Therapeutic Potential of Berberine in Obesity-Associated Neuroinflammation Through Shared Molecular Pathways: TLR4/NF-κB/MAPK, ROS/NRF2 and NLRP3

Abstract

Obesity is recognized as a pathological condition that induces chronic low-grade systemic inflammation capable of affecting multiple organs, including the central nervous system, thereby promoting neuroinflammation. Although adipose and neural tissues differ in their structural and functional characteristics, they share common inflammatory mechanisms involving the TLR4/NF-κB/MAPK signaling pathways, the ROS/NRF2 axis, and the NLRP3 inflammasome. This review summarizes current evidence demonstrating the ability of berberine (BBR) to modulate these shared molecular pathways across different experimental models and pathophysiological conditions, with particular emphasis on obesity-induced neuroinflammation. A narrative literature search was conducted using academic search and indexing resources, including PubMed, Scopus, Web of Science, and Google Scholar, with the literature updated through 24 August 2026. The available evidence indicates that BBR modulates these signaling pathways, reduces the production of pro-inflammatory cytokines, attenuates oxidative stress, and limits glial activation. Furthermore, several studies suggest that BBR may help preserve the functional integrity of the blood–brain barrier and reduce neuronal damage associated with neuroinflammatory processes. Available evidence suggests that BBR may modulate inflammatory and oxidative pathways involved in obesity-associated neuroinflammation; however, current findings derive mainly from preclinical studies and indirect models. Future studies are needed to determine the bioavailability, central nervous system penetration, and clinical relevance of BBR.