Targeting MAPK-ERK/JNK pathway: A potential intervention mechanism of myocardial fibrosis in heart failure

Myocardial fibrosis is a significant pathological basis of heart failure. Overactivation of the ERK1/2 and JNK1/2 signaling pathways of MAPK family members synergistically promotes the proliferation of myocardial fibroblasts and accelerates the development of myocardial fibrosis. In addition to some small molecule inhibitors and Western drugs, many Chinese medicines can also inhibit the activity of ERK1/2 and JNK1/2, thus slowing down the development of myocardial fibrosis, and are generally safe and effective. However, the specific biological mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis still need to be fully understood, and there is no systematic review of existing drugs and methods to inhibit them from improving myocardial fibrosis. This study aims to summarize the roles and cross-linking mechanisms of ERK1/2 and JNK1/2 signaling pathways in myocardial fibrosis and to systematically sort out the small-molecule inhibitors, Western drugs, traditional Chinese medicines, and non-pharmacological therapies that inhibit ERK1/2 and JNK1/2 to alleviate myocardial fibrosis. In the future, we hope to conduct more in-depth research from the perspective of precision-targeted therapy, using this as a basis for developing new drugs that provide new perspectives on the prevention and treatment of heart failure. [Display omitted] •Overactivation of the MAPK-ERK/JNK pathway promotes abnormal proliferation of cardiac fibroblasts and myocardial fibrosis, thereby exacerbating heart failure.•It is crucial to conduct in-depth research on the specific mechanisms of the MAPK-ERK/JNK pathway in myocardial fibrosis.•Precision-targeted therapy represents the future research trend and is expected to provide new drugs for heart failure by inhibiting the MAPK-ERK/JNK pathway.•In addition to small molecule inhibitors and Western medicine, Chinese medicine also suppress the activity of ERK1/2 and JNK1/2 to slow down myocardial fibrosis.•A comprehensive review of various methods for inhibiting ERK1/2 and JNK1/2 will provide a reference for clinical practice in myocardial fibrosis.