The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

Abstract

A previous report indicated that the flavonoid‐rich extract of bergamot juice (BJe) exerts an anti‐inflammatory effect through the activation of SIRT1 in leukemic monocytes THP‐1 exposed to lipopolysaccharide (LPS). In this study, we deeply investigate the mode of action of BJe, along with its major flavonoids on SIRT1 through cell‐free, in silico, and in vitro experimental models. In the cell‐free assay, all the tested compounds as well as the whole BJe inhibited the deacetylase activity of SIRT1. This finding was reinforced by the results of the in silico study. In THP‐1 cells exposed to LPS, a reduction of SIRT1 activity was observed, effect that was reverted by the pre‐incubation with either BJe or its major flavonoids. This effect was also observed at gene level. Employing an activator and an inhibitor of AMP‐activated protein kinase (AMPK; AICAR and dorsomorphin, respectively), we discovered its involvement in the activation of SIRT1 elicited by BJe or its major flavonoids in whole cell. Our study indicates the dual role of BJe and its components, depending on the employed experimental model as well as reveals their mode of action on the AMPK/SIRT1 axis, suggesting their role as promising candidates in pathologies in which this axis is implied.

A Flavonoid-Rich Extract from Bergamot Juice, Alone or in Association with Curcumin and Resveratrol, Shows Protective Effects in a Murine Model of Cadmium-Induced Testicular Injury

“…Recently, bergamot juice (BJ), obtained from the endocarp of Citrus bergamia Risso et Poiteau (bergamot) fruits, gained the attention of pharmaceutical companies interested in natural products and antioxidant bioactive compounds from dietary sources [ 35 , 36 , 37 ]. Indeed, it has been shown that BJ and its flavonoid-rich fraction (BJe) exert hypolipemic and hypoglycemic activity [ 38 ], and anticancer [ 39 ], anti-infective [ 40 , 41 ], neuroprotective [ 42 ], antioxidant, and anti-inflammatory effects [ 43 , 44 , 45 , 46 ]. However, no data are currently available on the potential role of BJe during Cd challenge.…”

Zebrafish as a Useful Model to Study Oxidative Stress-Linked Disorders: Focus on Flavonoids

“…The capability of these natural compounds to improve health status was attributed especially to their antioxidant activity, being able to prevent and scavenge the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), representing important hallmarks of inflammation [ 20 , 21 , 22 ]. Furthermore, they can influence cellular function by direct interaction with several receptors, as well as modulate intracellular signaling and transcription of gene involved in different pro-inflammatory pathways [ 23 , 24 ]. Flavonoids act as antioxidants through different mechanisms: (i) by scavenging free radicals; (ii) by chelating metallic ions that in turn could have catalyzed the generation of free radicals; (iii) by the donation of a proton from the phenolic compounds to the radicals; (iv) by inhibiting pro-oxidant enzymes, such as lipoxygenases, cyclooxygenases and xanthine oxidases, that generate free radicals; (v) by interfering with the oxidative/antioxidative potential of the cell [ 25 ].…”

Neuroprotective Effect of Bergamot Juice in 6-OHDA-Induced SH-SY5Y Cell Death, an In Vitro Model of Parkinson’s Disease

“…We further demonstrated the antimicrobial effect of BJe [41], as well as its anti-cancer properties, both in vitro [24,25,42] and in vivo [26,43]. On the other hand, the beneficial effects of Citrus fruits and their juice against degenerative conditions are well-known [10,13,37,[44][45][46][47][48].…”

“…Recently, we demonstrated that BJ, along with its flavonoid-rich extract (BJe), possesses antioxidant [27,35] and anti-inflammatory [33,[36][37][38][39][40] activities. We further demonstrated the antimicrobial effect of BJe [41], as well as its anti-cancer properties, both in vitro [24,25,42] and in vivo [26,43].…”