Chao Dong

Noncovalent interactions of 4 selected phenolic acids, including gallic acid (GA), caffeic acid (CA), chlorogenic acid (CGA), and rosmarinic acid (RA) with lactoferrin (LF) were investigated. Compound combined with LF in the binding constant of CA > GA > RA > CGA, driven by van der Waals and hydrogen bonding for GA, and hydrophobic forces for others. Conformation of LF was affected at secondary and ternary structure levels. Molecular docking indicated that GA and CA located in the same site near the iron of the C-lobe, whereas RA and CGA bound to the C2 and N-lobe, respectively. Significantly enhanced antioxidant activity of complexes was found compared with pure LF, as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis(2-ethylbenzothiazoline-6-sulfonate) (ABTS), and ferric reducing antioxidant power (FRAP) models. Caffeic acid, CGA, and RA significantly decreased the emulsifying stability index and improved foam ability of LF, and the effect of CA and RA was the most remarkable, respectively.

The development of angiotensin II (Ang II)-induced cardiomyopathies is reportedly mediated via oxidative stress and inflammation. Nuclear factor erythroid 2-related factor (Nrf2) is an important regulator of cellular antioxidant defense, and reactive oxygen species (ROS) can activate the NLRP3 inflammasome. MHRT is a newly discovered lncRNA exhibiting cardioprotective effects, demonstrated by inhibiting myocardial hypertrophy via Brg1 and myocardial apoptosis via Nrf2 upregulation. However, the underlying mechanism of MHRT remains unclear. We explored the potential protective effects of MHRT against Ang II-induced myocardial oxidative stress and NLRP3-mediated inflammation by targeting Nrf2. Chronic Ang II administration induced NLRP3 inflammasome activation (increased NLRP3, caspase-1 and interleukin-1β expression), oxidative stress (increased 3-nitrotyrosine and 4-hydroxy-2-nonenal), cardiac dysfunction and decreased MHRT and Nrf2 expression. Lentivirus-mediated MHRT overexpression inhibited Ang II (100 nM)-induced oxidative stress and NLRP3 inflammasome activation in AC16 human cardiomyocyte cells. Mechanistically, MHRT overexpression upregulated the expression and function of Nrf2, as determined by the increased transcription of downstream genes HO-1 and CAT, subsequently decreasing intracellular ROS accumulation and inhibiting the expression of thioredoxin-interacting protein (NLRP3 activator) and its direct binding to NLRP3. Accordingly, MHRT could protect against Ang II-induced myocardial injury by decreasing oxidative stress and NLRP3 inflammasome activation via Nrf2 activation.