Chronic Silymarin, Quercetin and Naringenin Treatments Increase Monoamines Synthesis and Hippocampal Sirt1 Levels Improving Cognition in Aged Rats

Abstract

Polyphenols have beneficial neurological effects delaying cognitive and motor decline in aging due to their antioxidant, antiinflammatory and neuroprotective properties. These effects could be related to SIRT1 activation (implicated in synaptic plasticity, memory and inflammation) and monoaminergic synthesis modulation. In this work, we studied in old male rats, the in vivo effects of long-term administration of different polyphenols (silymarin, quercetin and naringenin; 20 mg/kg/day i.p, 4 weeks) (Sprague-Dawley, 18 months) on cognition and motor coordination. We also analyzed in different brain regions: tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activities, which mediate central monoaminergic neurotransmitters synthesis; and immunoreactivities of SIRT1 and NF-κB (total and acetylated forms). Results indicated that chronic polyphenolic treatments showed restorative effects on cognition and motor coordination consistently with the biochemical and molecular results. Polyphenols reversed the age-induced deficits in monoaminergic neurotransmitters (serotonin, noradrenaline, and dopamine), increasing TPH and TH activity. In addition, polyphenolic treatments increased SIRT1 levels and decreased NF-κB levels in hippocampus. These results confirm polyphenolic treatments as a valuable potential therapeutic strategy for attenuating inflamm-aging and brain function decline.

Quercetin protected against isoniazide‐induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway

“…Caspase‐3 and caspase‐9 are cysteine protease that are involved in mediating cell apoptosis; once activated, they result in cell shrinkage, DNA degradation, and the formation of apoptotic bodies cascade . It has been shown that INH may expedite physiological apoptosis by decreasing the expression of Bcl‐2, elevating Bax, activating caspase‐9 and caspase‐3 in vivo and in vitro . The findings from the present research were consistent with previous reports and further demonstrated that pretreatment with Que reversed these changes in HepG2 cells.…”

“…Quercetin (Que) is a flavonoid compound, ubiquitous in nature, with a variety of biological activities, including antioxidant, scavenging‐free radical, anti‐inflammatory, antitumor, antiapoptosis, and immunosuppressive . Mounting evidence shows that Que could have protective effects on the heart, brain, kidney, liver, and metabolic diseases by targeting the SIRT1 pathway . Besides, research on the regulation of Que on ERK also exists .…”

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

“…Other reports suggested that some of the flavonoids here tested are able to modulate SIRT1, although in other experimental models. NAR treatment was reported to increase SIRT1 expression in both insulin‐resistant L6 myotubes and skeletal muscle of albino Wistar rats (Mutlur Krishnamoorthy & Carani Venkatraman, ) as well as in the hippocampal region of aged rats (Sarubbo et al, ). Oliva and co‐workers demonstrated that the chronic treatment of NRG in ethanol‐fed male Wistar rats increased SIRT1 at both gene and protein level (Oliva et al, ).…”

Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice

“…Recently, the combination of dasatinib and quercetin is reported to extend the lives of older people . Quercetin is an SIRT1 activator . Studies have found that quercetin increases monoamine synthesis in aged rats by activating SIRT1 and improves cognitive function in aged rats .…”