Imperatorin (8-Isopentenyloxypsoralene) is a modulator of p38, ERK pathway. Imperatorin increases BMP-2 expression (mRNA) and increases bone density/volume and mineralization in vivo.

TRPV1:12.6±3.2 μM(EC50), BChE:31.4 μm

Imperatorin, a furanocoumarin plant secondary metabolite, enhances GABA-induced chloride ion current (IGABA) via α1β2γ2S receptors, potentiating IGABA at 100 μmol by 50.5±16.3% and at 300 μmol by 109.8±37.7%. Found in A. dahurica roots alongside Phellopterin, Imperatorin inhibits [3H]diazepam binding to the rat brain GABAA receptor benzodiazepine site in vitro, with IC50 values of 12.3 μmol and 400 nmol, respectively. At concentrations of 3.5 to 14 mmol, Imperatorin significantly and irreversibly inhibits GABA-T in a time- and concentration-dependent manner. It also acts as a dose-dependent, reversible acetylcholinesterase (AChE) inhibitor and shows low AChE inhibition (13.75-46.11%) but significant butyrylcholinesterase (BChE) inhibition (37.46-83.98%) with an IC50 of 31.4 μmol. Imperatorin, along with (+)-Byakangelicol, is a potent BACE-1 inhibitor with IC50 values of 91.8 μmol and 104.9 μmol, respectively, and acts as an inhibitor of NO synthesis (IC50=9.2 μmol). Additionally, Imperatorin is a weak agonist of TRPV1, exhibiting an EC50 of 12.6±3.2 μM.

Administered at doses of 10 and 20 mg/kg and observed 30 minutes post-injection, Imperatorin demonstrates anxiolytic properties alongside enhancements in memory and learning stages, both acquisition and consolidation. Furthermore, at these dosages, Imperatorin acutely mitigates the anxiety-inducing effects of nicotine (0.1 mg/kg, subcutaneous, s.c.). At increased doses of 30 and 40 mg/kg, intraperitoneally, Imperatorin notably augments the anticonvulsant efficacy of carbamazepine against maximal electroshock-induced seizures, evidenced by a substantial reduction in the effective dose 50 (ED50) of carbamazepine from 10.8 to 6.8 mg/kg (by 34%) and to 6 mg/kg (by 42%), respectively. Additionally, a combination of Imperatorin at 30 mg/kg and carbamazepine at 6.8 mg/kg elevates the total brain concentration of carbamazepine from 1.260 to 2.328 μg/mL (by 85%), potentially through alterations in blood-brain barrier permeability or as an inhibitor of multi-drug resistance proteins. As a naturally occurring furanocoumarin, Imperatorin deactivates gamma-aminobutyric acid transaminase and hinders acetylcholinesterase activity. When administered acutely in doses of 5 and 10 mg/kg prior to scopolamine (1 mg/kg), it counters the memory acquisition and consolidation impairments induced by scopolamine. Repeated administration (7 days, twice daily) of Imperatorin at the highest studied dose (10 mg/kg) significantly diminishes scopolamine’s adverse effects on memory acquisition, with doses of 5 and 10 mg/kg proving effective in memory consolidation.