Nevadensin

Nevadensin (Lysionotin), a natural flavonoid, is a selective human carboxylesterase 1 (hCE1) inhibitor with an IC₅₀ of 2.64 μM. Nevadensin is more selective for hCE1 than hCE2 (IC₅₀ of 132.8 μM). Nevadensin can induce apoptosis and DNA damage in cancer cells. Nevadensin has a variety of pharmacological effects such as anti-inflammatory, anti-tumour, anti-hypertensive, anti-tubercular, antitussive, antioxidant and anti-microbial activities^{[1][2][3][4][5]}. IC50 & Target:IC50: 2.64 μM (hCE1), 132.8 μM (hCE2)^[1] In Vitro:Nevadensin exhibits inhibition activity against Mycobacterium tuberculosis, with a MIC value of 200 μg/mL. Nevadensin exhibits antioxidant activity against the radical scavenging ability of DPPH, with the IC₅₀ value of 7.7 μg/mL^[2].
Nevadensin potently inhibits p40 protein tyrosine kinase activity with an IC₅₀ value of 50 μg/mL^[3].
Nevadensin shows DNA-intercalating properties, with IC₅₀s of 31.63 µM and 296.91 µM for minor groove binding and DNA intercalation^[3].
Nevadensin (500 μM; 1 h) in human colon carcinoma cell line HT29 cells, significantly increases the amount of topoisomerase I (TOPO I) bound to DNA, but has no stabilizing effect on the TOPO IIα/DNA complex^[3].
Nevadensin (1-500 μM; 24-48 h) in HT29 cells, causes a slight but significant reduction in cell viability of about 20% at concentrations ≥250 μM after 24 h, and a significant decrease in cell viability but still higher than 50% after 48 h^[3].
Nevadensin (1-500 μM; 24 h) in HT29 cells, increases the number of cells in the G2/M phase at concentrations ≥100 μM^[3].
Nevadensin (50-500 μM; 24 h) in HT29 cells, increases the activities of caspase-3 and caspase-9 in a concentration-dependent manner and has no effect on the activity of caspase-8^[3].
Nevadensin (12.5-50 µM; for 24 h) significantly inhibits growth of hepatocellular carcinoma (HCC) cells via inducing cell cycle arrest and apoptosis. Nevadensin regulates multiple functional signaling pathways associated with cancer including Hippo signaling. Nevadensin notably induces activation of the MST1/2-LATS1/2 kinase in HCC cells^[4].
Nevadensin (1-10 μg/mL) inhibits the release of β-hexosaminidase and histamine in bone marrow-derived mast cells^[5].
Nevadensin (2-20 μg/mL; 3 days) in BMMCs (bone marrow-derived mast cells) inhibits cell proliferation, decreases the expression of c-Kit and accelerates their apoptosis^[5].
In Vivo:Nevadensin (1-10 mg/kg; gavage; once a day; from day 27 to day 40) in ovalbumin (OVA)-induced mouse food allergy model alleviates allergic symptoms and decreases the levels of serum specific immunoglobulin E, histamine, and mouse mast cell protease-1^[5].