Thymoquinone exerts anti-inflammatory effects in multiple disease models by regulating immune-inflammatory homeostasis.

Thymoquinone (TQ), an abundant phytochemical identified from Nigella sativa seeds of the Ranunculaceae family, is recognized for its multifaceted biological effects involving inflammatory regulation, oxidative stress control, and immune modulation. This review summarizes the anti-inflammatory effects of TQ across inflammation-related diseases and integrates bibliometric analysis, network pharmacology, and molecular docking approaches to explore its potential cross-disease immunoregulatory mechanisms. Accumulating evidence suggests that TQ may exert immunoregulatory effects through modulation of key inflammatory and antioxidant pathways, including nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase/signal transducer and activator of transcription (JAK/STAT), the NLR family pyrin domain containing 3 (NLRP3) inflammasome, nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1), and peroxisome proliferator-activated receptor gamma (PPARγ), accompanied by changes in pro-inflammatory mediator production, immune cell functions, and tissue responses in various inflammation-related disease models. Cross-disease mechanistic integrative network pharmacology analysis identified recurrent candidate nodes such as AKT1, TNF, and IL6 across different disease-related networks, suggesting that the broad-spectrum anti-inflammatory effects of TQ may involve coordinated modulation of partially shared immune-inflammatory networks, rather than targeting a single pathogenic pathway. Therefore, this review attempts to break away from the conventional summary model organized by individual diseases or single signaling pathways, and instead adopts the perspective of "immune-inflammatory homeostasis regulation" to comprehensively analyze the anti-inflammatory mechanisms of TQ across various diseases. This approach may facilitate a deeper understanding of its broad-spectrum immunomodulatory effects and potentially provide new theoretical insights for the translation of natural active products into precision immunotherapeutic strategies.