Hypaconitine

Hypaconitine inhibits the KCNH2 current with an IC₅₀ of 8.1 nM, and exhibits cardiotoxicity. Hypaconitine inhibits TGF-β1-induced epithelial-mesenchymal transition (EMT) in A549 cell through the inhibition of NF-κB nuclear translocation. Hypaconitine acts as the neuromuscular blocker. Hypaconitine is orally active^[1][2][3][4]. In Vitro:Hypaconitine (0-8 μM, 48 h) reverses TGF-β1-induced cell morphological changes (such as the disappearance of intercellular junctions and the appearance of spindle-shaped appearance), reverses the conversion of E-cadherin to N-cadherin in TGF-β1 administrated A549 cell and H1299 cell, reverses TGF-β1-induced cell migration and invasion of cell A549 and H1299^[1].
Hypaconitine (10-60 μM, 24 h) regulates the calcium influx and calcium release through store-operated Ca²⁺ channels, and exhibits cytotoxicity in HCN-2 neuronal cells^[3].
Hypaconitine (0-5 μM, 60 min) inhibits nerve-evoked twitch tension and nerve compound action potential in phrenic mouse diaphragm cells^[4]. In Vivo:Hypaconitine (50-450 μg/kg, po, single dose) prolongs the QT interval in conscious beagle dog models, exhibits potential cardiotoxicity^[2].