6‐Gingerol Ameliorates ISO‐Induced Myocardial Fibrosis by Reducing Oxidative Stress, Inflammation, and Apoptosis through Inhibition of TLR4/MAPKs/NF‐κB Pathway

SCOPE: 6-Gingerol is one of the primary pungent constituents of ginger. While 6-gingerol has many pharmacological effects, its benefits for myocardial fibrosis, including its exact role and underlying mechanisms, remain largely unexplored. The present study is designed to characterize the cardio-protective effects of 6-gingerol in myocardial fibrosis mice and possible underlying mechanisms. METHODS AND RESULTS: ) for 14 days. Pathological alterations, fibrosis, oxidative stress, inflammation response, and apoptosis are examined. In ISO-induced myocardial fibrosis, 6-gingerol treatment decreases the J-point, heart rate, cardiac weight index, left ventricle weight index, creatine kinase (CK), and lactate dehydrogenase serum levels, calcium concentration, reactive oxygen species, malondialdehyde, and glutathione disulfide (GSSG), and increases levels of superoxide dismutase, catalase, glutathione, and GSH/GSSG. Further, 6-gingerol improved ISO-induced morphological pathologies, inhibited inflammation and apoptosis, and suppressed the toll-like receptor-4 (TLR4)/mitogen-activated protein kinases (MAPKs)/nuclear factor κB (NF-κB) signaling pathways. CONCLUSION: The protective effect of 6-gingerol in mice with ISO-induced myocardial fibrosis may be related to the inhibition of oxidative stress, inflammation, and apoptosis, potentially through the TLR4/MAPKs/NF-κB signaling pathway.