ETHNOPHARMACOLOGICAL RELEVANCE:Linderae Radix (LR) is a traditional Chinese medicine widely used in the clinical treatment of ulcerative colitis (UC). Carbonized Linderae Radix (CLR) is produced by stir-frying of LR. However, the effects of carbonization on its chemical composition and therapeutic efficacy in UC remain unclear.
AIM OF THE STUDY:To compare the chemical composition and therapeutic effects of LR and CLR in dextran sulfate sodium (DSS)-induced UC.
MATERIALS AND METHODS:The chemical profiles of LR and CLR were analyzed by UPLC-Triple-TOF/MS. A 2.5 % DSS-induced UC mouse model was used to assess treatment efficacy. Disease indicators such as DAI scores, colon length, and spleen index were evaluated. Histopathology, AB-PAS staining, immunohistochemistry, and immunofluorescence were employed to assess epithelial integrity, mucus barrier, proliferation, and intestinal stem cells (ISCs). Network pharmacology was performed to explore underlying mechanisms. The above results were verified using molecular docking.
RESULTS:Carbonization significantly altered LR's chemical profile, with the loss of bioactive compounds such as Linderalactone and Norisoboldine, and the emergence of new constituents like Ethyl caffeate. Both LR and CLR improved UC symptoms, preserved tight junctions, protected ISCs, and promoted epithelial proliferation. LR more effectively reduced histological damage and maintained crypt structure and goblet cells. CLR showed superior effects on mucus barrier restoration by upregulating MUC2 expression. Network analysis revealed that CLR targets were mainly enriched in inflammation- and apoptosis-related pathways (MAPK, PI3K-Akt, IL-17), while LR was enriched in regenerative and stemness-related pathways (Wnt, Notch, and JAK-STAT).
CONCLUSION:Carbonization alters the chemical composition and therapeutic focus of LR. LR primarily enhances mucosal regeneration and ISCs activity, while CLR improves the mucus barrier and modulates inflammatory responses.