Nutraceutical activators of AMPK/Sirt1 axis inhibit viral production and protect neurons from neurodegenerative events triggered during HSV-1 infection

Herpes simplex virus type-1 (HSV-1) is ubiquitous and is able to establish a
lifelong persistent latent infection in neurons of infected individuals. It has
been estimated that in approximately 70% of the population over 50 years old, the virus enters the brain and infects neurons, and possibly undergoes recurrent
reactivation episodes during lifetime, especially in immunodepressed individuals.
We previously showed that the sensors AMP-dependent kinase (AMPK) and Sirtuin 1 (Sirt1), involved in survival pathways and neuroprotection, were affected during the course of HSV-1 infection. To evaluate if natural activators of the AMPK/Sirt1 axis, such as Resveratrol and Quercetin could reduce viral propagation and/or counteract the effects of neuronal infection, we analyzed progeny virion production, neuronal viability and neurodegenerative events during HSV-1 infection. We found that the activators of AMPK/Sirt1 axis, increased the viability of infected neurons, significantly reduced the viral titer in the supernatant and the expression of viral genes. More importantly, pretreatment of neurons with Resveratrol or Quercetin significantly reduced the levels of
caspase-3 cleaved- and hyperphosphorylated tau associated with HSV-1 infection. These results suggest that activators of the AMPK/Sirt1 axis could be potentially useful in reducing the risk of HSV-1 productive infection in neurons and the cellular damage associated with reactivation episodes.

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Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis.

The polyphenol compound resveratrol is reported to have multiple
functions, including neuroprotection, and no major adverse effects have
been reported. Although the neuroprotective effects have been associated
with sirtuin 1 activation by resveratrol, the mechanisms by which
resveratrol exerts such functions are a matter of controversy. We
examined whether resveratrol can be neuroprotective in two models of
multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and
Theiler's murine encephalomyelitis virus-induced demyelinating disease
(TMEV-IDD). EAE was induced in C57BL/6 mice, which were fed a control
diet or a diet containing resveratrol during either the induction or
effector phase or through the whole course of EAE. SJL/J mice were
infected with TMEV and fed a control diet or a diet containing
resveratrol during the chronic phase of TMEV-IDD. In EAE, all groups of
mice treated with resveratrol had more severe clinical signs than the
control group. In particular, resveratrol treatment during the induction
phase resulted in the most severe EAE, both clinically and
histologically. Similarly, in the viral model, the mice treated with
resveratrol developed significantly more severe TMEV-IDD than the
control group. Thus, surprisingly, the resveratrol treatment
significantly exacerbated demyelination and inflammation without
neuroprotection in the central nervous system in both models. Our
findings indicate that caution should be exercised in potential
therapeutic applications of resveratrol in human inflammatory
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Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network | eLife

Resveratrol has beneficial effects on aging, inflammation and
metabolism, which are thought to result from activation of the lysine
deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated
protein kinase. Here we report that resveratrol acts as a
pathway-selective estrogen receptor-α (ERα) ligand to modulate the
inflammatory response but not cell proliferation. A crystal structure of
the ERα ligand-binding domain (LBD) as a complex with resveratrol
revealed a unique perturbation of the coactivator-binding surface,
consistent with an altered coregulator recruitment profile. Gene
expression analyses revealed significant overlap of TNFα genes modulated
by resveratrol and estradiol. Furthermore, the ability of resveratrol
to suppress interleukin-6 transcription was shown to require ERα and
several ERα coregulators, suggesting that ERα functions as a primary
conduit for resveratrol activity.

See Scripps News Release 

Resveratrol Exacerbates Both Autoimmune and Viral Models of Multiple Sclerosis.

 The polyphenol compound resveratrol is reported to have multiple functions, including neuroprotection, and no major adverse effects have been reported. Although the neuroprotective effects have been associated with sirtuin 1 activation by resveratrol, the mechanisms by which resveratrol exerts such functions are a matter of controversy. We examined whether resveratrol can be neuroprotective in two models of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). EAE was induced in C57BL/6 mice, which were fed a control diet or a diet containing resveratrol during either the induction or effector phase or through the whole course of EAE. SJL/J mice were infected with TMEV and fed a control diet or a diet containing resveratrol during the chronic phase of TMEV-IDD. In EAE, all groups of mice treated with resveratrol had more severe clinical signs than the control group. In particular, resveratrol treatment during the induction phase resulted in the most severe EAE, both clinically and histologically. Similarly, in the viral model, the mice treated with resveratrol developed significantly more severe TMEV-IDD than the control group. Thus, surprisingly, the resveratrol treatment significantly exacerbated demyelination and inflammation without neuroprotection in the central nervous system in both models. Our findings indicate that caution should be exercised in potential therapeutic applications of resveratrol in human inflammatory demyelinating diseases, including multiple sclerosis.

Resveratrol inhibits epstein barr virus lytic cycle in burkitt's lymphoma cells by affecting multiple molecular targets.

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The Science Behind the Hype | Resveratrol in Wine & ChocolateThe New York Academy of Sciences

It is hard to imagine a way to improve the appeal of a glass of red wine and a bar of chocolate; indeed, most people need little incentive to indulge more often. Yet recent research suggests that perhaps we should do just that. A few years ago, resveratrol—a compound found in red wine and dark chocolate—made a splash in the news as an anti-aging wonder. Although resveratrol may offer health benefits and has shown some signs of affecting longevity in laboratory models, research is only in its early stages. Since the media touts a new food as a fountain of youth almost daily, it can be difficult to separate the facts from the sales pitches. To explicate the latest research behind these claims, The Sackler Institute for Nutrition Science and Science & the City presented a seminar titled The Science Behind the Hype: Resveratrol in Wine & Chocolate on June 5, 2012. Joseph Baur, a biomedical research scientist at the University of Pennsylvania, described his research into resveratrol's action and explained studies that indicate some promising results, from improved cardiovascular health to alleviated diabetic symptoms. The seminar also delved into the practical applications of this research—how to choose the best glass of wine—with a presentation of local wines by Nick Venditti from Frankly Wines.