Metabolic effects of ginger are chronodependent in a murine model

Ginger is a potential adjunct therapy for dyslipidemia, but the chronopharmacological evidence is limited. This study systematically evaluated the metabolic and oxidative stress impacts of a highly concentrated ginger extract administered at different circadian phases in mice. By continuous oral administration during the active period (Dark onset, Zeitgeber Time 12, ZT12) and rest period (Light onset, Zeitgeber Time 0, ZT0), we monitored time-dependent effects on body weight, glucose homeostasis, lipid profiles, and reactive oxygen species (ROS) levels in serum and vital organs. We also undertook organ-level analysis to reveal tissue-specific circadian patterns in antioxidant responses. ZT0 ginger administration promoted weight gain, while ZT12 administration significantly reduced random blood glucose and total cholesterol levels. Although ginger universally improved lipoprotein profiles (reducing low-density lipoprotein cholesterol and elevating high-density lipoprotein cholesterol) and suppressed serum ROS regardless of timing, these benefits were consistently enhanced by ZT12 administration. Integrated network pharmacology then identified 107 overlapping targets between ginger's active components and circadian rhythm regulators, with pathway enrichment analysis revealing signaling cascades mainly pertaining to lipid metabolism, followed by oxidative stress and glucose metabolism pathways. These findings substantiate the effect of dose timing on both function and organ specificity, providing a mechanistic basis to study ginger as a useful adjunct therapy for dyslipidemia and, more broadly, for optimizing its use in metabolic health management.