Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells

Sasaki, Hiroaki; Kitoh, Yuki; Tsukada, Mariko; Miki, Kazuhiko; Koyama, Kiyotaka; Juliawaty, Lia Dewi; Hakim, Euis H.; Takahashi, Kunio; Kinoshita, Kaoru

doi:10.1016/j.bmcl.2015.04.106

Cited by 27 publications

(15 citation statements)

References 31 publications

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“…They are polyphenolic compounds synthesized in response to stress and found in fruits, seeds, grains, vegetables, flowers, wines and teas [32]. Biflavonoids are a specific class of flavonoids composed of a combination of C-C or C-O-C bonded flavonoid dimers [33] and have shown greater pharmaceutical efficiency than their respective monomers [34]. Here, using an established LPS and IL-1β model of neuroinflammation [35], we demonstrated that the biflavonoid agathisflavone (FAB) had potent neuroprotective and immunomodulatory effects in neuron-glial cocultures.…”

Section: Discussionmentioning

confidence: 99%

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

et al. 2020

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Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

et al. 2020

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“…Ginkgolic acid has also demonstrated antimicrobial properties, specifically against E. coli and Staphlylococcus aureus [ 125 ]. Isoginkgetin has been shown to provide neuroprotection against the cytotoxic effects of excessive Aβ accumulation [ 128 , 129 ], while also having anti-microbial and anti-fungal activity [ 126 ]. Our lab’s preliminary work in testing these three compounds in AD determined their effectiveness in reducing Aβ load in vitro, further supporting their therapeutic potential in AD.…”

Section: Potential Novel Therapeuticsmentioning

confidence: 99%

The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

Iqbal

Zeng

Pasinetti

2020

IJMS

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The aggregation and accumulation of amyloid-β plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer’s disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-β peptides being limited at best, a greater understanding of the physiological role of amyloid-β peptides is needed. The development of amyloid-β plaques has been determined to occur 10–20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-β peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-β plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-β, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer’s disease.

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“…The anti-inflammatory activity has been related to the inhibition of arachidonic acid [84], the inhibition of COX-2 [85], SOD [86], cAMP phosphodiesterases [87], and the suppression of lymphocyte proliferation [88]. Other activities include the neuroprotector and cytoprotector effects when cells are exposed either to external or intrinsic factors like UV radiation [89] or the accumulation of β -amyloid in neurons [90, 91]. This extract has also been shown to increase adiponectin secretion [92] and the activity of AMP-kinases [93].…”

Section: Microbial Metabolites That Regulate Splicingmentioning

confidence: 99%

Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment

Martínez-Montiel

Rosas-Murrieta

Martínez-Montiel

et al. 2016

BioMed Research International

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In eukaryotes, genes are frequently interrupted with noncoding sequences named introns. Alternative splicing is a nuclear mechanism by which these introns are removed and flanking coding regions named exons are joined together to generate a message that will be translated in the cytoplasm. This mechanism is catalyzed by a complex machinery known as the spliceosome, which is conformed by more than 300 proteins and ribonucleoproteins that activate and regulate the precision of gene expression when assembled. It has been proposed that several genetic diseases are related to defects in the splicing process, including cancer. For this reason, natural products that show the ability to regulate splicing have attracted enormous attention due to its potential use for cancer treatment. Some microbial metabolites have shown the ability to inhibit gene splicing and the molecular mechanism responsible for this inhibition is being studied for future applications. Here, we summarize the main types of natural products that have been characterized as splicing inhibitors, the recent advances regarding molecular and cellular effects related to these molecules, and the applications reported so far in cancer therapeutics.

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Inhibitory activities of biflavonoids against amyloid-β peptide 42 cytotoxicity in PC-12 cells

Cited by 27 publications

References 31 publications

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

The Use of Antimicrobial and Antiviral Drugs in Alzheimer’s Disease

Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment

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