivo

1154- HNK,  MET,    Honokiol inhibits the growth of hormone-resistant breast cancer cells: its promising effect in combination with metformin
- in-vitro, BC, MCF-7 - in-vitro, BC, SkBr3 - in-vitro, BC, MDA-MB-231
"highlight2" >cl‑PARP↑,
"highlight2" >Bcl-2↓,
"highlight2" >ERα↓, combination of honokiol with metformin.

1286- HNK,    The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells
- in-vitro, CLL, NA
"highlight2" >Apoptosis↑,
"highlight2" >Casp3↑,
"highlight2" >Casp8↑,
"highlight2" >Casp9↑,
"highlight2" >cl‑PARP↑,
"highlight2" >Bcl-2↓,
"highlight2" >BAX↑,

2071- HNK,    Identification of senescence rejuvenation mechanism of Magnolia officinalis extract including honokiol as a core ingredient
- Review, Nor, HaCaT
"highlight2" >*ROS↓, Magnolia officinalis (M. officinalis) extract significantly lowered the levels of ROS in senescent fibroblasts.
"highlight2" >*antiOx↑, honokiol was demonstrated as a core ingredient of M. officinalis extract that exhibits antioxidant effects.
"highlight2" >*AntiAge↑, new approaches to anti–aging treatments
"highlight2" >*MMP↑, increases MMP
"highlight2" >*ECAR↓, senescent fibroblasts treated with M. officinalis extract had lower ECAR values than those treated with DMSO, suggesting that M. officinalis treatment lowed glycolysis rate
"highlight2" >*Glycolysis↓, honokiol, similar to M. officinalis, reduced the dependence of glycolysis as an energy source, indicating restoration of mitochondrial function by honokiol.
"highlight2" >*PAR-2↓, downregulation of PAR–2 expression by M. officinalis may reduce skin pigmentation.
"highlight2" >*CXCL12↑, upregulation of SDF–1 expression by M. officinalis may reduce skin pigmentation.
"highlight2" >*BMAL1↑, activation of Bmal–1 expression by M. officinalis promote skin turnover.
"highlight2" >*mt-ROS↓, compared to M. officinalis extract, honokiol at 1 and 10 μM was more effective in lowering mitochondrial ROS levels
"highlight2" >*OXPHOS↓, Inhibition of oxidative phosphorylation and induction of a compensatory shift toward glycolysis resulted in lower compensatory glycolysis in honokiol–treated senescent fibroblasts

2072- HNK,    Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells
- in-vitro, Thyroid, NA
"highlight2" >ROS↑, honokiol induced ROS activation
"highlight2" >eff↓, and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC).

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
"highlight2" >TumCD↑, honokiol caused dose-dependent and time-dependent cell death in human osteosarcoma cells
"highlight2" >TumAuto↑, death induced by honokiol were primarily autophagy and apoptosis.
"highlight2" >Apoptosis↑,
"highlight2" >TumCCA↑, honokiol induced G0/G1 phase arrest,
"highlight2" >GRP78/BiP↑, elevated the levels of glucose-regulated protein (GRP)−78, an endoplasmic reticular stress (ERS)-associated protein
"highlight2" >ROS↑, increased the production of intracellular reactive oxygen species (ROS)
"highlight2" >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.
"highlight2" >p‑ERK↑, honokiol stimulated phosphorylation of extracellular signal-regulated kinase (ERK)1/2.
"highlight2" >selectivity↑, human fibroblasts showed strong resistance to HNK, the IC50 values for which were 118.9 and 71.5 μM
"highlight2" >Ca+2↑, HNK increased intracellular Ca2+ in both HOS and U2OS cells
"highlight2" >MMP↓, mitochondrial membrane potential (MMP) sharply decreased following HNK treatment
"highlight2" >Casp3↑, HNK markedly activated caspase-3, caspase-9
"highlight2" >Casp9↑,
"highlight2" >cl‑PARP↑, led to PARP cleavage
"highlight2" >Bcl-2↓, expression of Bcl-2, Bcl-xl, and survivin was found to be decreased
"highlight2" >Bcl-xL↓,
"highlight2" >survivin↓,
"highlight2" >LC3B-II↑, HNK increased the level of LC3B-II and Atg5 in HOS and U2OS cells.
"highlight2" >ATG5↑,
"highlight2" >TumVol↓, HNK at doses of 40 mg/kg resulted in significant decrease in tumor volume and weight, after 7 days of drug administration
"highlight2" >TumW↓,
"highlight2" >ER Stress↑, ER stress can trigger ROS production through release of calcium

2079- HNK,    Honokiol Microemulsion Causes Stage-Dependent Toxicity Via Dual Roles in Oxidation-Reduction and Apoptosis through FoxO Signaling Pathway
- in-vitro, Nor, PC12
"highlight2" >*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.
"highlight2" >*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.
"highlight2" >*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.
"highlight2" >*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
"highlight2" >*BioAv↑, highly lipophilic property of honokiol allows it to readily cross the blood-brain barrier and blood-cerebrospinal fluid barrier with high bioavailability.
"highlight2" >*BioAv↓, However, this property also limits its clinical usage due to low oral bioavailability and difficulty in intravenous administration.
"highlight2" >*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
"highlight2" >*SOD↓, The activity of SOD showed only a slight reduction at 20 µM but was significantly reduced at 40 and 80 μM
"highlight2" >*toxicity↑, According to the human rat equivalent dosage conversion, the potential toxic dose in humans may be 320 µg/kg/d

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
"highlight2" >tumCV↓, honokiol decreased the viability of the targeted AML cells
"highlight2" >TumCCA↑, induced their cell cycle arrest at G0/G1 phase
"highlight2" >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.
"highlight2" >lipid-P↑,
"highlight2" >HO-1↑, HMOX1
"highlight2" >GPx4∅, Honokiol elevated the expression of HMOX1 but did not inhibit the expression of GPX4

960- HNK,    Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth
- vitro+vivo, BC, MCF-7 - vitro+vivo, BC, MDA-MB-231
"highlight2" >OCR↑, which resulted in an increase in OCR and a decrease in ECAR, glucose uptake, lactic acid production and ATP production.
"highlight2" >ECAR↓,
"highlight2" >GlucoseCon↓, decreased glucose uptake, lactate production and ATP production in cancer cells.
"highlight2" >lactateProd↓,
"highlight2" >ATP↓,
"highlight2" >Glycolysis↓,
"highlight2" >Hif1a↓,
"highlight2" >GLUT1↓,
"highlight2" >HK2↓,
"highlight2" >PDK1↓,
"highlight2" >Apoptosis↑,
"highlight2" >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

2082- HNK,    Revealing the role of honokiol in human glioma cells by RNA-seq analysis
- in-vitro, GBM, U87MG - in-vitro, GBM, U251
"highlight2" >AntiCan↑, In summary, studies have demonstrated that honokiol has multiple anticancer effects
"highlight2" >TumCP↑, honokiol suppresses cell proliferation, and promotes autophagy and apoptosis
"highlight2" >TumAuto↑,
"highlight2" >Apoptosis↑,
"highlight2" >*BioAv↑, honokiol could improve bioavailability in nerve tissue through passing the blood-brain barrie
"highlight2" >*neuroP↑, honokiol has neuroprotective effects.
"highlight2" >*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
"highlight2" >MAPK↑, honokiol activated cells MAPK signaling pathway in human glioma cells
"highlight2" >GPx4↑, The results showed that the ferroptosis-associated protein GPX4 was suppressed in honokiol-treated cells compared to control cells.
"highlight2" >Tf↑, Ferroptosis-associated protein TF was upregulated in both honokiol-treated cell lines compared to the control
"highlight2" >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.
"highlight2" >Bcl-2↓,
"highlight2" >antiOx↑, Researchers have found that the antioxidant capacity of honokiol is 1000 times greater than that of vitamin E
"highlight2" >Hif1a↓, reduce HIF-1α protein levels and suppress hypoxia-related signaling pathways
"highlight2" >Ferroptosis↑, Honokiol activated ferroptosis in human glioma cells

2863- HNK,    Honokiol induces paraptosis-like cell death through mitochondrial ROS-dependent endoplasmic reticulum stress in hepatocellular carcinoma Hep3B cells
- in-vitro, Liver, Hep3B
"highlight2" >ER Stress↑, Honokiol also enhanced ER stress, increased cellular calcium ion (Ca2+) levels, and caused mitochondrial dysfunction
"highlight2" >Ca+2↑,
"highlight2" >mtDam↑,
"highlight2" >PTEN↑, Honokiol upregulated the expression of mitophagy regulators such as PTEN-induced kinase 1 and Parkin in the mitochondria
"highlight2" >PARK2↑,
"highlight2" >Alix/AIP‑1↓, whereas the expression of apoptosis-linked gene 2-interacting protein X (Alix), involved in suppressing paraptosis, was downregulated.
"highlight2" >ROS↑, honokiol-induced cytotoxicity was accompanied by excessive generation of intracellular reactive oxygen species (ROS) and mitochondrial ROS (mtROS).
"highlight2" >mt-ROS↑,

2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
"highlight2" >TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
"highlight2" >CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
"highlight2" >EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
"highlight2" >MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
"highlight2" >AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
"highlight2" >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)
"highlight2" >TumCMig↓,
"highlight2" >TumMeta↓,
"highlight2" >VEGFR2↓,
"highlight2" >*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
"highlight2" >*Inflam↓,
"highlight2" >*BBB↑, Due to its ability to cross the blood–brain barrier
"highlight2" >*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
"highlight2" >*ROS↓,
"highlight2" >Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
"highlight2" >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
"highlight2" >Casp3↑, ↑ Caspase-3 & caspase-9
"highlight2" >Casp9↑,
"highlight2" >NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
"highlight2" >cycD1↓, ↓ cyclin D1 & c-Myc;
"highlight2" >cMyc↓,
"highlight2" >P21?, ↑ p21WAF1 protein
"highlight2" >DR5↑, ↑ DR5 & cleaved PARP
"highlight2" >cl‑PARP↑,
"highlight2" >P53↑, ↑ phosphorylated p53 & p53
"highlight2" >Mcl-1↑, ↓ Mcl-1 protein
"highlight2" >p65↓, ↓ p65; ↓ NF-κB
"highlight2" >NF-kB↓,
"highlight2" >ROS↑, ↑ JNK activation ,Increase ROS activity:
"highlight2" >JNK↑,
"highlight2" >NRF2↑, ↑ Nrf2 & c-Jun protein activation
"highlight2" >cJun↑,
"highlight2" >EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
"highlight2" >MAPK↓,
"highlight2" >PI3K↓,
"highlight2" >mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
"highlight2" >CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
"highlight2" >OCT4↓,
"highlight2" >Nanog↓,
"highlight2" >SOX4↓,
"highlight2" >STAT3↓,
"highlight2" >CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
"highlight2" >p‑RB1↓,
"highlight2" >PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
"highlight2" >COX2↓,
"highlight2" >β-catenin/ZEB1↑,
"highlight2" >IKKα↓, ↓ IKKα
"highlight2" >HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
"highlight2" >HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
"highlight2" >H3↑,
"highlight2" >H4↑,
"highlight2" >LC3II↑, ↑ LC3-II
"highlight2" >c-Raf↓, ↓ c-RAF
"highlight2" >SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
"highlight2" >Hif1a↓,
"highlight2" >ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
"highlight2" >GRP78/BiP↑,
"highlight2" >cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
"highlight2" >MMP↓, mitochondrial depolarization
"highlight2" >PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
"highlight2" >Zeb1↓, ↓ ZEB2 Inhibit
"highlight2" >NOTCH3↓, ↓ Notch3/Hes1 pathway
"highlight2" >CD133↓, ↓ CD133 & Nestin protein
"highlight2" >Nestin↓,
"highlight2" >ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
"highlight2" >ATG7↑,
"highlight2" >survivin↓, ↓ Mcl-1 & survivin protein
"highlight2" >ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
"highlight2" >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
"highlight2" >OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
"highlight2" >P-gp↓, 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
"highlight2" >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
"highlight2" >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.
"highlight2" >eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
"highlight2" >BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

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
"highlight2" >BioAv↓, poor water solubility of HNK results in its low bioavailability, thus limiting its wide use in clinical cancer treatments
"highlight2" >BioAv↓, Liposomes can overcome this limitation, and liposomal HNK (Lip-HNK) has promising clinical applications in this aspect
"highlight2" >TumCP↓, increased Lip-HNK concentration could inhibit the proliferation of DAOY and D283 cells, without exerting effects on the growth of non-tumor cells
"highlight2" >selectivity↑,
"highlight2" >P53↑, P53 and P21 proteins (inhibiting cell cycle progression) was increased
"highlight2" >P21↑,
"highlight2" >CDK4↓, Lip-HNK also downregulated the expression of CDK4 and cyclin D1
"highlight2" >cycD1↓,
"highlight2" >mtDam↑, Lip-HNK caused apoptosis and death, which, in turn, led to the failure of mitochondrial membrane function
"highlight2" >ROS↑, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
"highlight2" >eff↓, Lip-HNK induced ROS production, which, as hypothesized, was blocked by the ROS scavenger NAC
"highlight2" >Casp3↑, caspase-3 sectioned and the Bax protein level increased by Lip-HNK
"highlight2" >BAX↑,
"highlight2" >LC3II↑, LC3BII protein in the Lip-HNK-treated group was noticeably elevated
"highlight2" >Beclin-1↑, Beclin-1 (BECN), Atg7 proteins, and LC3BII were dramatically upregulated in the Lip-HNK-treated cells
"highlight2" >ATG7↑,
"highlight2" >p62↑, Lip-HNK treatment remarkably increased p62 expression, which was dose-dependent
"highlight2" >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
"highlight2" >ChemoSen↑, Lip-HNK alone or combined with chemotherapy (Carboplatin or Etoposide) causes significant regression of orthotopic xenografts
"highlight2" >*toxicity↓, We also found that Lip-HNK did not damage the liver and kidney

2866- HNK,    Honokiol and its analogues as anticancer compounds: Current mechanistic insights and structure-activity relationship
- Review, Var, NA
"highlight2" >EMT↓, Honokiol regulates oncogenic pathways, inhibits EMT, and prevents metastasis.
"highlight2" >TumMeta↓,
"highlight2" >BioAv↑, The hydrophobicity of honokiol enables its rapid dissolution in lipids
"highlight2" >BBB↑, crossing of physiological barriers, including the blood-brain barrier and cerebrospinal fluid

2867- HNK,    Honokiol ameliorates oxidative stress-induced DNA damage and apoptosis of c2c12 myoblasts by ROS generation and mitochondrial pathway
- in-vitro, Nor, C2C12
"highlight2" >*antiOx↑, known to have antioxidant activity, but its mechanism of action remains unclear.
"highlight2" >*ROS↓, honokiol inhibited hydrogen peroxide (H2O2)-induced DNA damage and mitochondrial dysfunction, while reducing reactive oxygen species (ROS) formation.
"highlight2" >*Bcl-2↑, up-regulation of Bcl-2 and down-regulation of Bax,
"highlight2" >*BAX↓,
"highlight2" >Casp9∅, in turn protected the activation of caspase-9 and -3, and inhibition of poly (ADP-ribose)
"highlight2" >Casp3∅,
"highlight2" >cl‑PARP∅,
"highlight2" >Cyt‑c?, e blocking of cytochrome c release to the cytoplasm

2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
"highlight2" >*P-gp↓, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6),
"highlight2" >*ROS↓,
"highlight2" >*TNF-α↓,
"highlight2" >*IL10↓,
"highlight2" >*IL6↓,
"highlight2" >eIF2α↑, Bcl-2, phosphorylated eIF2α, CHOP,GRP78, Bax, cleaved caspase-9 and phosphorylated PERK
"highlight2" >CHOP↑,
"highlight2" >GRP78/BiP↑,
"highlight2" >BAX↑,
"highlight2" >cl‑Casp9↑,
"highlight2" >p‑PERK↑,
"highlight2" >ER Stress↑, endoplasmic reticulum stress and proteins in apoptosis in 95-D and A549 cells
"highlight2" >Apoptosis↑,
"highlight2" >MMPs↓, decrease in levels of matrix metal-mloproteinases, P-glycoprotein expression, the formation of mammosphere, H3K27 methyltransferase, c-FLIP, level of CXCR4 receptor,pluripotency-factors, Twist-1, class I histone deacetylases, steroid receptor co
"highlight2" >cFLIP↓,
"highlight2" >CXCR4↓,
"highlight2" >Twist↓,
"highlight2" >HDAC↓,
"highlight2" >BMPs↑, enhancement in Bax protein, and (BMP7), as well as interference with an activator of transcription 3 (STAT3), (mTOR), (EGFR), (NF-kB) and Shh
"highlight2" >p‑STAT3↓, secreased the phosphorylation of STAT3
"highlight2" >mTOR↓,
"highlight2" >EGFR↓,
"highlight2" >NF-kB↓,
"highlight2" >Shh↓,
"highlight2" >VEGF↓, induce apoptosis, and regulate the vascular endothelial growth factor-A expression (VEGF-A)
"highlight2" >tumCV↓, human glioma cell lines (U251 and U-87 MG) through inhibition of colony formation, glioma cell viability, cell migration, invasion, suppression of ERK and AKT signalling cascades, apoptosis induction, and reduction of Bcl-2 expression.
"highlight2" >TumCMig↓,
"highlight2" >TumCI↓,
"highlight2" >ERK↓,
"highlight2" >Akt↓,
"highlight2" >Bcl-2↓,
"highlight2" >Nestin↓, increased the Bax expression, lowered the CD133, EGFR, and Nesti
"highlight2" >CD133↓,
"highlight2" >p‑cMET↑, HKL through the downregulating the phosphorylation of c-Met phosphorylation and stimulation of Ras,
"highlight2" >RAS↑,
"highlight2" >chemoP↑, Cheng and coworker determined the chemopreventive role of HKL against the proliferation of renal cell carcinoma (RCC) 786‑0 cells through multiple mechanism
"highlight2" >*NRF2↑, , HKL also effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in in vivo and in vitro model
"highlight2" >*NADPH↓, (HUVECs) such as inhibition of NADPH oxidase activity, suppression of p22 (phox) protein expression, Rac-1 phosphorylation, reactive oxygen species production, inhibition of degradation of Ikappa-B-alpha, and suppression of activity of of NF-kB
"highlight2" >*p‑Rac1↓,
"highlight2" >*ROS↓,
"highlight2" >*IKKα↑,
"highlight2" >*NF-kB↓,
"highlight2" >*COX2↓, Furthermore, HKL treatment the inhibited cyclooxygenase (COX-2) upregulation, reduces prostaglandin E2 production, enhanced caspase-3 activity reduction
"highlight2" >*PGE2↓,
"highlight2" >*Casp3↓,
"highlight2" >*hepatoP↑, compound also displayed hepatoprotective action against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 liver cells in in vitro model
"highlight2" >*antiOx↑, compound reduces the level of acetylation on SOD2 to stimulate its antioxidative action, which results in reduced reactive oxygen species aggregation in AML12 cells
"highlight2" >*GSH↑, HKL prevents oxidative damage induced by H2O2 via elevating antioxidant enzymes levels which includes glutathione and catalase and promotes translocation and activation transcription factor Nrf2
"highlight2" >*Catalase↑,
"highlight2" >*RenoP↑, imilarly, the compound protects renal reperfusion/i-schemia injury (IRI) in adult male albino Wistar rats via reducing theactivities of serum alkaline phosphatase (ALP), aspartate aminotrans- ferase (AST) and alanine aminotransferase (ALT)
"highlight2" >*ALP↓,
"highlight2" >*AST↓,
"highlight2" >*ALAT↓,
"highlight2" >*neuroP↑, Several reports and works have shown that HKL displays some neuroprotective properties
"highlight2" >*cardioP↑, Cardioprotection
"highlight2" >*HO-1↑, the expression level of heme oxygenase-1 (HO-1)was remarkably up-regulated and miR-218-5p was significantly down-regulated in septic mice treated with HKL
"highlight2" >*Inflam↓, anti-inflammatory action of HKL at dose of 10 mg/kg in the muscle layer of mice

2869- HNK,    Nature's neuroprotector: Honokiol and its promise for Alzheimer's and Parkinson's
- Review, AD, NA - Review, Park, NA
"highlight2" >*neuroP↑, neuroprotective, anti-oxidant, anti-apoptotic, neuromodulating, anti-inflammatory, and many more qualities, honokiol,
"highlight2" >*Inflam↓,
"highlight2" >*motorD↑, degradation of dopaminergic neurons in Parkinson's disease and improving motor function.
"highlight2" >*Aβ↓, Alzheimer's disease, honokiol showed promise in lowering the production of amyloid-beta (Aβ) plaques, phosphorylating tau, and enhancing cognitive performance
"highlight2" >*p‑tau↓,
"highlight2" >*cognitive↑,
"highlight2" >*memory↑, prevented Acetylcholinesterase activity from elevation as well as improved acetylcholine levels, and improved learning, and memory deficits via increased ERK1/2 and Akt phosphorylation
"highlight2" >*ERK↑,
"highlight2" >*p‑Akt↑,
"highlight2" >*PPARγ↑, honokiol has been reported to elevate PPARγ levels in APPswe/PS1dE9 mice as PPARγ is related to ani-inflammatory
"highlight2" >*PGC-1α↑, honokiol boosted the expression of PGC1α and PPARγ
"highlight2" >*MMP↑, as well as reduced elevated mitochondrial membrane potential and mitochondrial ROS
"highlight2" >*mt-ROS↓,
"highlight2" >*SIRT3↑, Honokiol has been found as a dual SIRT-3 activator and PPAR-γ agonist that reduced oxidative stress markers within cells and changed the AMPK pathway
"highlight2" >*IL1β↓, honokiol prevented restraint stress-induced cognitive dysfunction by reducing the hippocampus's production of IL-1β, TNF-α, glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP)
"highlight2" >*TNF-α↓,
"highlight2" >*GRP78/BiP↓,
"highlight2" >*CHOP↓,
"highlight2" >*NF-kB↓, Additionally, the neuroprotective benefits of honokiol in mice with Aβ-induced learning and memory impairment have been attributed to the inactivation of NF-κB
"highlight2" >*GSK‐3β↓, Treatment of honokiol in PC12 cells resulted in reduced GSK-3β and induced β-catenin which effectively showed the neuroprotective and anti-oxidant effect in AD therapy
"highlight2" >*β-catenin/ZEB1↑,
"highlight2" >*Ca+2↓, , anti-apoptotic effect via reduced caspase 3 levels, and protected membrane injury by reduced calcium level has been investigated in PC12 cells of AD models
"highlight2" >*AChE↓, protective effects by serving as an antioxidant, reduced AchE levels, repaired neurofibrillary tangles, reduced NF-kB which downregulates Aβ plaque
"highlight2" >*SOD↑, fig1
"highlight2" >*Catalase↑,
"highlight2" >*GPx↑,

2870- HNK,    Honokiol attenuates oxidative stress and vascular calcification via the upregulation of heme oxygenase-1 in chronic kidney disease
- in-vitro, CKD, NA
"highlight2" >*HO-1↑, Mechanistically, HKL upregulated heme oxygenase-1 (HMOX-1), thereby inhibiting oxidative stress and reducing calcification
"highlight2" >*ROS↓, HKL ameliorates VC by upregulating HMOX-1 and decreasing oxidative stress.

2871- HNK,    Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling
- in-vivo, Nor, NA
"highlight2" >*TNF-α↓, honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF).
"highlight2" >*IL1β↓,
"highlight2" >*IL6↓,
"highlight2" >*VEGF↓,
"highlight2" >*NRF2↑, honokiol was also found to potentiate the expression of nuclear factor erythroid 2–related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels.
"highlight2" >*SOD2↑,
"highlight2" >*HO-1↑,
"highlight2" >*Inflam↓, honokiol reduced the inflammation
"highlight2" >*Pain↓, honokiol might be a promising candidate as a new treatment for pain. results showed that honokiol remarkably reduced pain response throughout the chronic inflammatory pain model
"highlight2" >*NO↓, Honokiol significantly reduced NO production after 6 days of treatment
"highlight2" >toxicity↓, Treating mice with honokiol for 6 days showed no visible sign of toxicity or ill health. Obtained values, which were used as an indicator of liver and renal function, are shown in the table

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
"highlight2" >*eff↑, Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease
"highlight2" >*ROS↓, honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway.
"highlight2" >*GSH↑,
"highlight2" >*NRF2↑,
"highlight2" >*motorD↑, Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function
"highlight2" >*OS↑,
"highlight2" >*neuroP↑, honokiol exerted neuroprotection in ALS models.
"highlight2" >*BBB↑, due to its strong lipophilic property, honokiol can readily permeate the blood–brain barrier and blood–cerebrospinal fluid barrier.
"highlight2" >*cognitive↑, honokiol was shown a beneficial effect on the cognitive impairment in APP/PS1 via ameliorating the mitochondrial dysfunction
"highlight2" >*eff↑, Furthermore, honokiol was applied for patent (200310121303.0) for ischemic stroke treatment, and the clinical trials would be started soon in China
"highlight2" >*antiOx↑, Honokiol showed strong antioxidant capacity in vitro and protected the yeast against H2O2 induced oxidative damage
"highlight2" >*Cyt‑c↑, cytoplasmic release of cytochrome c was markedly decreased
"highlight2" >*PGC-1α↑, 10 μmol/L and significantly upregulated the PGC-1α, NRF1, and TFAM protein

2873- HNK,    Honokiol Alleviates Oxidative Stress-Induced Neurotoxicity via Activation of Nrf2
- in-vitro, Nor, PC12
"highlight2" >*neuroP↑, multiple pharmacological functions, including neuroprotection.
"highlight2" >*GSH↑, Hon attenuates the H2O2- or 6-hydroxydopamine (6-OHDA)-induced apoptosis of PC12 cells by increasing the glutathione level
"highlight2" >*HO-1↑, and upregulating a multitude of cytoprotective proteins, including heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, thioredoxin 1, and thioredoxin reductase 1.
"highlight2" >*NADPH↑,
"highlight2" >*Trx1↑,
"highlight2" >*TrxR1↑,
"highlight2" >*NRF2↑, Hon promotes transcription factor Nrf2 nuclear translocation and activation.
"highlight2" >*ROS↓, Hon is promising for further development as a therapeutic drug against oxidative stress-related neurodegenerative disorders. Inhibition of ROS accumulation
"highlight2" >*antiOx↑, Upregulation of antioxidant species in PC12 cells
"highlight2" >*BBB↑, Hon has the ability to cross the BBB
"highlight2" >Dose↓, We demonstrated here that Hon, at the concentration as low as 5 μM, significantly rescues the cells from H2O2- or 6-OHDA-induced oxidative damage

2874- HNK,    Suppressing migration and invasion of H1299 lung cancer cells by honokiol through disrupting expression of an HDAC6‐mediated matrix metalloproteinase 9
- in-vitro, Lung, H1299
"highlight2" >MMP9↓, Honokiol‐inhibited MMP‐9 expression was through promoting MMP‐9 protein degradation rather than suppressing transcription mechanism
"highlight2" >α-tubulin↑, Furthermore, the expression of specific histone deacetylases 6 (HDAC6) substrate, acetyl‐α‐tubulin, was accumulated after honokiol incubation.
"highlight2" >TumCI↓, honokiol‐suppressed MMP‐9 expression and invasion ability of H1299 lung cancer cells
"highlight2" >HDAC6↓, Honokiol‐suppressed MMP‐9 expression was through the inhibition of HDAC6/Hsp90 signaling pathway
"highlight2" >HSP90↓,
"highlight2" >TumCMig↓, Honokiol inhibited lung cancer cell migration and invasion
"highlight2" >EGFR↓, Honokiol has been verified to inhibit the EGFR‐mediated signaling pathwa


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 56

Results for Effect on Cancer/Diseased Cells:
Akt↓,8,   Alix/AIP‑1↓,1,   AMP↑,1,   AMPK↑,2,   angioG↓,2,   AntiCan↑,2,   antiOx↑,2,   Apoptosis↑,13,   ATG5↑,2,   ATG7↑,2,   ATP↓,2,   BAX↑,4,   BBB↓,1,   BBB↑,2,   Bcl-2↓,6,   Bcl-xL↓,1,   Beclin-1↑,1,   BioAv↓,4,   BioAv↑,2,   BioAv↝,1,   BMPs↑,2,   Ca+2↑,4,   Casp3↑,9,   Casp3∅,1,   Casp7↑,1,   Casp8↑,2,   Casp9↑,4,   Casp9∅,1,   cl‑Casp9↑,1,   CD133↓,3,   CD4+↑,1,   CD8+↑,1,   CDK2↓,4,   CDK4↓,5,   CDK6↓,1,   CEBPB↓,1,   cFLIP↓,3,   chemoP↑,5,   ChemoSen↑,6,   CHOP↑,1,   cl‑CHOP↑,1,   cJun↑,1,   p‑cMET↑,1,   cMyc↓,1,   COX2↓,6,   CSCs↓,2,   cSrc↓,1,   CXCR4↓,1,   cycD1↓,5,   cycE↓,1,   Cyt‑c↑,3,   Cyt‑c?,1,   DNAdam↑,1,   Dose↓,1,   Dose↝,1,   DR5↑,1,   E-cadherin↑,5,   ECAR↓,2,   EF-1α↓,1,   eff↓,3,   eff↑,5,   EGFR↓,8,   eIF2α↑,1,   p‑eIF2α↑,1,   EM↑,1,   EMT↓,10,   ER Stress↑,6,   ERK↓,3,   p‑ERK↑,1,   ERα↓,1,   EZH2↓,1,   Ferroptosis↑,3,   Foxm1↓,1,   GlucoseCon↓,1,   GLUT1↓,1,   Glycolysis↓,1,   GPx4↓,1,   GPx4↑,1,   GPx4∅,1,   GRP78/BiP↑,3,   H3↑,1,   ac‑H3↑,1,   H4↑,1,   ac‑H4↑,1,   Half-Life↓,1,   Half-Life↝,3,   HATs↑,1,   HDAC↓,3,   HDAC3↓,1,   HDAC6↓,2,   HER2/EBBR2↓,1,   Hif1a↓,7,   HK2↓,1,   HO-1↓,1,   HO-1↑,1,   HSP90↓,3,   IFN-γ↓,1,   IKKα↓,1,   IKKα↑,1,   IL1β↓,1,   IL6↓,1,   Inflam↓,3,   Iron↑,1,   JAK1↓,1,   JAK2↓,1,   JNK↑,1,   lactateProd↓,1,   LC3B-II↑,1,   LC3II↑,2,   LDHA↓,1,   lipid-P↑,1,   MAPK↓,1,   MAPK↑,1,   Mcl-1↓,1,   Mcl-1↑,1,   miR-141↑,1,   mitResp↓,2,   MMP↓,2,   MMP2↓,3,   MMP9↓,6,   MMPs↓,2,   MSCmark↓,1,   mtDam↑,4,   mTOR↓,5,   p‑mTOR↓,2,   mTORC1↓,1,   N-cadherin↓,4,   NA↑,1,   NADPH↓,1,   Nanog↓,1,   Nestin↓,3,   neuroP↑,1,   NF-kB↓,9,   NO↝,1,   NOTCH1↓,1,   NOTCH3↓,1,   NRF2↑,1,   OCR↓,2,   OCR↑,2,   OCT4↓,1,   OS↑,1,   P-gp↓,2,   P21?,1,   P21↑,3,   p27↑,1,   P53↑,2,   p62↑,1,   p65↓,2,   p70S6↓,1,   PARK2↑,1,   cl‑PARP↑,5,   cl‑PARP∅,1,   PCNA↓,1,   PD-L1↓,2,   PDK1↓,1,   p‑PERK↑,1,   PGE2↓,4,   PI3K↓,7,   Prx3↑,1,   PTEN↑,2,   RadioS↑,3,   c-Raf↓,1,   RAS↓,3,   RAS↑,1,   p‑RB1↓,1,   Rho↓,1,   Rho↑,1,   ROCK1↓,1,   ROCK1↑,1,   ROS↑,9,   mt-ROS↑,4,   selectivity↑,8,   Shh↓,1,   SIRT1↑,1,   SIRT3↑,5,   Slug↓,2,   p‑SMAD2↓,2,   p‑SMAD3↓,2,   Snail↓,5,   ac‑SOD2↓,1,   SOX2↓,1,   SOX4↓,1,   STAT3↓,4,   p‑STAT3↓,3,   mt-STAT3↓,1,   survivin↓,2,   T-Cell↑,1,   Tf↑,1,   TNF-α↓,2,   TNF-α↑,1,   toxicity↓,2,   TumAuto↑,2,   TumCCA↑,9,   TumCD↑,1,   TumCG↓,3,   TumCI↓,10,   TumCMig↓,10,   TumCP↓,6,   TumCP↑,1,   tumCV↓,8,   TumMeta↓,5,   TumVol↓,2,   TumW↓,2,   Twist↓,2,   VEGF↓,4,   VEGFR2↓,1,   Vim↓,3,   Wnt↓,2,   Zeb1↓,2,   α-tubulin↑,2,   β-catenin/ZEB1↓,3,   β-catenin/ZEB1↑,1,  
Total Targets: 212

Results for Effect on Normal Cells:
AChE↓,1,   p‑Akt↑,1,   ALAT↓,1,   ALP↓,1,   AntiAg↑,1,   AntiAge↑,1,   antiOx↑,8,   AST↓,1,   ATP↑,1,   Aβ↓,2,   BAX↓,1,   BBB↑,4,   Bcl-2↑,1,   BioAv↓,2,   BioAv↑,2,   BMAL1↑,1,   Ca+2↓,1,   cardioP↑,5,   Casp3↓,2,   Catalase↑,2,   CHOP↓,1,   cognitive↑,2,   COX2↓,1,   CXCL12↑,1,   Cyt‑c↑,1,   Dose⇅,1,   ECAR↓,1,   eff↑,2,   ERK↓,1,   ERK↑,1,   Glycolysis↓,1,   Glycolysis↑,1,   GPx↑,1,   GRP78/BiP↓,1,   GSH↑,4,   GSK‐3β↓,1,   hepatoP↑,1,   HO-1↑,4,   IKKα↑,1,   IL10↓,1,   IL1β↓,2,   IL6↓,2,   Inflam↓,6,   Keap1↑,1,   LDH↓,1,   memory↑,3,   mitResp↑,2,   MMP↑,4,   motorD↑,2,   NADPH↓,1,   NADPH↑,1,   neuroP↑,8,   NF-kB↓,3,   NF-kB↑,1,   NO↓,1,   NRF2↑,5,   OS↑,1,   OXPHOS↓,1,   OXPHOS↑,1,   P-gp↓,1,   Pain↓,1,   PAR-2↓,1,   PGC-1α↑,4,   PGE2↓,1,   PPARα↑,1,   PPARγ↑,4,   p‑Rac1↓,1,   radioP↑,1,   RenoP↑,1,   Rho↓,1,   ROS↓,18,   ROS↑,1,   ROS⇅,1,   mt-ROS↓,2,   SIRT3↑,5,   SOD↓,1,   SOD↑,1,   SOD2↑,3,   p‑tau↓,1,   TNF-α↓,3,   toxicity↓,2,   toxicity↑,1,   toxicity↝,1,   toxicity∅,1,   Trx↑,1,   Trx1↑,1,   TrxR1↑,2,   VEGF↓,1,   β-catenin/ZEB1↑,1,  
Total Targets: 89

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