Nicotianamine

Nicotianamine is an orally active ACE inhibitor with an IC₅₀ of 76 nM for rhACE2 and an IC₅₀ of 59 nM for rhACE. Nicotianamine is also a metal chelator with high affinity for ferrous ions and other divalent metal cations. Nicotianamine is isolated from soybean. Nicotianamine reduces systolic blood pressure in spontaneously hypertensive rats. Nicotianamine chelates iron and zinc, promotes iron transport, enhances iron bioavailability through stable Fe²⁺-NA complexes and intestinal Fe²⁺ uptake, and promotes phloem-to-sink Fe mobilization, long-distance transport of Zn to leaves and flowers, and pollen development. Nicotianamine is a biosynthetic precursor of plant phytosiderophores, reverses chlorosis, and rescues sterility in NA-free mutants. Nicotianamine is used in research on hypertension, chlorosis, and iron deficiency anemia^{[1][2][3][4][5][6]}. In Vitro:Nicotianamine inhibits rhACE2 activity with an IC₅₀ of 76 nM^[1].
Nicotianamine inhibits rhACE activity with an IC₅₀ of 59 nM^[1].
Nicotianamine inhibits ACE with an IC₅₀ of 0.26 µM^[2].
Nicotianamine (1 h) inhibits rabbit lung ACE activity with an IC₅₀ of 0.69 μM in a cell-free enzymatic assay^[3].
Synthetic Nicotianamine (30 µM; daily for seven days) reverts the chlorotic phenotype and restores normal growth in the NA-free tomato mutant chloronerva^[4].
Nicotianamine (5 µM; daily) application rescues sterility in Arabidopsis thaliana nas4x-2 mutant plants^[6]. In Vivo:Nicotianamine (20 mg/kg; single dose) reduces blood pressure by 24, 20, and 19 mmHg at 1 h, 4 h, and 8 h, respectively, in spontaneously hypertensive rats^[2].
Nicotianamine (0.9-9.0 mg/kg; p.o.; single dose) significantly reduces systolic blood pressure at 1 h after administration in SHR rats, with the effect returning to control levels at 3 h^[3].
Nicotianamine (9.0 mg/kg; p.o.; daily; 8 weeks) produces a sustained antihypertensive effect in SHR, maintaining a 23.4 mmHg reduction in SBP throughout the 8-week feeding period, which correlates with a serum NA concentration of 32.6 μg/dL^[3].