Blood glucose lowering effect of Tridax procumbens in type 2 diabetes may be attributed to AMPK activation and suppression of hepatic gluconeogenesis (259.8)

Abstract

Traditional knowledge and anecdotal evidence suggest that Tridax procumbens Linn may have anti‐inflammatory and blood glucose lowering properties. Recent studies have shown that T.procumbens extract was effective in lowering blood glucose (42‐71% blood glucose reduction at 250‐500 mg/kg body weight) in alloxan‐induced diabetic rats. The goals of this study were to evaluate blood glucose lowering potential of T.procumbens extract in subjects with type 2 diabetes and characterize underlying molecular mechanisms. Twenty individuals with established type 2 diabetes were orally administered (15 ml, twice daily) T.procumbens extract, prepared according to Ayurveda guidelines, for a period of 4 weeks. Fasting blood glucose concentrations were reduced by 11% in men and 20% in women, and post‐prandial blood glucose concentrations were decreased by 26% in men and 29% in women. No adverse effects were reported by the participants. Chemical and microbial analyses of T. procumbens extract demonstrated the presence of phenolics, carotenoids, and flavonoids, and absence of microbial contaminants, aflatoxins, and heavy metals. T.procumbens extract demonstrated strong antioxidant potential and anti‐inflammatory activity as evidenced through Trolox equivalent antioxidant capacity, ferric‐ion reducing potential, hydrogen peroxide scavenging activity, and metal ion chelating effect in vitro, and inhibition of NFκB and IkBα in LPS‐stimulated RAW 264.7 murine macrophages. T.procumbens extract significantly increased AMPK activation and suppressed dexamethasone‐induced PEPCK and G6Pase gene expression with subsequent decrease in hepatic glucose production in H4IIE cells. Our studies indicate that T.procumbens extract exhibits strong antioxidant and anti‐inflammatory properties. Activation of AMPK and suppression of hepatic glucose production may be one mechanism that contributes to the glucose‐lowering property of T. procumbens. Grant Funding Source: Diabetes Action Research and Education Foundation

Enhanced phosphorylation of AMPK by lutein and oxidised lutein that lead to mitochondrial biogenesis in hyperglycemic HepG2 cells

“…The increased activation of PGC‐1α in the L and OXL treated HepG2 cells further supports the above observation that activation of PGC‐1α in turn downregulated the PEPCK and G6pase genes . PGC‐1α being a main regulator of mitochondrial biogenesis controls the gluconeogenic pathway by activating AMPK …”

“…The increased activation of PGC-1α in the L and OXL treated HepG2 cells further supports the above observation that activation of PGC-1α in turn downregulated the PEPCK and G6pase genes. 34 PGC-1α being a main regulator of mitochondrial biogenesis controls the gluconeogenic pathway by activating AMPK. 3 In our study L and OXL found to increase the mRNA expression of PGC-1α by 1.4 and 1.9-fold and protein expression by 1.5 and 2.1-fold, respectively, in HepG2 cells.…”