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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 |
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Chemokine Receptor Type 4 (CXCR4) is a G protein-coupled receptor that plays a significant role in various physiological processes, including immune responses, hematopoiesis, and organ development. It is also implicated in cancer biology, where it has been associated with tumor progression, metastasis, and the tumor microenvironment. CXCR4 is often overexpressed in various types of cancers, including breast, lung, prostate, and pancreatic cancers. Its activation can promote tumor cell proliferation and survival. -CXCR4 proteins associated with metastasis |
2868- | HNK,  |   | Honokiol: A review of its pharmacological potential and therapeutic insights |
- | Review, | Var, | NA | - | Review, | Sepsis, | NA |
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