Abstract
Background:
The HuoXueTongFu Formula (HXTF) originates from the classic prescription "DaHuangMuDan Decoction" from the "Synopsis of the golden chamber". Our previous study revealed that HXTF has a positive effect on postoperative peritoneal adhesion (PPA). However, the specific mechanism of HXTF on PPA formation within the time-to-treatment window has not been fully elucidated. This study aimed to determine the critical roles of HXTF as a result of its specific anti-inflammatory and antifibrinolytic activities for PPA treatment.
Methods:
The eight main bioactive components of HXTF were subjected to high-performance liquid chromatography-mass spectrometry. The core targets, critical biological processes, and underlying pathways of HXTF and PPA were identified via a series of network pharmacological methods. The specific anti-inflammatory function in the initial step of PPA formation was validated in peritoneal macrophages (PMs) isolated from PPA mice on Day 3 postsurgery. The potential anti-fibrinolytic activity in the next stage of PPA formation was subsequently explored in PPA mice on Day 7 postsurgery.
Results:
Network pharmacology revealed 160 common targets between HXTF and PPA. Several core targets, i.e., matrix metalloproteinase 9 (MMP9), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor 1 (PAI-1), were annotated as important biological processes (extracellular matrix disassembly and the collagen catabolic process). Validation experiments revealed that HXTF could induce macrophage polarization-mediated anti-inflammatory reactions by increasing the phagocytic capacity of PMs and promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). In addition, HXTF promoted fibrinogenolysis and improved fibrinolytic activity, thereby inhibiting collagen deposition and reducing adhesion development.
Conclusion:
The ameliorative effects of herbal HXTF on PPA formation are attributable to the induction of macrophage polarization-mediated anti-inflammatory reactions in the early stage of PPA formation and the promotion of fibrinogenolysis and fibrinolytic activity in the middle stage of PPA formation. HXTF may be a promising alternative agent for the prevention and treatment of PPA.