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. 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. Firstly, HPLC analysis identified five bioactive components in CPD, including protocatechuic acid, chlorogenic acid, mangiferin, baicalin, and buddleoside, with concentrations of 0.011±0.02 mg/g, 0.577±0.33 mg/g, 0.150±0.05 mg/g, 1.132±0.23 mg/g, 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 IL-6 and TNF-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 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 PCR (RT-qPCR) and western blot showed that CPD suppressed the activation of the EGFR/ERK signaling pathway (p<0.05), which could be associated with the inhibition of complement system activation.