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Jatrorrhizine is a potent and orally active uptake-2 transporter inhibitor, it can be isolated from various Chinese medicinal plants[1]. Jatrorrhizine exhibits a critical neuroprotective role in H2O2-induced apoptosis via inhibition of MAPK pathway in HT22 hippocampal neurons[2].

Organic cation transporters (OCTs) and the plasma membrane monoamine transporter (PMAT) are major uptake-2 transporters[1].Jatrorrhizine significantly inhibits the plasma membrane monoamine transporter (PMAT) -mediated MPP+ uptake in a concentration-dependent manner with an IC50 value of 1.05 μM[1].Jatrorrhizine demonstrates a more powerful inhibition on serotonin (5-HT) and norepinephrine (NE) uptake mediated by hOCT2 and hOCT3 than that mediated by PMAT[1].Jatrorrhizine attenuates the H2O2-induced Bcl-2/Bax ratio reduction and caspase-3 activation in these neurons[2].

[1]. Sun S, et al. Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice. Xenobiotica. 2019 Oct;49(10):1237-1243.

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