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From network prediction to in vivo validation: luteolin attenuates cholestatic liver injury in association with
Yuxin Wu1,2, Shiji Gong3,4, Xin Wu3,4
1Department of General Surgery, Baotou Central Hospital, Baotou, 014040, Inner Mongolia Autonomous Region, China.
Abstract:
Cholestatic liver disease (CLD) is characterized by inflammatory amplification, hepatic stellate cell activation and collagen deposition. Luteolin is a natural flavonoid with reported anti-inflammatory and anti-fibrotic activities. Here, network pharmacology, molecular docking and experimental analyses were integrated to examine the effects of luteolin in CLD, with a focus on PI3K/Akt/GSK-3β-associated signalling. Target prediction identified 181 putative luteolin targets and 4,403 CLD-related targets, with 88 overlapping genes. In a bile duct ligation (BDL) rat model, luteolin treatment was associated with lower serum injury indices, reduced histopathological damage, decreased collagen deposition and lower fibrosis-related readouts. Experimental analyses further showed that luteolin treatment was accompanied by lower phosphorylation-associated readouts along the PI3K/Akt/GSK-3β axis. Together, these findings support an association between luteolin treatment and attenuation of cholestatic liver injury and fibrosis, within a multi-target signalling context that includes PI3K/Akt/GSK-3β.
