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.

Imperatorin is a plant secondary metabolite that belongs to the coumarins-specifically the furanocoumarins. Imperatorin enhances the GABA-induced chloride ion current (IGABA) via the α1β2γ2S receptors. Imperatorin potentiates IGABA 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 GABAA 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].

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.