Psoriasis is a refractory inflammatory skin disorder in which keratinocyte hyperproliferation is a crucial pathogenic factor. Up to now, it is commonly acknowledged that
psoriasis has a tight connection with metabolic disorders.
Withanolides from Datura metel L. (DML) have been proved to possess anti-inflammatory and anti-proliferative properties in multiple diseases including
psoriasis.
Withanolide B (WB) is one of the abundant molecular components in DML. However, existing experimental studies regarding the potential effects and mechanisms of WB on
psoriasis still remain lacking. Present study aimed to integrate network pharmacology and untargeted metabolomics strategies to investigate the
therapeutic effects and mechanisms of WB on metabolic disorders in
psoriasis. In our study, we observed that WB might effectively improve the symptoms of
psoriasis and alleviate the epidermal
hyperplasia in
imiquimod (IMQ)-induced
psoriasis-like mice. Both network pharmacology and untargeted metabolomics results suggested that
arachidonic acid metabolism and
arginine and
proline metabolism pathways were linked to the treatment of
psoriasis with WB. Meanwhile, we also found that WB may affect the expression of regulated
enzymes 5-lipoxygenase (5-LOX), 12-LOX,
ornithine decarboxylase 1 (ODC1) and
arginase 1 (ARG1) in the
arachidonic acid metabolism and
arginine and
proline metabolism pathways. In summary, this paper showed the potential metabolic mechanisms of WB against
psoriasis and suggested that WB would have greater potential in
psoriasis treatment.