Corynoline

Corynoline is an isoquinoline alkaloid that has been found in C. incisa and has diverse biological activities.^1,2,3,4,5 It is an inhibitor of acetylcholinesterase (IC₅₀ = 30.6 µM) and β-secretase 1 (BACE1; IC₅₀s = 33.59 and 89.07 µM for FRET and immobilized enzyme reactive assays, respectively).^1,2 Corynoline (1-4 µM) decreases LPS-induced NF-κB activation and further increases LPS-induced increases in Nrf2 and heme oxygenase-1 (HO-1) protein levels in human umbilical vein endothelial cells (HUVECs).³ It increases the survival rate in a mouse model of LPS- and heat-killed E. coli-induced sepsis when administered at doses of 10, 20, and 40 mg/kg.⁴ Corynoline selectively inhibits proliferation of B16/F10 mouse and A375 human melanoma cells (IC₅₀s = 12.87 and 10.47 µM, respectively) over non-cancerous melanocytes (IC₅₀ = 126.61 µM).⁵ It halts the cell cycle at the G₂ phase and induces apoptosis and the production of reactive oxygen species (ROS) in a dose-dependent manner in the same cells. It also reduces tumor growth in a B16/F10 mouse melanoma model when administered at a dose of 20 mg/kg.

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1. Kim, D.K. Inhibitory effect of corynoline isolated from the aerial parts of Corydalis incisa on the acetylcholinesterase. Arch. Pharm. Res. 25(6), 817-819 (2002).

2. Chlebek, J., Simone, A.D., Hošt'álková, A., et al. Application of BACE1 immobilized enzyme reactor for the characterization of multifunctional alkaloids from Corydalis cava (Fumariaceae) as Alzheimer’s disease targets. Fitoterapia 109, 241-247 (2016).

3. Liu, B., Su, K., Wang, J., et al. Corynoline exhibits anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells through activating Nrf2. Inflammation 41(5), 1640-1647 (2018).

4. He, Z.-B., Chen, P., Peng, Z.-Y., et al. Effect of corynoline isolated from Corydalis bungeana turcz on lipopolysaccharides-induced sepsis in vivo and in vitro. Trop. J. Pharm. Res. 13(1), 81-86 (2014).

5. Yi, C., Li, X., Chen, S., et al. Natural product corynoline suppresses melanoma cell growth through inducing oxidative stress. Phytother. Res. (2020).