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In addition, we analyzed the upstream regulation and found puerarin induced Nrf2 activity; cooperation between Nrf2 and ATF4 facilitated the puerarin effects. PERK phosphorylation was detected to be increased by puerarin, while PERK inhibition reduced cellular Trx1, TrxR1, nuclear Nrf2 and ATF4. Altogether, puerarin modulates PERK/Nrf2 that coordinates with ATF4 to active Trx1, which causes SR-A and Lox-1 reduction and lipid uptake inhibition in macrophages. This suggests Trx1 could be an effective target by puerarin in the prevention o
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