© 2020 PFPC
Resveratrol is a natural compound found in grape seeds and skin and in red wine. Used previously against MERS-CoV infection (Lin et al., 2017).
Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC - "Effective inhibition of MERS-CoV infection by resveratrol" BMC Infect Dis 17(1):144 (2017) doi: 10.1186/s12879-017-2253-8. PMID: 28193191; PMCID: PMC5307780.
Now suggested for treatment in COVID-19.
Magrone T, Magrone M, Jirillo E - "Focus on Receptors for Coronaviruses with Special Reference to Angiotensin-converting Enzyme 2 as a Potential Drug Target - A Perspective" Endocr Metab Immune Disord Drug Targets (2020) doi: 10.2174/1871530320666200427112902. Epub ahead of print. PMID: 32338224."Taken together, these evidences suggest that CoV-induced down-regulation of ACE2 activates RAS with collateral damage to organs, such as lungs, in the course of SARS-related pneumonia. Then, putative therapeutic measures aimed at increasing ACE2 levels on respiratory epithelial cells should be taken into serious consideration. Quite interestingly, over the past few years, three key papers have demonstrated the ability of a polyphenol, resveratrol (RES), to experimentally deactivate the RAS system in maternal and post-weaning high fat diet, arterial ageing and high fat diet, respectively [42-44]. In all these experimental models, RES led to an increase of ACE2 with reduction of organ damage."
Previous studies have shown that resveratrol exerted antiviral activities by blocking the NF-κB pathway (Zhang et al., 2015).
Zhang L, Li Y, Gu Z, Wang Y, Shi M, Ji Y, Sun J, Xu X, Zhang L, Jiang J, et al. - "Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-kappaB signaling pathway" PLoS One 10(2):e0116879 (2015) doi: 10.1371/journal.pone.0116879.
"Resveratrol, the naturally occurring polyphenolic compound characterized by anti-oxidative, anti-inflammatory and apoptotic properties, appears to contribute substantially to cardioprotection and cancer-prevention. In addition, resveratrol is believed to regulate several biological processes, mainly metabolism and aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both papillary and follicular thyroid cancer by activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway as well as increase of p53 and its phosphorylation. Finally, resveratrol also influences thyroid function by enhancing iodide trapping and, by increasing TSH secretion via activation of sirtuins and the phosphatidylinositol- 4-phosphate 5 kinase γ (PIP5Kγ) pathway, positively affects metabolism."
The NF-KappaB pathway is downstream from Gq/11 activation.
"Fluoride-induced Ac-p53 was suppressed by the SIRT1 activator resveratrol (50 µM)."
Suzuki M, Ikeda A, Bartlett JD - " Sirt1 overexpression suppresses fluoride-induced p53 acetylation to alleviate fluoride toxicity in ameloblasts responsible for enamel formation" Arch Toxicol 92(3):1283-1293 (2018) doi: 10.1007/s00204-017-2135-2. Epub 2017 Nov 28. PMID: 29185024; PMCID: PMC6667832.
Zeng XX, Deng J, Xiang J, Dong YT, Cao K, Liu XH, Chen D, Ran LY, Yang Y, Guan ZZ - "Protections against toxicity in the brains of rat with chronic fluorosis and primary neurons exposed to fluoride by resveratrol involves nicotinic acetylcholine receptors" J Trace Elem Med Biol 60:126475 (2020) doi: 10.1016/j.jtemb.2020.126475. Epub 2020 Feb 27. PMID: 32142957.
NOTE: Nicotinic acetylcholine receptors are regulated by TH (Moffet et al., 2019; Leach et al., 2015))
Moffett SX, Klein EA, Brannigan G, Martin JV - "L-3,3',5-triiodothyronine and pregnenolone sulfate inhibit Torpedo nicotinic acetylcholine receptors" PLoS One 14(10):e0223272 (2019) doi: 10.1371/journal.pone.0223272. PMID: 31584962; PMCID: PMC6777777.
Leach PT, Kenney JW, Connor DA, Gould TJ - "Thyroid receptor β involvement in the effects of acute nicotine on hippocampus-dependent memory" Neuropharmacology 93:155-63 (2015) doi: 10.1016/j.neuropharm.2015.01.026. Epub 2015 Feb 7. PMID: 25666034; PMCID: PMC4387063
Zhao Q, Tian Z, Zhou G, Niu Q, Chen J, Li P, Dong L, Xia T, Zhang S, Wang A - "SIRT1-dependent mitochondrial biogenesis supports therapeutic effects of resveratrol against neurodevelopment damage by fluoride" Theranostics 10(11):4822-4838 (2020) doi: 10.7150/thno.42387. PMID: 32308752; PMCID: PMC7163447
Fluoride AND Thyroid
Sarkar C, Pal S - "Ameliorative Effect of Resveratrol Against Fluoride-Induced Alteration of Thyroid Function in Male Wistar Rats" Biol Trace Elem Res (2014) PubMed PMID: 25164033
http://link.springer.com/article/10.100 ... 8-3#page-2
"Resveratrol, via Nrf2, activates phase II antioxidant enzymes, mitigates oxidative stress, normalizes AT1R–G-protein signaling and Na/K-ATPase regulation, and decreases BP in SHR."
Javkhedkar AA, Banday AA - "Antioxidant resveratrol restores renal sodium transport regulation in SHR" Physiol Rep 3(11):e12618 (2015) doi: 10.14814/phy2.12618. Epub 2015 Nov 24. PMID: 26603454; PMCID: PMC4673646.
Carolina BAR, David F d AV, Aline OD, Brian B, Juliano M M - "Anti-Contractile Mechanism of Resveratrol in Non-Vascular
Smooth Muscle Under α1-Adrenoceptor Stimulation involves IP3-Receptor, Protein Kinase-C and NADPH Oxidase" Open Acc J of Toxicol 4(1):
555627 (2019) DOI: 10.19080/OAJT.2019.04.555627
https://juniperpublishers.com/oajt/pdf/ ... 555627.pdf
Duntas LH - "Resveratrol and its impact on aging and thyroid function" J Endocrinol Invest 34(10):788-92 (2011) doi: 10.3275/7926. Epub 2011 Sep 23. PMID: 21946130