Imperatorin is a naturally occuring multiple-target inhibitor of NOS with IC50 value of 9.2 μM, BChE with IC50 value of 31.4 μM, a potent calcium antagonist on vascular smooth muscle. It is also a weak agonist of TRPV1 with EC50 of 12.6±3.2 μM.
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[3]. Imperatorin can activate RUNX2, COL1A1 and osteocalcin by promoting the Ser9 phosphorylation of GSK3β and entry of β-catenin into the nucleus. Intragastric administration of imperatorin promoted osteogenesis and inhibited osteoclast in vivoYan DY, Tang J, Chen L, Wang B, Weng S, Xie Z, Wu ZY, Shen Z, Bai B, Yang L. Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β-catenin pathways. J Cell Mol Med. 2020 Feb;24(3):2330-2341|https://pubmed.ncbi.nlm.nih.gov/31883297Yan DY, Tang J, Chen L, Wang B, Weng S, Xie Z, Wu ZY, Shen Z, Bai B, Yang L. Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β-catenin pathways. J Cell Mol Med. 2020 Feb;24(3):2330-2341|https://pubmed.ncbi.nlm.nih.gov/31883297. Imperatorin is a weak agonist of TRPV1, a channel implicated in detecting several noxious stimuli, exhibiting a 50% effective concentration (EC50) of 12.6 ± 3.2 μM[4]. Imperatorin administered acutely at the doses of 5 and 10 mg/kg prior to the injection of scopolamine (1 mg/kg) improved memory acquisition and consolidation impaired by scopolamine. Furthermore, repeatable (7 days, twice daily) administration of the highest dose of imperatorin (10 mg/kg) significantly attenuated the effects of scopolamine on memory acquisition, whereas the doses of 5 and 10 mg/kg of this furanocoumarin were effective when memory consolidation was measured. Imperatorin, administered with scopolamine, increased antioxidant enzymes activity and decreased concentration of malondiamide, an indicator of lipid peroxidation level[5]. Imperatorin inhibited HIF-1α (hypoxia-inducible factor-1) protein synthesis by downregulating the mTOR/p70S6K(ribosomal protein S6 kinase)/4E-BP1 (eIF4E binding protein-1) and MAPK pathways[6].
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