Imperatorin

Imperatorin is an effective of NO synthesis inhibitor (IC₅₀=9.2 μmol), which also is a BChE inhibitor (IC₅₀=31.4 μmol). Imperatorin is a weak agonist of TRPV1 with EC₅₀ of 12.6±3.2 μM. IC50 & Target: IC50: 9.2 μmol (NO synthesis), 31.4 μmol (BChE)^[1] EC50: 12.6±3.2 μM (TRPV1)^[2] In Vitro: Imperatorin is a plant secondary metabolite belonging to the coumarins-specifically the furanocoumarins. Imperatorin enhances the GABA-induced chloride ion current (I_GABA) through the α₁β₂γ_2S receptors. Imperatorin potentiates I_GABA at 100 μmol by 50.5±16.3 % and at 300 μmol by 109.8±37.7 %, respectively. Imperatorin, together with Phellopterin, found in the roots of A. dahurica, inhibit [³H]diazepam binding to the benzodiazepine site of the rat brain GABA_A receptor in vitro with an IC₅₀ of 12.3 μmol for Imperatorin and 400 nmol for Phellopterin. Imperatorin, in a concentration ranging from 3.5 to 14 mmol, significantly and irreversibly inhibits GABA-T in a time-dependent and concentration-dependent manner, by irreversibly binding with the active site of GABA-T.Imperatorin is a reversible acetylcholinesterase (AChE) inhibitor, and acts in dose-dependent manner. The AChE and BChE inhibitory activities of Imperatorin and a crude extract from the fruits of Angelica archangelica L. is tested by the spectrophotometric method at concentrations of 12.5, 25, 50, and 100 μg/mL. Imperatorin displays low inhibition towards AChE (13.75-46.11 %), whereas it has remarkable inhibitory effect against BChE (37.46-83.98 %). Imperatorin shows selectivity toward BChE rather than AChE, with an IC₅₀ for BChE of 31.4 μmol. Imperatorin, together with (+)-Byakangelicol, are found to be the most effective BACE-1 inhibitors, with IC₅₀s of 91.8 and 104.9 μmol, respectively. Imperatorin (IC₅₀=9.2 μmol) is also effective as an inhibitor of NO synthesis^[1]. Imperatorin is a weak agonist of TRPV1, a channel implicated in detecting several noxious stimuli, exhibiting EC₅₀ of 12.6±3.2 μM^[2]. In Vivo: At doses of 10 and 20 mg/kg and 30 min after injection, Imperatorin shows an anxiolytic effect and improved different stages of memory and learning processes-both acquisition and consolidation. It is also shown that acute administration Imperatorin at doses of 10 and 20 mg/kg reduced the anxiogenic effect of nicotine (0.1 mg/kg, subcutaneous, s.c.). At 30 and 40 mg/kg, i.p. Imperatorin significantly potentiates the anticonvulsant activity of carbamazepine against maximal electroshock-induced seizures expressed by lowering the ED₅₀ from 10.8 to 6.8 mg/kg (by 34 %) and 6 mg/kg (by 42 %), respectively. Moreover, Imperatorin at 30 mg/kg and carbamazepine at 6.8 mg/kg shows increases the total brain concentration of carbamazepine from 1.260 to 2.328 μg/mL (by 85%), which may be caused by modifying the blood-barrier permeability or acting like an inhibitor of multi-drug resistance proteins^[1]. Imperatorin, a naturally occurring furanocoumarin, inactivates gamma-aminobutyric acid transaminase and inhibits acetylcholinesterase activity. Imperatorin administered acutely at the doses of 5 and 10 mg/kg prior to the injection of scopolamine (1 mg/kg) improves memory acquisition and consolidation impaired by scopolamine. Furthermore, repeatable (7 days, twice daily) administration of the highest dose of Imperatorin (10 mg/kg) significantly attenuates the effects of scopolamine on memory acquisition, whereas the doses of 5 and 10 mg/kg of this furanocoumarin are effective when memory consolidation is measured ^[3].