condition found tbRes List
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


ROCK1, Rho-associated coiled-coil containing protein kinase 1: Click to Expand ⟱
Source:
Type:
ROCK1 (Rho-associated coiled-coil containing protein kinase 1)
– ROCK1 is a serine/threonine kinase and a major effector of the Rho GTPase signaling pathway.

– Elevated expression of ROCK1 has been observed in various cancers, including breast, prostate, lung, colorectal, and gastric cancers.

– In many tumors, ROCK1 overexpression correlates with increased cell motility, invasion, and metastatic potential.
Scientific Papers found: Click to Expand⟱
2882- HNK,    Honokiol Suppresses Perineural Invasion of Pancreatic Cancer by Inhibiting SMAD2/3 Signaling
- in-vitro, PC, PANC1
TumCI↓, HNK can inhibit the invasion and migration of pancreatic cancer cells.
TumCMig↓,
p‑SMAD2↓, partially mediated by inhibition of SMAD2/3 phosphorylation.
p‑SMAD3↓,
EMT↓, HNK Inhibits Pancreatic Cancer Malignant Behaviors and EMT
N-cadherin↓, expression of N-cadherin and Vimentin was gradually downregulated, while HNK promoted the expression of E-cadherin in PANC-1
Vim↓,
E-cadherin↑,
Snail↓, HNK can inhibit breast cancer cell metastasis by blocking EMT through downregulating Snail/Slug protein translation
Slug↓,
Rho↓, Honokiol inhibits the migration of renal cell carcinoma through activation of the RhoA/ROCK/MLC signaling pathway
ROCK1↓,

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↑, 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↓,
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↓, 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


* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 2

Results for Effect on Cancer/Diseased Cells:
Akt↓,1,   angioG↓,1,   BMPs↑,1,   CDK2↓,1,   CDK4↓,1,   CDK6↓,1,   cFLIP↓,1,   cycD1↓,1,   E-cadherin↑,1,   ECAR↓,1,   EMT↓,1,   Foxm1↓,1,   Hif1a↓,1,   HO-1↓,1,   MMP2↓,1,   mTOR↓,1,   N-cadherin↓,1,   NF-kB↓,1,   OCR↑,1,   P-gp↓,1,   P21↑,1,   p27↑,1,   PI3K↓,1,   RAS↓,1,   Rho↓,1,   Rho↑,1,   ROCK1↓,1,   ROCK1↑,1,   Slug↓,1,   p‑SMAD2↓,1,   p‑SMAD3↓,1,   Snail↓,1,   TumCI↓,1,   TumCMig↓,2,   Twist↓,1,   VEGF↓,1,   Vim↓,1,  
Total Targets: 37

Results for Effect on Normal Cells:
AntiAg↑,1,   antiOx↑,1,   Aβ↓,1,   BBB↑,1,   BioAv↓,1,   cardioP↑,1,   Casp3↓,1,   ERK↓,1,   Keap1↑,1,   memory↑,1,   neuroP↑,1,   NF-kB↓,1,   NRF2↑,1,   PGC-1α↑,1,   PPARγ↑,1,   Rho↓,1,   ROS↓,2,   SIRT3↑,1,  
Total Targets: 18

Scientific Paper Hit Count for: ROCK1, Rho-associated coiled-coil containing protein kinase 1
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:94  Target#:1284  State#:%  Dir#:%
  wNotes=on  sortOrder:rid,rpid

 

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