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Animal studies have shown that high-dose CUR, particularly when delivered via nanoparticles, can induce tissue toxicity through inflammation-mediated injury (62, 63)

In contrast, sustained or excessive ROS accumulation suppresses AMPK activity by destabilizing the AMPK-LKB1 complex, inducing inhibitory Ser485/491 phosphorylation via Akt/PKA signaling, and causing irreversible oxidative modifications of key cysteine residues (Yan et al., 2022)

At 0.5%, suppression begins to fail within 7-14 days