Effects of andrographolide on cellular metabolism and mitochondrial function: current evidence and insights into its anticancer mechanisms

Andrographolide, a labdane diterpenoid derived from Andrographis paniculata , has demonstrated anticancer activity across multiple preclinical models. Accumulating evidence indicates that andrographolide acts as a multitarget modulator of signaling and metabolic pathways, including PI3K/Akt, MAPK, and AMPK. Reported effects also include context-dependent modulation of Nrf2 signaling, ROS accumulation, loss of mitochondrial membrane potential, alterations in mitochondrial morphology and dynamics, and activation of apoptosis or ferroptosis. However, most studies demonstrate pathway modulation or downstream mitochondrial consequences rather than direct engagement of a validated mitochondrial molecular target. This review integrates current evidence linking cellular metabolism, mitochondrial dysfunction, and regulated cell death to the anticancer effects of andrographolide, while critically examining tumor selectivity, safety, pharmacokinetic limitations, and the predominantly preclinical nature of the available evidence.