Alisol B decreased CD36 expression and attenuated hepatocyte lipid accumulation and lipotoxicity via regulating RARα-HNF4α-PPARγ cascade. (A) HEK293 cells were transient transfected and then treated with Alisol B. The agonistic activity on RARα was detected in luciferase reporter assay. (B) The gene expression of RARα was detected. (C) The mRNA levels of RARα, HNF4α, PPARγ, and CD36 were measured in hepatocytes treated with Alisol B (10 μM). (D–G) Primary hepatocytes were transfected with RARα siRNA for 24 h and then treated with Alisol B (10 μM). (D) The mRNA levels of RARα, HNF4α, PPARγ, and CD36; (E) BODIPY-C16 fluorescence (600× magnification); (F) cellular TG; and (G) cellular ROS were detected. (H–K) Primary hepatocytes were overexpressed with RARα via transient plasmid transfection for 24 h. (H) The mRNA levels of RARα, HNF4α, PPARγ, and CD36; (I) BODIPY-C16 fluorescence (600× magnification); (J) cellular TG; and (K) cellular ROS were conducted. Data are expressed as mean ± SD, n = 5. In (F,G,J,K), ## p < 0.01 compared with normal control group; * p < 0.05, ** p < 0.01 compared with the PA-induced group. In the other figures, * p < 0.05, ** p < 0.01 compared with the normal control group.