Flavonoids: The Innocuous Agents Offering Protection against Alzheimer’s Disease Through Modulation of Proinflammatory and Apoptotic Pathways

Abstract

Background: Beginning from mild cognitive impairment in patients suffering from Alzheimer’s disease (AD), dementia sets in with the progress of the disease. The pathological changes in the brain begin fifteen to twenty years before AD related dementia develops. Presence of senile plaques and neurofibrillary tangles are considered the hallmarks of AD brain. Chronic inflammation resulting from the disruption of equilibrium between anti-inflammatory and pro-inflammatory signalling emerges as another important feature of AD and also other neurodegenerative diseases. Substantial studies demonstrate that this sustained immune response in the brain is associated with neuronal loss, along with facilitation and aggravation of Aβ and NFT pathologies. Although it is well accepted that neuroinflammation and oxidative stress have both detrimental and beneficial influences on the brain tissues, the involvement of microglia and astrocytes in the onset and progress of the neurodegenerative process in AD is becoming increasingly recognized. The cause of neuronal loss, although, is known to be apoptosis, the mechanism of promotion of neuronal death remains undisclosed. Objective: Controlling the activation of the resident immune cells and/or the excessive production of pro-inflammatory and pro-oxidant factors could be effective as therapeutics. Among the phytonutrients, the neuroprotective role of flavonoids is beyond doubt. This review is an exploration of literature on the role of flavonoids in these aspects. Conclusion: Flavonoids are not only effective in ameliorating the adverse consequences of oxidative stress but also impede the development of late onset Alzheimer’s disease by modulating affected signalling pathways and boosting signalling crosstalk.

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

“… In vitro Meroni, Barcellini, Borghi, Vismara, Ferraro, Ciani, Zanussi [11] Lymphocyte Blastogenesis Silybin,0.5, 10, and 25 μM silybin on activating human T lymphocytes and observed that silybin significantly reduce the proliferative reaction to the monoclonal anti-CD3 antibody in a dose-dependent manner In vitro Hawke, Schrieber, Soule, Wen, Smith, Reddy, Wahed, Belle, Afdhal, Navarro, Berman, Liu, Doo, Fried [12] 32 patients with chronic HCV infection Silymarin, 140, 280, 560, or 700 mg clinically meaningful reductions from baseline serum transaminases or HCV RNA titer were observed. Case report Payer et al, 2010 13 A case of an HIV-HCV coinfected patient Administration of silibinin: 20 mg/kg/day for 14 days intravenously Inhibition of HIV replication; a decrease in HCV RNA and HIV RNA Clinical trial Yakoot et al [14] 66 patients with chronic HCV infection Administration of silymarin: 140 mg 3 times daily for 6 months No virological response in the 96.6 % of silymarin treated group Clinical trial Biermer et al [15] 20 patients with chronic HCV Administration of silibinin: 1400 mg daily, infusion on 2 consecutive days Complete viral suppression in 13 of 20 patients; remaining HCV RNA negative during the subsequent follow up period Clinical trial Adeyemo et al [16] 32 patients with chronic HCV Administration of silymarin: 420 mg 3 times daily and 700 mg 3 times daily for 20 weeks No alteration in serum ALT and HCV RNA titers; suppression of C. albicans-induced T-cell IFNγ and phytohemagglutinin-induced T-cell proliferation; modest non-specific immunomodulatory effects in vivo by silymarin administration COVID-19 related article Molecular docking analysis Latha et al [17] Phytochemicals from the medicinal plants Docking analysis Better binding affinity to the target proteins of SARS-COV-2 than the synthetic repurposed drugs for treatment of COVID-19 Molecular docking analysis Saraswat, Singh, Patel [18] Phytochemicals from the medicinal plants ...…”

“…Flavonoid and polyphenol compounds such as luteolin, quercetin, genistein, and silymarin are known as natural ligands of peroxisome proliferator-activated receptor-γ, which decreases cytokine levels and suppresses the inflammatory pathways. Consequently, they might play a protective role against COVID-19-associated complications [18] . In this regard, polyphenol and flavonoid compounds' anti-inflammatory and antioxidant activity have been confirmed strongly [19] , [20] .…”

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline

“…However this is an emerging area and much more research is required to better understand the health promoting properties of flavonoids and polyphenolic substances delivered by the gut-lung and gut-brain axes, this may represent a new therapeutic frontier [451][452][453][454][455][456]. A number of recent studies have shown the potential of dietary flavonoids to treat neurodegenerative conditions [457,458], depression, anxiety and cognitive dysfunction [459][460][461][462] and Alzheimer's disease [463][464][465][466][467][468].…”

Characterization of flavonoids with potent and subtype-selective actions on estrogen receptors alpha and beta

“…In humans, flavonoids can affect multiple physiological pathways including angiogenesis, 13 bone regeneration, 13 , 14 , 15 and the inflammatory pathway. 16 , 17 Flavonoids have also been investigated as therapeutic agents for diseases such as atherosclerosis, 18 Alzheimer’s disease, 19 , 20 depression, 21 , 22 and several types of cancer, 23 , 24 , 25 , 26 , 27 as they have potential anti-oxidant and anti-inflammatory properties.…”