Houttuynia cordata polysaccharides ameliorate atopic dermatitis in mice through modulation of skin immune barrier and lipid metabolism

Atopic dermatitis (AD), a prevalent inflammatory skin condition, significantly impacts patients' quality of life due to the multifaceted etiology and the lack of targeted therapeutic options. As the “Chinese herbal antibiotic”, Houttuynia cordata is renowned for its diverse pharmacological attributes. This study aims to investigate the therapeutic potential of Houttuynia cordata polysaccharides (HCP) in treating AD and to elucidate the mechanisms involved. HCP alleviated AD in MC903-induced mice by reducing epidermal thickness, skin lesions, mast cell infiltration, inflammatory cytokines, and restoring barrier proteins. It also suppressed inflammatory cytokines/chemokines via the mitogen-activated protein kinase (MAPK) pathway in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and tumor necrosis factor-alpha (TNF-α)/ interferon-γ(IFN-γ)-induced human keratinocytes cells (HaCaT). Moreover, HCP modulated inflammation-related metabolic pathways, especially restored lipid metabolic homeostasis through upregulating phosphatidylcholine (PC) and downregulating triglyceride (TG), lysophosphatidylcholine (LPC), potentially alleviating AD-like lesions and restoring barrier function. Our findings underscore the promising potential of HCP as a topical therapeutic candidate for AD treatment, offering a new direction for the development of targeted AD therapies.