Integrated Clinical and Network Pharmacology Study Reveals the Efficacy and Multi-Target Mechanism of Shenfu Injection in Septic Shock

Background The high mortality of septic shock demands novel adjunctive therapies. Shenfu Injection (SFI), a traditional Chinese medicine, shows potential but its mechanism remains unclear. Method s We conducted an open-label, randomized trial in 80 patients with septic shock. Patients received standard care with or without adjunctive SFI for 7 days. The primary outcome was 28-day mortality. Key secondary outcomes included inflammatory markers, lactate clearance, and vasopressor duration. Concurrently, network pharmacology analyzed SFIs bioactive components, predicted targets, and enriched pathways, with validation by molecular docking. Results The 28-day mortality was significantly lower in the SFI group (20.0% vs. 42.5%, P=0.030). SFI accelerated clinical improvement, evidenced by greater reductions in IL-6 and procalcitonin, higher 6-hour lactate clearance (35.2% vs. 18.5%, P<0.001), shorter vasopressor duration (48 vs. 72 hours, P<0.001), and more rapid SOFA score decline. Network pharmacology identified 145 SFI-septic shock common targets, with IL-6, SRC, and MAPK3 as central hubs. Pathway analysis revealed significant enrichment in TNF, PI3K-Akt, and IL-17 signaling pathways. Molecular docking confirmed strong binding of key SFI components (e.g., Ginsenoside Rh2) to core targets like IL-6. Conclusion s Adjunctive Shenfu Injection reduces mortality and improves clinical recovery in septic shock, potentially through a multi-target mechanism involving modulation of inflammatory and cellular signaling pathways. This integrative study provides both clinical evidence and a mechanistic framework supporting SFI's use. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020435.