Honokiol (also known as NSC 293100) is a bioactive, biphenolic phytochemical that occurs naturally. It is the active component of magnolia extract and has powerful anti-inflammatory, anti-oxidative, anti-cancer, and anti-inflammatory properties. It prevents the phosphorylation of ERK1/2 and promotes the phosphorylation of ERK1/ERK2, which prevents the phosphorylation of Akt. The bark or seed cones of the Magnolia tree are used to make the natural product honokiol. As a traditional analgesic and treatment for anxiety and mood disorders, houpu has been used in eastern medicine. As a potent and extremely tolerable antitumorigenic and neurotrophic compound, honokiol experienced a resurgence in popularity in the late 1990s. Honokiol has strong anti-inflammatory, anti-oxidative, anti-cancer, and anti-angiogenic properties that it uses to target different signaling molecules.

Physicochemical Properties

Molecular Formula	C18H18O2
Molecular Weight	266.334
Exact Mass	266.13
Elemental Analysis	C, 81.17; H, 6.81; O, 12.01
CAS #	35354-74-6
Related CAS #	35354-74-6(Honokiol)
PubChem CID	72303
Appearance	White to off-white solid powder
Density	1.1±0.1 g/cm3
Boiling Point	400.1±40.0 °C at 760 mmHg
Melting Point	87.5ºC
Flash Point	184.0±21.9 °C
Vapour Pressure	0.0±1.0 mmHg at 25°C
Index of Refraction	1.602
LogP	4.2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	5
Heavy Atom Count	20
Complexity	325
Defined Atom Stereocenter Count	0
SMILES	O([H])C1C([H])=C([H])C(C([H])([H])C([H])=C([H])[H])=C([H])C=1C1C([H])=C([H])C(=C(C([H])([H])C([H])=C([H])[H])C=1[H])O[H]
InChi Key	FVYXIJYOAGAUQK-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H18O2/c1-3-5-13-7-9-18(20)16(11-13)14-8-10-17(19)15(12-14)6-4-2/h3-4,7-12,19-20H,1-2,5-6H2
Chemical Name	2-(4-hydroxy-3-prop-2-enylphenyl)-4-prop-2-enylphenol
Synonyms	Honokiol, Houpa; Hnk
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	ERK1; ERK2; Autophagy
ln Vitro	Honokiol exhibits pro-apoptotic effects in melanoma, sarcoma, myeloma, leukemia, bladder, lung, prostate, oral squamous cell carcinoma, and colon cancer cell lines. Honokiol is effective at causing apoptosis in SVR angiosarcoma cells. When honokiol is used to treat SVR cells, less MAP kinase, akt, and c-src are phosphorylated. Additionally, TRAIL-mediated apoptosis is potentiated by honokiol, and the cytotoxicity of honokiol is partially reversed by TRAIL-neutralizing antibodies. Honokiol also has direct antiangiogenic properties, as it prevents phosphorylation and rac activation brought on by VEGF-VEGFR2 interactions.[1] Honokiol activates caspase 8, which is followed by caspase 9, and then it activates caspase 3 to cause apoptosis in CLL cells. Honokiol inhibits the interleukin-4-mediated survival of CLL cells and increases the cytotoxicity of chlorambucil, fludarabine, and cladribine. [3] Honokiol kills myeloma cells from relapsed patients at doses that do not kill PBMCs. Treatment with honokiol and PARP cleavage both induce caspases 3, 7, 8, and 9.[2] Honokiol has been found to cause apoptosis in the colon cancer cell lines RKO. [4] By modifying the nuclear factor-kappaB activation pathway, honokiol promotes apoptosis, inhibits osteoclastogenesis, and prevents invasion. Honokiol has an inhibitory effect on the PI3K/Akt pathway, which may make it a potent anti-inflammatory drug with a variety of potential uses.[6]
ln Vivo	Honokiol is very successful in treating SVR angiosarcoma in naked mice. [1] In murine xenografts, honokiol prevents the growth of RKO cells. [4] In murine xenografts, honokiol inhibits the growth of MDA-MD-231 breast cancer cells. [7]
Cell Assay	In cytotoxicity tests, 96-well plates with 10,000 cells per well are added and allowed to stand overnight before the cells are exposed to various Honokiol concentrations dissolved in DMSO. For in vitro studies, honokiol is dissolved in DMSO because it is not soluble in aqueous solvents. Solvent (DMSO) control is used at a maximum concentration of <0.1% to investigate the potential impact of DMSO on cells. Cells are fixed 72 hours after treatment, and crystal violet staining (0.05%) is used to assess cell viability.
Animal Protocol	The MDA-MB-231 cells (2 million) are injected into mammary fat tissue for anticancer in vivo studies. Palpable tumors are seen in mammary tissues two weeks after the tumor cell injections, which is a sign that a tumor has formed. The medication is then administered orally at doses of 40 and 80 mg/kg per day, either in free form or in nanomicellar form. The drug treatment is continued for another four weeks, and weekly weight and tumor volume measurements are made. Animals are sacrificed after 4 weeks of treatment, and the final tumor weights and volumes are assessed. For immunohistochemical and western blot analyses, these tumors are used.
References	[1]. J Biol Chem . 2003 Sep 12;278(37):35501-7. [2]. Blood . 2005 Sep 1;106(5):1794-800. [3]. Blood . 2005 Jul 15;106(2):690-7. [4]. World J Gastroenterol . 2004 Aug 1;10(15):2205-8. [5]. https://pubmed.ncbi.nlm.nih.gov/16966432/ [6]. Acta Pharmacol Sin . 2008 Jan;29(1):113-22. [7]. Int J Oncol . 2007 Jun;30(6):1529-37. [8]. Eur J Pharmacol . 2005 Jun 1;516(2):112-7.
Additional Infomation	Honokiol is a member of biphenyls. Honokiol has been reported in Magnolia officinalis, Illicium simonsii, and other organisms with data available.

Solubility Data

Solubility (In Vitro)

DMSO: ~53 mg/mL (~199.0 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (9.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 2% DMSO+40% PEG 300+2% Tween 80+ddH2O: 2mg/mL Solubility in Formulation 5: 16.67 mg/mL (62.59 mM) in Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.7547 mL	18.7737 mL	37.5474 mL
	5 mM	0.7509 mL	3.7547 mL	7.5095 mL
	10 mM	0.3755 mL	1.8774 mL	3.7547 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.