Miquelianin

Biological Activity

In vitro: Miquelianin shows an antioxidant effect in human plasma. At 50 μM, miquelianin suppresses the consumption of the three antioxidants lycopene, β-carotene and α-tocopherol significantly. In vitro studies indicate that miquelianin is able to reach the central nervous system from the small intestine. Miquelianin significantly reduces the generation of β-amyloid (Aβ) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. It is also capable of interfering with the initial protein-protein interaction of Aβ1–40 and Aβ1–42 that is necessary for the formation of neurotoxic oligomeric Aβ species. Treatment with 0.1 μM miquelianin suppresses ROS generation, cAMP and RAS activation, phosphorylation of ERK1/2 and the expression of HMOX1, MMP2, and MMP9 genes. Miquelianin suppresses invasion of MDA-MB-231 breast cancer cells and MMP-9 induction, and inhibits the binding of [3H]-NA to b2-AR. Miquelianin may function to suppress invasion of breast cancer cells by controlling b2-adrenergic signaling, and may be a dietary chemopreventive factor for stress-related breast cancer. In vivo: Miquelianin treatment, compared to vehicle-control treatment, significantly improves AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation. A flavonoid fraction obtained from a crude extract of Hypericum perforatum (St. John's wort) is remarkably active in the forced swimming test. Miquelianin is one of the compound separated from the fraction.

Protocol (for reference only)

Cell Experiment
Cell lines	14–16 corticohippocampal neuronal
Preparation method	Freshly isolated low-molecular-weight Aβ1–42 (25 μM) or Aβ1–40 (25 μM) peptide (18 μl) was mixed with 1 μl of 1 mm tris-(2,2′-bipyridyl)dichlororuthenium(II) [Ru(Bpy)] and 1 μl of 20 mM ammonium persulfate in the presence or absence of 25 μM quercetin-3-O-glucuronide in 10 mM phosphate.
Concentrations	25 μM
Incubation time

Animal Experiment
Animal models	Tg2576 mice
Formulation
Dosages
Administration

Chemical Information

Molecular Weight	478.36
Formula	C21H18O13
CAS Number	22688-79-5
Solubility (25°C)	30 mg/mL in DMSO
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Yang HH, et al. Arch Pharm Res. Quercetin-3-O-β-D-glucuronide isolated from Polygonum aviculare inhibits cellular senescence in human primary cells.

[2] Ho L, et al. FASEB J. Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease.