Identification of active ingredients from Lamiophlomis rotata that increase wound repair in mouse skin

Background and Purpose We previously showed that the iridoid glycoside extract of Lamiophlomis rotata (IGLR) induces M2 macrophage polarisation to accelerate wound healing. The potentially active compounds (quality markers) in IGLR that accelerate wound healing have not been elucidated; we here identified quality markers that accelerate wound healing. Experimental Approach After IGLR gavage of dorsal excisional wound mice and normal mice for 7 days, the tissues were analysed using the matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry imaging (MSI) method and were further validated by liquid chromatography/mass spectrometry (LC/MS) coupled with multivariate analyses to identify quality markers. Key Results Using the MSI assay, Shanzhiside methyl ester (SM), 8- O -acetylshanzhiside methyl ester (ASM) and Phlorigidoside C (PhC) were identified as the quality markers in IGLR and overlapped with endogenous metabolites (lactate, citrate and itaconate) in the same class by UMAP manifold analysis. Additionally, the results were also confirmed by UPLC-Q/TOF-MS coupled with multivariate analyses of the skin tissues in normal and wound groups. MSI data from the livers and kidneys revealed that the accumulation of SM, ASM and PhC in the livers significantly increased in the model group, and the ion intensity of their glucuronide conjugates in the kidneys was decreased compared to the normal group. These results suggested that bioavailability of these compounds was improved in the wound group. Conclusions and Implications The overall data demonstrated that SM, ASM and PhC were selectively increased in new granulation tissues, and are most likely the quality markers that accelerate wound healing. Graphical