Liposomal chrysin attenuates hepatic ischaemia-reperfusion injury: possible mechanism via inhibiting NLRP3 inflammasome

ObjectivesThe chrysin has properties of low aqueous solubility, bioavailability and absorption, and its effect on hepatic ischaemia-reperfusion (HIR) remains unclear. Thus, we prepared a liposomal chrysin (LC) and explored its effect and potential mechanism on HIR.MethodsA thin-film dispersion method was used to prepare LC, and a mouse HIR model was used. Mice were pre-treated with LC (100 mg/kg) or placebo by gavage feeding at 16.5 h, 8.5 h, 0.5 h before modelling.ResultsThe average particle sizes, polydispersity index, zeta potential, encapsulation efficiency and drug loading of LC were 129 ± 13.53 nm, 0.265 ± 0.021, −34.46 ± 4.14 mV, 95.03 ± 2.17%, 16.4 ± 0.8%. The concentration of chrysin in plasma and liver tissue by LC administration increased 2.54 times and 1.45 times. LC pre-treatment reduced HIR-induced liver injury and inhibited cell apoptosis. Besides, LC pre-treatment decreased reactive oxygen species and malondialdehyde and inhibited the inflammation response indicated by lower IL-6, TNF-α, infiltration of neutrophils. Further, LC pre-treatment significantly decreased NLRP3 activation, evidenced by reduced cleaved caspase-3, NLRP3, ASC, cleaved caspase-1 and IL-1β expression.ConclusionsLC has good biocompatibility, and it could attenuate HIR-induced injury. Its mechanism was associated with NLRP3 inflammasome inhibition, and LC might be an effective drug for treating and preventing HIR-induced injury.