Curcumin analog C1

Curcumin analog C1 specifically binds to TFEB at the N terminus and promotes TFEB nuclear translocation without inhibiting MTOR activity. By activating TFEB, Curcumin analog C1 enhances autophagy and lysosome biogenesis in N2a cells. Curcumin analog C1 (0.2-1 μM) dose-dependently increases the levels of LC3-II and SQSTM1/p62 in N2a cells.^[2]

N2a cells are treated with curcumin (Cur, 10 μM) and Curcumin analog C1 (1 μM) for 12 h. Cells are fixed and stained with TFEB antibody and DAPI for showing the nuclear translocation of endogenous TFEB. N2a cells are incubated with Curcumin analog C1 (1 μM) for 12 h. The protein levels of LC3B-II and SQSTM1/p62 are determined by western blotting. N2a and HeLa cells are treated with Curcumin analog C1 (0.5, 1 μM) or sucrose (100 mM) for 12 h. The protein levels of the autophagy marker (LC3B-II), TFEB, and lysosome markers (LAMP1, CTSD) are determined by western blotting.

The LD⁵⁰ value of Curcumin analog C1 is 175 mg/kg in the acute toxicity assay. Short-term oral administration of Curcumin analog C1 (low dosage 10 mg/kg and high dosage 25 mg/kg; for 24 h) dose-dependently increases the expression of LC3B-II and TFEB in the liver, frontal cortex and striatum of the brain. Chronic administration of Curcumin analog C1 (10 mg/kg; daily; for 21 days) activates TFEB and enhances autophagy in rat brains. ^[2]