Black tea polyphenols mimic insulin/insulin‐like growth factor‐1 signalling to the longevity factor FOXO1a

Abstract

SummaryIn vertebrates and invertebrates, relationships between diet and health are controlled by a conserved signalling pathway responsive to insulin-like ligands. In invertebrate models for example, forkhead transcription factor family O (FOXO) transcription factors in this pathway regulate the rate of aging in response to dietary cues, and in vertebrates, obesity and age-induced deficits in the same pathway are thought to contribute to dysregulation of hepatic gluconeogenesis through genes such as phosphoenolpyruvate carboxykinase (PEPCK). Recently, we have begun to screen for dietary constituents capable of regulating this pathway in our cell culture model. Here, we identify three black tea theaflavins, theaflavin 3-Ogallate, theaflavin 3′ ′ ′ ′ -O -gallate, theaflavin 3,3′ ′ ′ ′ di-O -gallate and thearubigins as novel mimics of insulin/IGF-1 action on mammalian FOXO1a, PEPCK and moreover we provide evidence that the effects on this pathway of the green tea constituent (-)-epigallocatechin gallate depend on its ability to be converted into these larger structures. With the exception of water, tea is the most popular drink globally, but despite this, little is known about the biological availability of black tea polyphenols in vivo or the molecular target(s) mediating the effects presented here. Further investigation in these two areas might provide insight into how age-related metabolic disease may be deferred.

Delphinidin-Rich Maqui Berry Extract (Delphinol®) Lowers Fasting and Postprandial Glycemia and Insulinemia in Prediabetic Individuals during Oral Glucose Tolerance Tests

“…These possible mechanisms are in line with the results of Rojo et al [18], which describe insulin-like effects in liver and muscle cells of delphinidin 3-sambubioside 5-glucoside, one of the main anthocyanins of maqui berry, and identify this particular purified anthocyanin as, at least partially, responsible of the antidiabetic effects. However, in the present work, we cannot rule out that other polyphenol components of Delphinol could also be synergetically having insulin-like effects, as described, for example, by Cameron et al [20]. We can discard inhibition of β -glucosidases, in our particular case, as we used pure glucose as the OGTT challenge.…”

Oral hypoglycaemic, antihyperglycaemic and antidiabetic activities of Sri Lankan Broken Orange Pekoe Fannings (BOPF) grade black tea (Camellia sinensis L.) in rats

“…This suggests insulinomimetic activity of BTI. Indeed, the polyphenols in black tea such as theaflavins, theaflavin 3-O-gallate, theaflavin 3 -O-gallate, theaflavin 3,3 -di-O-gallate and thearubigins are shown to posses insulinomimetic activity (Cameron et al, 2008). Interestingly, some of traditional practitioners in diabetes treatments use plant extracts having the action of insulinomimetic action (Purello et al, 1983).…”

Neurohormetic phytochemicals: An evolutionary–bioenergetic perspective

“…FOXO is suggested to be involved in age-related neurodegenerative diseases including AD (Manolopoulos et al, 2010). In rat and human cell lines, three black tea theaflavins, namely theaflavin 3- O -gallate, theaflavin 3′- O -gallate and theaflavin 3,3′di- O -gallate, and thearubigins were identified as insulin/IGF-1 action mimetics on mammalian FOXO1a (Cameron et al, 2008). Administration of the carotenoid lycopene to rats ameliorated insulin signaling deficits and improved cognitive function in rats (Yin et al, 2014).…”