Synergistic sleep-promoting effects of magnesium and apigenin in normal and insomnia mouse models

Insomnia is a prevalent condition affecting sleep quality and overall health. While apigenin and magnesium individually exhibit sleep-promoting properties, their combined potential remains unexplored. This study investigates the combinatory effects of apigenin and magnesium (A + M) on sleep. Results demonstrated that A + M significantly enhanced sleep duration in normal mice (44%, p < 0.005), caffeine-induced sleep disturbed mice (32%, p < 0.001), and p-chlorophenylalanine (PCPA)-induced insomnia mice (37%, p < 0.05), surpassing individual treatments of apigenin or magnesium. Mechanistically, A + M treatment suppressed systemic and hypothalamic TNFα levels in PCPA-induced mice. We further demonstrated A + M treatment could inhibit microglial activation, potentially via suppressing NFκB signaling. These findings demonstrate the combinatory efficacy of A + M in restoring sleep architecture and suggest its potential as a natural, effective intervention for insomnia management.