Current Perspectives on the NF-κB Signaling Axis as a Potential Pharmacological Target in Cardiorenal Syndrome

Qian Liu,1 Xinting Wang,1 Peipei Cheng,1 Tianshu Yang,2 Chen Wang,3,4 Hua Zhou1 1Institute of Cardiovascular Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, 200071, People’s Republic of China; 3Institute of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4TCM Institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Hua Zhou, Email [email protected] Chen Wang, Email [email protected]: Cardiorenal syndrome (CRS) is a disease involving two vital organs, the heart and the kidney, which has been increasingly recognized in recent years. The treatment of CRS is highly challenging due to its complex nature, rapid progression, poor prognosis, and high mortality rate. As a protein complex, nuclear factor kappa-B (NF-κB) regulates the transcription of target genes by entering the nucleus and affects cardiac and renal functions through its involvement in inflammatory reactions and oxidative stress. By evaluating established preclinical and clinical research on CRS to date, we explored the potential of NF-κB inhibition to exert unique cardiorenal protective effects as a novel treatment for CRS. In this review, we have synthesized recent advances in the structure and function of NF-κB within the cardiovascular and renal systems, and explored the mechanistic involvement of NF-κB in CRS. Innovatively, we have identified natural compounds that dually inhibit NF-κB activity in both cardiac and renal tissues, thereby conferring concurrent protection to both organs. Furthermore, we discuss the translational potential and clinical applicability of NF-κB-targeted pharmacology, which may provide critical insights for developing novel therapeutics against CRS.Keywords: cardiorenal syndrome, NF-κB, natural compounds, inflammation, oxidative stress