Inhibition of mTOR/S6K1/4E-BP1 Signaling by Nutraceutical SIRT1 Modulators

ABSTRACT

The mTOR pathway plays a crucial role in many human diseases, mostly associated with an over hyperactivity of the mTOR signaling, which makes its inhibitors potentially effective therapeutics. Thus, it is important to consider not only the mTOR pathway, but also all those factors that play a key role in its regulation, such as SIRT1 and AMPK. We previously demonstrated the role of some nutraceutical SIRT1 modulators in AMPK and mTOR pathway, showing the presence of a synergistic effect. Now we take further our research by evaluating the effect of berberine, quercetin, tyrosol, and ferulic acid on the mTOR/S6K1/4E-BP1 signaling, along with the existence of any synergistic effect between the following associations: berberine + tyrosol, tyrosol + ferulic acid, ferulic acid + quercetin. Our results indicate the existence of an important relationship between the substances tested and the pathway of mTOR/S6K1/4E-BP1, a report corroborated by the bond of mTOR with SIRT1/AMPK pathways and by their reciprocal regulation.

Acknowledgment

The authors acknowledge Dr.Shivakumar Kolachalam for the extensive proof reading and the revision of the English language, the laboratory staff, and the trainees for their participation and their continued commitment to some experimental phases and especially in the development of some Western blot.

Additional information

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors, but was only funded by home institution funds.