Hispidulin is a naturally occurring flavonoid with a wide range of bioactivities. Hispidulin is an inhibitor (blocker/antagonist) of Pim-1 with IC50 of 2.71 μM.

Physicochemical Properties

Molecular Formula	C16H12O6
Molecular Weight	300.27
Exact Mass	300.063
Elemental Analysis	C, 64.00; H, 4.03; O, 31.97
CAS #	1447-88-7
PubChem CID	5281628
Appearance	Light yellow to yellow solid powder
Density	1.5±0.1 g/cm3
Boiling Point	601.5±55.0 °C at 760 mmHg
Flash Point	230.1±25.0 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.697
LogP	1.6
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	2
Heavy Atom Count	22
Complexity	454
Defined Atom Stereocenter Count	0
SMILES	COC1=C(C2=C(C=C1O)OC(=CC2=O)C3=CC=C(C=C3)O)O
InChi Key	IHFBPDAQLQOCBX-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H12O6/c1-21-16-11(19)7-13-14(15(16)20)10(18)6-12(22-13)8-2-4-9(17)5-3-8/h2-7,17,19-20H,1H3
Chemical Name	5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxychromen-4-one
Synonyms	NSC122415; NSC-122415; Hispidulin; 1447-88-7; Dinatin; Scutellarein 6-methyl ether; 4',5,7-Trihydroxy-6-methoxyflavone; 4H-1-BENZOPYRAN-4-ONE, 5,7-DIHYDROXY-2-(4-HYDROXYPHENYL)-6-METHOXY-; Salvitin; 5,7-dihydroxy-2-(4-hydroxyphenyl)-6-methoxychromen-4-one; NSC 122415; Dinatin; Hispidulin
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	Proto - oncogene kinase Pim - 1 (IC50 = 2.71 μM) Phosphatidylinositol 3 - kinase (PI3K)、Akt AMP - activated protein kinase (AMPK)
ln Vitro	HispiduLin causes dose- and time-dependent cell death in HepG2 cells. Through mitochondrial function, hispiduLin causes cellular problems that are typified by increased release of pigment C and activated Capase-3, disturbance of the potential of the mitochondrial membrane, and reduced Bcl-2/Bax [2]. Hispidulin shows inhibitory activity against Pim - 1 kinase. In HepG2 cancer cells, hispidulin induces apoptosis in a dose - and time - dependent manner. It causes mitochondrial dysfunction, characterized by a decreased Bcl - 2/Bax ratio, disrupted mitochondrial membrane potential, and increased release of cytochrome c and activation of caspase - 3. It also inhibits the PI3K/Akt signaling pathway.
ln Vivo	The size of mice tumors is significantly inhibited by HispiduLin [2]. Treatment with HispiduLin effectively reduces bone loss from late resection and stops weight loss from ovariectomy. Treatment with HispiduLin also decreased ovariectomy trabeculae. Thirty minutes before to intraperitoneal injection of HispiduLin (10 or 50 mg/kg), kainic acid (15 mg/kg) infusion increased the predicted incubation period and decreased prediction scores. Moreover, HispiduLin has far less data. Hippocampal neuronal cell death is caused by radotoxin, and this protective effect is accompanied by pro-inflammatory cytokines such apoptotic factor-α, interleukin-1β, and interleukin-6, as well as tumor suppression by astrocyte activators[4]. In ovariectomized mice, hispidulin exerts anti - osteoporotic activity by activating the AMPK signaling pathway, which can mitigate body and bone loss and reduce trabecular spacing. In a rat model of kainic acid - induced seizures, hispidulin (10 or 50 mg/kg) is administered intraperitoneally 30 minutes before kainic acid injection (15 mg/kg). It can increase seizure latency, lower seizure scores, reduce hippocampal neuronal cell death, diminish microglial activation, and decrease the production of pro - inflammatory cytokines (interleukin - 1β, interleukin - 6, and tumor necrosis factor - α) in the hippocampus.
Cell Assay	HepG2 cancer cells are cultured and treated with different concentrations of hispidulin for different time periods. Then, the expression levels of Bcl - 2, Bax, cytochrome c, and caspase - 3 are detected by Western blot. The mitochondrial membrane potential is measured using a mitochondrial membrane potential detection kit. Meanwhile, the activation status of the PI3K/Akt signaling pathway is evaluated by detecting the phosphorylation levels of related proteins through Western blot.
Animal Protocol	For ovariectomized mice, hispidulin is dissolved in an appropriate solvent and administered to the mice, and the specific administration frequency is not mentioned. The experimental period is long - term, and finally, the body weight, bone mass, and trabecular structure of the mice are detected. For rats, hispidulin is dissolved in an appropriate solvent and intraperitoneally injected at a dose of 10 or 50 mg/kg, 30 minutes before kainic acid injection (15 mg/kg). Then, the seizure latency and scores are recorded, and after the experiment, the hippocampal tissues are collected to detect neuronal cell death, microglial activation, and the levels of pro - inflammatory cytokines.
References	[1]. Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene KinasePim-1. J Nat Prod. 2015 Aug 28;78(8):1969-76. [2]. Hispidulin induces apoptosis through mitochondrial dysfunction and inhibition of P13k/Akt signalling pathway in HepG2 cancer cells. Cell Biochem Biophys. 2014 May;69(1):27-34. [3]. Hispidulin exerts anti-osteoporotic activity in ovariectomized mice via activating AMPK signaling pathway. Cell Biochem Biophys. 2014 Jun;69(2):311-7. [4]. Protective effect of hispidulin on kainic acid-induced seizures and neurotoxicity in rats. Eur J Pharmacol. 2015 May 15;755:6-15.
Additional Infomation	Hispidulin is a natural flavone with a broad spectrum of biological activities. Hispidulin is a monomethoxyflavone that is scutellarein methylated at position 6. It has a role as an apoptosis inducer, an anti-inflammatory agent, an antioxidant, an anticonvulsant, an antineoplastic agent and a plant metabolite. It is a trihydroxyflavone and a monomethoxyflavone. It is functionally related to a scutellarein. Hispidulin (4',5,7-trihydroxy-6-methoxyflavone) is a potent benzodiazepine (BZD) receptor ligand with positive allosteric properties. Hispidulin has been reported in Salvia plebeia, Bejaranoa balansae, and other organisms with data available. See also: Arnica montana Flower (part of).

Solubility Data

Solubility (In Vitro)

DMSO : ~62.5 mg/mL (~208.15 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.93 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 20.8 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: ≥ 2.08 mg/mL (6.93 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 20.8 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: ≥ 2.08 mg/mL (6.93 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 10 mg/mL (33.30 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.3303 mL	16.6517 mL	33.3034 mL
	5 mM	0.6661 mL	3.3303 mL	6.6607 mL
	10 mM	0.3330 mL	1.6652 mL	3.3303 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.