Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

Ferulic acid, a bacterial metabolite of anthocyanins, seems
likely to be a primary mediator of the health benefits
associated with anthocyanin-rich
diets, and has long been
employed in Chinese cardiovascular medicine. In rodent
studies, it has exerted wide-ranging
antioxidant and
anti-inflammatory
effects, the molecular basis of which
remains rather obscure. However, recent studies indicate
that physiologically relevant concentrations of ferulic
acid can boost expression of Sirt1 at mRNA and protein
levels in a range of tissues. Sirt1, a class III deacetylase,
functions to detect a paucity of oxidisable substrate,
and in response works in various ways to promote
cellular survival and healthful longevity. Sirt1 promotes
‘cell cleansing’ and cell survival by boosting autophagy,
mitophagy, mitochondrial biogenesis, phase 2 induction
of antioxidant enzymes via Nrf2, and DNA repair—while
inhibiting NF-kB-
driven
inflammation, apoptosis, and
cellular senescence, and boosting endothelial expression
of the protective transcription factor kruppel-like
factor 2.
A deficit of the latter appears to mediate the endothelial
toxicity of the SARS-CoV-
2
spike protein. Ferulic acid
also enhances the activation of AMP-activated
kinase
(AMPK) by increasing expression and activity of its
activating kinase LKB1—whereas AMPK in turn amplifies
Sirt1 activity by promoting induction of nicotinamide
phosphoribosyltranferase, rate-limiting
for generation of
Sirt1’s obligate substrate NAD+. Curiously, AMPK acts by
independent mechanisms to potentiate many of the effects
mediated by Sirt1. Hence, it is proposed that ferulic acid
may exert complementary or synergistic health-promoting
effects when used in conjunction with clinically useful
AMPK activators, such as the nutraceutical berberine.
Additional nutraceuticals which might have potential
for amplifying certain protective effects of ferulic acid/
berberine are also discussed.