Jatrorrhizine

Jatrorrhizine is an alkaloid isolated from Coptis chinensis with neuroprotective, antimicrobial, antiplasmodial and antioxidant activities^[1]. Jatrorrhizine is a potent and orally active inhibitor of AChE (IC₅₀=872 nM) over >115-fold selectivity for BuChE^[2]. Jatrorrhizine reduces uptake of serotonin (5-HT) and norepinephrine (NE) via inhibition of uptake-2 transporters^[3]. IC50 & Target: IC50: 872 nM (AChE)^[1] In Vitro: Jatrorrhizine has antiplasmodial and antiamoebic activity, it against Plasmodium falciparum and E. histolytica with IC₅₀ values of 3.15 and 82.7 µM, respectively^[1].
The hOCT2 (organic cation transporter 2), hOCT3, and PMAT (plasma membrane monoamine transporter) are capable of transporting monoamine neurotransmitters in the brain^[3].
Jatrorrhizine has the inhibitory potency of jatrorrhizine on 5-HT and NE uptake in hOCT2-, hOCT3-, and PMAT-transfected cells. Jatrorrhizine strongly inhibits PMAT-mediated MPP⁺ uptake with an IC₅₀ value of 1.05 μM and reduces 5-HT and NE uptake mediated by hOCT2, hOCT3, and hPMAT with IC₅₀ values of 0.1-1 μM (for OCT2 and OCT3) and 1-10 μM (for PMAT)^[3].
Clearance of neurotransmitters released into the synaptic cleft is defined by two distinct processes. Uptake-1, the common target of current applied antidepressants, is comprised of the serotonin transporter (SERT), the “SERT”, had a high affinity but low capacity to take up [3H]5-HT. Uptake-2 transporters are an important supplementary regulation system in monoamine clearancethought to be the “NET”, has low affinity but high capacity to take up [³H]5-HT into brain slices.
Jatrorrhizine significantly inhibited 5-HT and NE uptake in synaptosomes at 25 μM and 50 μM^[3].
In Vivo: Jatrorrhizine (intraperitoneal injection; 5, 10, 20 mg/kg) can significantly reduce the duration of immobility when compared with vehicle control group in tail suspension test (TST)^[2].