Integrated animal experiments and network pharmacology for investigating therapeutic effect of celastrol-loaded liposomes on NAFLD

Background: The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is closely related to the increase of the incidence rate of obesity. Aims: To find out the targets of celastrol on NAFLD with the treatment of celastrol-loaded liposomes (Cel-Lips). Methods: Gene Expression Omnibus (GEO) data were used to compare the expression of differential genes in NAFLD patients with normal individuals. Celastrol was loaded into liposomes to improve its solubility, as well as, achieving a passive targeting effect on the liver to improve the availability, which also could delay the release rate of celastrol to prolong the action time and thus reduce the frequency of administration. Due to rarely reported molecular mechanisms of celastrol, with the help of network pharmacological analysis, the targets of celastrol acting on NAFLD were predictively analyzed. Results: An association between NAFLD and lipid metabolism was detected in GEO data. Cel-Lips significantly alleviated NAFLD in vivo. Through network pharmacology, it was found that most of the action pathways of celastrol were related to lipid metabolism. Conclusion: Celastrol has the potential to treat NAFLD, and its possible targets have been identified through network pharmacological screening, which provides a certain basis for the follow-up researches.