Deciphering the Pharmacological Mechanism of Compound Purpura Decoction in Treating Henoch‐Schonlein Purpura by Network Pharmacology, Molecular Docking and Experimental Validation

Henoch-Schonlein purpura (HSP) is an immunoglobulin A (IgA)-mediated systemic vasculitis that frequently develops in children and may progress to serious complications. Compound purpura decoction (CPD), a classical herbal combination, exerts favourable effects on the clinical symptoms and prognosis of HSP; however, the underlying molecular mechanism remains unclear. First, high-performance liquid chromatography analysis identified five bioactive components in CPD, including protocatechuic acid, chlorogenic acid, mangiferin, baicalin and buddleoside, with contents of 0.011 ± 0.02, 0.577 ± 0.33, 0.150 ± 0.05, 1.132 ± 0.23 and 0.369 ± 0.23 mg/g, respectively. Additionally, we established an animal model of allergic purpura to evaluate the therapeutic effects of CPD on HSP. CPD effectively alleviated renal and cutaneous vasculitis and reduced IgA deposition. CPD could regulate the Treg/Th17 cell balance, decrease the levels of the proinflammatory factors interleukin-6 and tumour necrosis factor-α, and suppress the expression of C3 and C5 (p < 0.05). Network pharmacology analysis suggested that the mechanism of CPD in HSP treatment mainly involved epidermal growth factor receptor (EGFR)-related targets and pathways, followed by molecular docking confirming strong binding affinity between EGFR and the bioactive components (binding energy< -4.25 kcal/mol). Real-time quantitative polymerase chain reaction and western blot showed that CPD suppressed the activation of the EGFR/extracellular signal-regulated kinase (ERK) signalling pathway (p < 0.05), which could be associated with the inhibition of complement system activation. This study provides a new perspective for understanding the pathogenesis and treatment of HSP.