AICAR

AICAR (5-aminoimidazole-4-carboxamide riboside) is an AMP-activated protein kinase (AMPK) activator that primarily stimulates AMPK activity by mimicking AMP, thereby regulating metabolic processes. Its core mechanism of action is as follows:

Metabolic Regulation
AICAR promotes insulin-independent glucose uptake by activating AMPK, inhibiting inflammatory cytokines (such as TNF-α and IL-1β) and autophagy-related pathways. In vitro, concentrations of 0.1-1.0 mM inhibited insulin receptor expression in HepG2 cells in a dose-dependent manner. In animal studies, continuous administration of 0.5 mg/g for 14 days improved skeletal muscle metabolic abnormalities in obese mice.

Neuroprotection
In transient cerebral ischemia/reperfusion experiments in aged mice, AICAR significantly reduced neurobehavioral scores, decreased the apoptosis rate in the hippocampal CA1 region, and reduced the expression of apoptosis-related proteins (such as caspase-3 and Bax), while upregulating p-AMPKα expression.

Stem Cell Regulation
AICAR works synergistically with leukemia inhibitory factor (LIF) to maintain embryonic stem cell (ES) cell morphology, upregulate stem cell marker gene expression, and enhance alkaline phosphatase activity. This mechanism may be related to inducing a state of energy stress, but the specific mechanism of action requires further investigation.

Potential Applications
AICAR has been applied to research in areas such as diabetes, obesity, and stem cell differentiation, but its clinical application requires further validation in specific disease models.