Silybin ameliorates Pb-induced learning and memory impairment by inhibiting STAT3/hnRNP U/REST and NFκB/hnRNP U

Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.