Network pharmacology integrated with experimental verification reveals the antipyretic characteristics and mechanism of Zi Xue powder.

Context: Zi Xue Powder (ZXP) is a traditional formula for the treatment of fever. However, the potential mechanism of action of ZXP remains unknown.

Objective: This study elucidates the antipyretic characteristics of ZXP and the mechanism by which ZXP alleviates fever.

Materials And Methods: The key targets and underlying fever-reducing mechanisms of ZXP were predicted using network pharmacology and molecular docking. The targets of ZXP anti-fever active ingredient were obtained by searching TCMSP, STITCH and HERB. Moreover, male Sprague-Dawley rats were randomly divided into four groups: control, lipopolysaccharide (LPS), ZXP (0.54, 1.08, 2.16 g/kg), and positive control (acetaminophen, 0.045 g/kg); the fever model was established by intraperitoneal LPS injection. After the fever model was established at 0.5 h, the rats were administered treatment by gavage, and the anal temperature changes of each group were observed over 10 h after treatment. After 10 h, ELISA and Western blot analysis were used to further investigate the mechanism of ZXP.

Results: Network pharmacology analysis showed that MAPK was a crucial pathway through which ZXP suppresses fever. The results showed that ZXP (2.16 g/kg) decreased PGE2, CRH, TNF-a, IL-6, and IL-1β levels while increasing AVP level compared to the LPS group. Furthermore, the intervention of ZXP inhibited the activation of MAPK pathway in LPS-induced fever rats.

Conclusions: This study provides new insights into the mechanism by which ZXP reduces fever and provides important information and new research ideas for the discovery of antipyretic compounds from traditional Chinese medicine.