Molecular networking-based GC/MS profiling of Citrus japonica Thunb. peel and pulp lipophilic fractions and their antimicrobial potential against diabetic foot ulcer pathogens.

Diabetic ulcers are a serious complication of diabetes, often exacerbated by microbial infections that hinder wound healing. This study investigates the antimicrobial potential of non-polar constituents derived from the peel and pulp of Citrus japonica (kumquat) as natural antimicrobial agents for managing microbial infections associated with diabetic ulcers. Gas Chromatography-Mass Spectrometry (GC-MS)-based molecular networking enriches the annotation of 113 and 92 compounds in the peel and pulp lipophilic fractions, respectively. Moreover, preliminary in vitro antimicrobial assays demonstrated that the pulp non-polar extract possesses weak to moderate efficacy against common diabetic ulcer pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans, with inhibition zone diameters (mm) of 13.67 ± 0.89, 19.33 ± 0.22 and 20.5 ± 0.17 compared to those of the standard 12.33 ± 0.22, 19.83 ± 0.39 and 10.71 ± 0.05 as well as MIC values (mg/mL) of 3.75 ± 0.04, 0.938 ± 0.002 and 1.88 ± 0.001, respectively. Furthermore, Principal Component Analysis (PCA)-based GC-MS revealed notable variations in the chemical profiles of the peel and pulp lipophilic fractions, with the pulp showing higher concentrations of trimethyl citrate and azelaic acid ester, compounds related to antibacterial and antifungal properties. This finding suggests that non-polar matter, especially from the pulp, could be a promising natural antimicrobial agent for treating diabetic ulcers. Further research is required to assess its efficacy in clinical applications and to explore its mechanisms of action in promoting wound healing and preventing infections.