Morinda Citrifolia (Noni) Inhibits Hepatic Gluconeogenesis via Increased Phosphorylation of Forkhead Transcription Factor (FoxO1)

Abstract

Renewed interest in traditional medicine prompted us to investigate anti‐diabetic effects of Hawaiian medicinal plant, Morinda Citrifolia (noni) in mice fed high‐fat‐diet (HFD). Preliminary studies indicate that noni juice (NJ) improved glucose metabolism in mice fed HFD. Glucose production is increased in diabetes due to the inability of insulin to suppress gluconeogenesis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Since recent studies indicate that NJ synergistically augment insulin action in diabetic rats, we tested the hypothesis that NJ improves glucose metabolism by modulating gluconeogenesis via FoxO1 phosphorylation. In our studies hypoglycemic properties of NJ were associated with inhibition of hepatic FoxO1 mRNA expression and protein levels with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose‐6‐phosphatase (G6P) were also significantly inhibited in mice fed HFD with NJ. Specificity of NJ‐associated FoxO1 regulation of gluconeogenesis was confirmed by siRNA studies using human hepatoma cells, HepG2. Our data suggests that NJ can offer an economical alternative, specifically for culturally sensitive diabetic individuals or those who cannot afford conventional medicine. [USDA‐CREES, 2004‐34135‐15182; NCCAM, R21AT003719].