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A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination
https://onlinelibrary.wiley.com/doi/abs ... glia.23715

Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA‐mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin‐induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.

From 2003...

Flavonoids inhibit myelin phagocytosis by macrophages; a structure–activity
relationship study
Biochemical Pharmacology. 2003 Mar 1;65(5):877-85.

Demyelination is a characteristic hallmark of the neuro-inflammatory disease multiple sclerosis. During demyelination, macrophages phagocytose myelin and secrete inflammatory mediators that worsen the disease. Here, we investigated whether flavonoids, naturally occurring immunomodulating compounds, are able to influence myelin phagocytosis by macrophages in vitro. The flavonoids luteolin, quercetin and fisetin most significantly decreased the amount of myelin phagocytosed by a macrophage cell line without affecting its viability. ic50 values for these compounds ranged from 20 to 80 μM. The flavonoid structure appeared to be essential for observed effects as flavonoids containing hydroxyl groups at the B-3 and B-4 positions in combination with a C-2,3 double bond were most effective. The capacity of the various flavonoids to inhibit phagocytosis correlated well with their potency as antioxidant, which is in line with the requirement of reactive oxygen species for the phagocytosis of myelin by macrophages. Our results implicate that flavonoids may be able to limit the demyelination process during multiple sclerosis.

2020 Oct 24
Department of Neurology, School of Medicine, University of Missouri, Columbia, Missouri
Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma
https://pubmed.ncbi.nlm.nih.gov/33098588/

Abstract

Neuroinflammation leads to neurodegeneration, cognitive defects, and neurodegenerative disorders. Neurotrauma/traumatic brain injury (TBI) can cause activation of glial cells, neurons, and neuroimmune cells in the brain to release neuroinflammatory mediators. Neurotrauma leads to immediate primary brain damage (direct damage), neuroinflammatory responses, neuroinflammation, and late secondary brain damage (indirect) through neuroinflammatory mechanism. Secondary brain damage leads to chronic inflammation and the onset and progression of neurodegenerative diseases. Currently, there are no effective and specific therapeutic options to treat these brain damages or neurodegenerative diseases. Flavone luteolin is an important natural polyphenol present in several plants that show anti-inflammatory, antioxidant, anticancer, cytoprotective, and macrophage polarization effects. In this short review article, we have reviewed the neuroprotective effects of luteolin in neurotrauma and neurodegenerative disorders and pathways involved in this mechanism. We have collected data for this study from publications in the PubMed using the keywords luteolin and mast cells, neuroinflammation, neurodegenerative diseases, and TBI. Recent reports suggest that luteolin suppresses systemic and neuroinflammatory responses in Coronavirus disease 2019 (COVID-19). Studies have shown that luteolin exhibits neuroprotective effects through various mechanisms, including suppressing immune cell activation, such as mast cells, and inflammatory mediators released from these cells. In addition, luteolin can suppress neuroinflammatory response, activation of microglia and astrocytes, oxidative stress, neuroinflammation, and the severity of neuroinflammatory diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and TBI pathogenesis. In conclusion, luteolin can improve cognitive decline and enhance neuroprotection in neurodegenerative diseases, TBI, and stroke.

The following page lists luteolin content in various foods. It seems that radicchio has the highest content by an 8x factor over the next highest food, green bell peppers. The values are 38 mg/100 g for radicchio and 4.7 mg/100 g for green bell peppers.

37 Luteolin Rich Foods Ranked by Luteolin Density
https://myintakepro.com/blog/luteolin-rich-foods/

Note: Use this link to view an interactive chart. You can even download the data into your spreadsheet.

NHE wrote: ↑Thu Nov 05, 2020 4:30 amThe following page lists luteolin content in various foods. It seems that radicchio has the highest content by an 8x factor over the next highest food, green bell peppers. The values are 38 mg/100 g for radicchio and 4.7 mg/100 g for green bell peppers.

Radicchio is also fairly high in quercetin as are red onions. Radicchio is 31.5 mg quercetin per 100 g. Red onions are at 39.2 mg quercetin per 100 g (but are quite low in luteolin at 0.16 mg/100 g). The USDA has tabulated a variety of foods for flavonoid content. https://www.ars.usda.gov/ARSUserFiles/8 ... lav3.2.pdf

NHE wrote: ↑Thu Nov 05, 2020 4:30 am The following page lists luteolin content in various foods. It seems that radicchio has the highest content by an 8x factor over the next highest food, green bell peppers. The values are 38 mg/100 g for radicchio and 4.7 mg/100 g for green bell peppers.

37 Luteolin Rich Foods Ranked by Luteolin Density
https://myintakepro.com/blog/luteolin-rich-foods/

I've recently added radicchio to my diet. Has anyone else tried this? I found that the flavor of raw radicchio is a bit strong, so I add it to my veggie sautes.

Luteolin can also be found in peppermint tea.

Commercial peppermint (Mentha × piperita L.) teas: Antichlamydial effect and polyphenolic composition
Food Research International, 2013 (53) 758-766.

The qualitative and quantitative polyphenolic contents in the infusions of the commercial peppermint tea (Mentha × piperita L.) samples (n = 27) from different countries were studied using HPLC–UV-MS/MS analysis. The most abundant polyphenolics in the peppermint infusion were eriocitrin, 12-hydroxyjasmonate sulfate, luteolin-O-rutinoside and rosmarinic acid. In order to evaluate the content of samples by finding chemosystematic markers, the essential oil composition was studied by GC. The analyses showed that the 24 (89%) peppermint tea samples contained peppermint, whereas three samples may contain Mentha spicata, different from that claimed on the package. The effects of seven peppermint tea extracts against respiratory tract pathogen Chlamydia pneumoniae were investigated in vitro. All seven selected tea extracts were active against C. pneumoniae, the growth inhibition ranging from 20.7% to 69.5% at extract concentration of 250 μg/ml. In most cases, the antichlamydial activity was related to the peppermint teas having also high content of luteolin and apigenin glycosides. This study supports the consumption of peppermint tea to potentially elicit beneficial health effects on acute respiratory tract infections.

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