A Novel Compound DBZ Alleviates Chronic Inflammatory Pain and Anxiety-Like Behaviors by Targeting the JAK2-STAT3 Signaling Pathway.

Abstract

Chronic pain profoundly disrupts patients' daily lives and places a heavy burden on their families. Tanshinol Borneol Ester (DBZ), a novel synthetic derivative, has demonstrated anti-inflammatory and anti-atherosclerotic effects, yet its impact on the central nervous system (CNS) remains largely unexplored. This study systematically examines the CNS effects of DBZ through a combination of in vivo, in vitro, network pharmacology, and molecular docking approaches. In vivo, we utilized a mouse model of chronic inflammation induced by complete Freund's adjuvant (CFA) to evaluate DBZ's influence on pain, anxiety-like behaviors, and its modulation of inflammatory and oxidative stress markers within the anterior cingulate cortex (ACC). In vitro studies on primary mouse astrocytes assessed DBZ's effects on cell viability and inflammatory marker expression. Network pharmacology was employed to elucidate DBZ's potential molecular targets and pathways, While molecular docking provides valuable docking confirmed its interactions with key components of the JAK2-STAT3 signaling pathway. Our findings demonstrate that DBZ effectively mitigates CFA-induced chronic pain and anxiety-like behaviors. It significantly suppresses astrocytes activation, reduces levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, and diminishes oxidative stress markers such as ROS and MDA, while enhancing SOD levels. Moreover, DBZ modulates excitatory synaptic proteins and the JAK2-STAT3 signaling pathway in the ACC, suggesting its role in neuroprotection. These results position DBZ as a promising candidate for the treatment of chronic pain and anxiety, offering a potential foundation for the development of new therapeutic agents.