There have been intense research interests in sirtuins since the establishment
of their regulatory roles in a myriad of pathological processes. In the last two decades,
many research efforts have been dedicated to the development of sirtuin modulators. Although
synthetic sirtuin modulators are the focus, natural modulators remain an integral
part to be further explored in this area as they are found to possess therapeutic potential
in various diseases, including cancers, neurodegenerative diseases, and metabolic disorders.
Owing to the importance of this cluster of compounds, this review gives a current
stand on the naturally occurring sirtuin modulators, associated molecular mechanisms,
and their therapeutic benefits. Furthermore, comprehensive data mining resulted in detailed
statistical data analysis pertaining to the developmental trend of sirtuin modulators
from 2010-2020. Lastly, the challenges and future prospects of natural sirtuin modulators
in drug discovery will also be discussed.