Sinigrin Selectively Mitigates the Acute-Cardiac Inflammatory Response Through an AMPK-Dependent Mechanism

Inflammatory cardiomyopathy is an inflammatory condition characterised by infiltrating inflammatory cells into the heart, which causes impaired myocardial function. Sinigrin (SNG) has been reported to possess antioxidant and anti-inflammatory properties. This study aimed to investigate the therapeutic benefit of SNG against endotoxin/Poly(I:C)-induced acute-cardiac inflammation using in vitro and in vivo models. Experimental procedure: THP-1, HCF and H9C2 cells were employed as an in vitro model, while lipopolysaccharide (LPS)/Poly(I:C)-induced cardiac inflammation model served as an in vivo to examine the anti-inflammatory potential of SNG using molecular biology techniques, cardiac function and histological assessments. The network pharmacological approach revealed that SNG could target the myocarditis-responsible genes. mRNA/protein expression studies showed that SNG treatment significantly mitigated the LPS + Poly(I:C)-induced expression of pro-inflammatory and myocarditis-responsive genes. Further analysis revealed that SNG treatment significantly reduced the LPS + Poly(I:C)-induced elevation of neutrophil, lymphocyte count, AST, ALT, LDH and CK-MB levels; infiltration of inflammatory cells, cardiomyocyte degeneration, cardiac troponin and macrophage markers, on the other hand, improved the platelet levels. Cardiac functional parameters by Langendorff indicated that SNG potentially ameliorated the LPS + Poly(I:C)-induced elevation of LVP and other parameters and improved cardiac functions. Molecular docking studies demonstrated that sinigrin forms a H-bond with Asn-111 (significant interaction) and binds to the activator site of AMPK with a docking score of -8.88 kcal/mol. The current study reveals that sinigrin exerts potent anti-inflammatory and antioxidant activities by modulating AMPK signalling. These findings support sinigrin's potential as a promising option for treating acute myocardial inflammation and open avenues for translational research.