INTRODUCTION: The aqueous extract preparation of Houttuynia cordata, known as H. cordata injection (HCI), is frequently utilized for its antibacterial infection, i.e., Pseudomonas aeruginosa infection. Nevertheless, the precise anti-infective mechanism of HCI remains unclear. Here, we aim to elucidate the mechanism by which HCI combats pulmonary infection caused by P. aeruginosa. METHODS: The models of P. aeruginosa biofilm formation, murine acute lung infection, and macrophage cell co-culture caused by P. aeruginosa were established to evaluate the mechanism of HCI intervention in vivo and in vitro. RESULTS: First, this study found that HCI modestly inhibits P. aeruginosa growth in vitro but effectively suppresses virulence factors. In vivo, HCI showed therapeutic efficacy in murine acute lung infection and Galleria mellonella infection models by reducing bacterial load, protecting lung tissue, and suppressing inflammation. Network pharmacology suggested the TLR4 and NF- κB pathways are important in HCI's action against P. aeruginosa pneumonia. Mechanistically, early HCI exposure induced LPS release from bacteria, promoted M1 macrophage polarization, enhanced secretion of effector molecules, upregulated TLR4/MyD88/NF-κB signaling, and increased bacterial phagocytosis in Raw264.7 and THP-1 cells. Interestingly, prolonged HCI treatment inhibited LPS-induced TLR4/MyD88/NF-κB activation and prevented excessive proinflammatory cytokine release. DISCUSSION: HCI might exhibit inhibitory effects on acute pulmonary infection of P. aeruginosa by TLR4/MyD88/NF-κB pathway activation, thereby modulating macrophage M1 polarization for efficient phagocytosis, and eventually HCI can also alleviate the excess inflammatory damage. CONCLUSION: The presented results imply that the possible bidirectional pharmacological effects of HCI should be key to the anti-infection mechanism of HCI.
Wang et al. (Mon,) studied this question.