Lihui Wang,1 Lina Feng,2 Baicheng Ning,3 Zhuolin Wang,1 Chunmei Dai,4 Mingquan Li2 

1College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 2Department of Neurology, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 3College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China; 4Hospital Management Office, Changchun University of Chinese Medicine, Changchun, Jilin Province, People’s Republic of China

Correspondence: Chunmei Dai, Hospital Management Office, Changchun University of Chinese Medicine, Boshuo Road, Changchun, Jilin, 130117, People’s Republic of China, Tel +86 15843086384, Email 295380009@qq.com Mingquan Li, The Third Affiliated Clinical Hospital of the Changchun University of Chinese Medicine, Boshuo Road, Changchun, Jilin, 130117, People’s Republic of China, Tel +86 15948000577, Email limingquan0001@126.com

Abstract: This review summarizes recent advances in leveraging natural products from Chinese medicine to modulate the nuclear factor kappa B (NF-κB) signaling pathway for the prevention and treatment of neurodegenerative diseases (NDDs), focusing specifically on Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic lateral sclerosis (ALS). NF-κB proteins regulate cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. Emerging evidence indicates that NF-κB plays a pivotal role in driving key hallmarks of NDD progression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and dysregulation of the cell cycle. Natural products from Chinese medicine exert modulatory effects on NF-κB signaling through diverse pharmacological mechanisms, ultimately improving cognitive and motor impairments in preclinical NDDs models. The pleiotropic nature of natural products derived from traditional Chinese medicine (TCM)—which operate through subunit-specific modulation of NF-κB—underscores their potential as next-generation therapeutics. Investigating the intricate regulation of NF-κB by natural products from Chinese medicine will not only enrich our understanding of the pathogenesis of NDDs but also establish a theoretical foundation for the development of new therapeutic drugs for NDDs, providing innovative strategies for prevention and treatment.

Keywords: Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, neuroinflammation, oxidative stress