Coptisine

Coptisine is an orally active and brain-penetrant alkaloid found in Coptis chinensis. Coptisine is a reversible, uncompetitive IDO inhibitor with a K_i of 5.8 μM and an IC₅₀ of 6.3 μM. Coptisine suppresses neuroinflammation, reduces Aβ plaque burden and shows neuroprotective activity. Coptisine shows anti-inflammation activity by blocking NF-κB, MAPK, and PI3K/Akt activation. Coptisine inhibits cancer cells proliferation, induces DNA damage, G2/M phase cell cycle arrest, apoptosis, ROS production and mitochondrial dysfunction. Coptisine inhibits Rho/ROCK pathway activation, reduces arrhythmia, limits cardiac injury marker release, reduces infarct size, and preserves cardiac function in rat myocardial ischemia/reperfusion models. Coptisine downregulates HMGCR and upregulates LDLR and CYP7A1 to modulate cholesterol metabolism, reduces abnormal serum lipid levels, and promotes fecal bile acid excretion. Coptisine can be used for the research of cancer, hypercholesterolemia, Alzheimer’s disease, inflammatory disorders and cardiovascular disease^{[1][2][3][4][5]}. IC50 & Target:IC50: 6.3 μM (IDO)^[1]
Ki: 5.8 μM (IDO)^[1] In Vitro:Coptisine (0.1-100 μM; 48 h) potently inhibits proliferation of human lung adenocarcinoma A5499, H460,
and H2170 cells (IC₅₀ = 18.09, 29.50, and 21.60 μM) and other tested human cancer cell lines, with moderate selectivity relative to normal human umbilical vein endothelial cells^[1].
Coptisine (12.5-50 μM; 48 h) induces concentration-dependent DNA damage in human lung adenocarcinoma A549 cells, as shown by increased γH2AX expression^[1].
Coptisine (12.5-50 μM; 48 h) induces concentration-dependent G2/M phase cell cycle arrest in human lung adenocarcinoma A549 cells, mediated by downregulated cyclin B1, cdc2, and cdc25C expression and upregulated p21 expression^[1].
Coptisine (12.5-50 μM; 48 h) induces concentration-dependent apoptosis in human lung adenocarcinoma A549 cells, inducing concentration-dependent activation of caspase 3/7, caspase 8, caspase 9, and cleavage of PARP^[1].
Coptisine (12.5-50 μM; 0.5-24 h) induces time- and concentration-dependent reactive oxygen species generation in human lung adenocarcinoma A549 cells^[1].
Coptisine (12.5-50 μM; 24 h) induces concentration-dependent mitochondrial dysfunction in human lung adenocarcinoma A549 cells, including loss of mitochondrial membrane potential and altered Bax, Bcl-2, and cytochrome c expression^[1].
Coptisine potently inhibits recombinant human IDO as a reversible, uncompetitive inhibitor with a K_i of 5.8 μM and an IC₅₀ of 6.3 μM^[4].
Coptisine inhibits IDO activity in HEK 293 cells with an IC₅₀ of 7.1 μM^[4].
Coptisine (10 μM; 5 h pre-incubation) reverses amyloid-β peptide 1-42 and interferon-γ-induced IDO activation and restores cell viability in PC12 cells^[4].
Coptisine inhibits LPS (HY-D1056)-stimulated inflammation by blocking NF-κB, MAPK, and PI3K/Akt activation in
macrophages^[5]. In Vivo:Coptisine (10-30 mg/kg; p.o.; single dose 10 min before ischemia or plus additional dose 4 h after reperfusion) exerts pronounced cardioprotective effects against rat myocardial ischemia/reperfusion injury by reducing arrhythmias, infarct size, cardiac enzyme release, and left ventricular dysfunction, while suppressing myocardial apoptosis, inflammation, and Rho/ROCK pathway activation^[2].
Coptisine (23.35-70.05 mg/kg/day; i.g.; daily; 4 weeks) dose-dependently improves hypercholesterolemia in HFHC-fed Syrian golden hamsters^[3].
Coptisine (482.5-1728 mg/kg; p.o.; single dose) has low acute toxicity in Kunming mice, with an LD₅₀ of 880.18 mg/kg following a single oral dose^[3].
Coptisine (154 mg/kg/day; p.o.; daily; 90 days) is well-tolerated in SD rats with no observable toxicity via daily oral administration for 90 days^[3].
Coptisine (50 mg/kg; p.o.; once daily; 1 month) normalizes serum IDO activity, suppresses neuroinflammation, reduces Aβ plaque burden, restores neuronal integrity, and completely reverses cognitive impairment in A-PPswe/PS1ΔE9 transgenic Alzheimer's disease mice^[4].
Coptisine attenuates obesity-related inflammation through LPS/TLR-4-mediated signaling pathway in Syrian golden hamsters^[5].