Neuropharmacological Effects of Mesaconitine: Evidence from Molecular and Cellular Basis of Neural Circuit

Abstract

Mesaconitine (MA), a diester-diterpenoid alkaloid in aconite roots, is considered to be one of the most important bioactive ingredients. In this review, we summarized its neuropharmacological effects, including analgesic effects and antiepileptiform effects. Mesaconitine can act on the central noradrenergic system and the serotonin system; behaving like the norepinephrine reuptake inhibitors and tricyclic antidepressants that increase norepinephrine levels in stress-induced depression. Therefore, the possible perspectives for future studies on the depression of MA were also discussed as well. The pharmacological effect of MA on depression is worthy of further study.

Figure 1

Absolute stereochemistry of mesaconitine and catabolite.

Figure 2

Schematic drawing of the nociceptive system with ascending and descending fibers. RF: reticular formation; PAG: periaqueductal gray; NRM: nucleus raphe magnus; NRGC: nucleus reticularis gigantocellularis; NRPG: nucleus reticularis paragigantocellularis; NRL: nucleus reticularis lateralis; 5-HT: 5-hydroxytryptamine; ENK: enkephalin; NA: noradrenaline.

Figure 3

Schematic drawing of the antiepileptiform mechanism of mesaconitine on a noradrenergic neuron in the pyramidal stratum of the hippocampus.

Figure 4

Role of β-adrenoceptors on antidepressant effect. All arrows indicate activation arrows. Gs: stimulating adenylate cyclase g protein; ATP: adenosine triphosphate; AC: adenylate cyclase; cAMP: cyclic adenosine monophosphate; PKA: protein kinase A; CREB: cAMP-response element-binding protein; BDNF: brain-derived neurotrophic factor; LTP: long-term potentiation; AMPA: α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor.