Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

Yamada, Masahito; Ono, Kenjiro; Hamaguchi, Tetsuya; Noguchi‐Shinohara, Moeko

doi:10.1007/978-3-319-18365-7_4

Cited by 57 publications

(54 citation statements)

References 121 publications

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“…Elevated intake of dietary polyphenols might be relevant to the prevention of amyloidosis. Nutraceutical strategies might become a way to reduce the risk of certain amyloid diseases [19,21]. Many drugs used today are natural products or derivatives of natural products [22][23].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines

Kotormán

Kasi

Halász

et al. 2017

PPL

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Abstract:The aim of the present study was to examine the potential role and applicability of dietary supplements in reducing the risk of development of amyloid diseases associated with the gastrointestinal tract, such as type II diabetes. Trypsin, a well-known serine protease was used as a model protein in our experiments. The effect of various red wines on the formation of amyloid-like fibrils of trypsin was studied in vitro, in aqueous ethanol, at pH 7.0. Turbidity measurements, aggregation kinetics experiments, Congo red binding assays and electronic circular dichroism spectroscopic measurements were used to follow the aggregation process in the presence or absence of various red wines. The results suggest that red wines effectively inhibit the formation of amyloid-like fibrils of trypsin and the inhibitory effect is dose-dependent. The extent of inhibition was found to be proportional to the total concentration of phenolic compounds.

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Section: Introductionmentioning

confidence: 99%

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines

Kotormán

Kasi

Halász

et al. 2017

PPL

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“…Several biological activities are attributed to RA, such as antioxidant and anti-inflammatory properties and neuroprotective effects [26][27][28][29][30] . RA has been proven to be effective in experimental models of neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis [31,32] , and recently it was shown to have the interesting effect of reducing seizures in rats [27,[33][34][35] . A previous study showed that RA inhibits the activity of GABA-T.…”

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confidence: 99%

Rosmarinic Acid Attenuates the Activation of Murine Microglial N9 Cells through the Downregulation of Inflammatory Cytokines and Cleaved Caspase-3

Coelho

Viau²,

Staub³

et al. 2017

Neuroimmunomodulation

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Objective: The present study evaluated the ability of rosmarinic acid (RA) to inhibit microglia activation induced by lipopolysaccharide (LPS) in the N9 murine microglial cell line, and investigated the putative mechanisms involved in this process. Methods: In all tests, N9 murine microglial cells were pretreated with RA (0.1, 1.0, and 10 μM) for 20 h and exposed to LPS (1 μM/mL) for 4 h. Cell viability was measured by Trypan blue exclusion assay. Flow cytometry was used to detect reactive oxygen species (ROS), quantify cleaved caspase-3, and analyze the mitochondrial electrochemical potential. iNOS, Arg-1, TNF-α, IL-1β, and IL-6 proteins were analyzed by Western blotting, and their antigens were detected using the chemiluminescence technique. The effect of RA on DNA was evaluated by the Comet assay. Results: RA attenuated the expression of the M1 marker iNOS and the levels of proinflammatory factors, including TNF-α, IL-1β, and IL-6; it increased the expression of the M2 marker Arg-1, and inhibited, at least in part, ROS generation and loss of mitochondrial outer membrane permeabilization through the inhibition of cleaved caspase-3 activation. RA also inhibited DNA damage, reassuring cell protection. Conclusions: The results suggested a protective effect of RA through downregulation of inflammatory cytokines and cleaved caspase-3.

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“…38 Similar anti-amyloidogenic effects were also reported in studies with mice for 1 , 3 , and 11 , supporting the potential preventive properties of these natural compounds against AD. 39 …”

Section: Resultsmentioning

confidence: 99%

Potential Antiosteoporotic Natural Product Lead Compounds That Inhibit 17β-Hydroxysteroid Dehydrogenase Type 2

et al. 2017

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17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) converts the active steroid hormones estradiol, testosterone, and 5α-dihydrotestosterone into their weakly active forms estrone, Δ4-androstene-3,17-dione, and 5α-androstane-3,17-dione, respectively, thereby regulating cell- and tissue-specific steroid action. As reduced levels of active steroids are associated with compromised bone health and onset of osteoporosis, 17β-HSD2 is considered a target for antiosteoporotic treatment. In this study, a pharmacophore model based on 17β-HSD2 inhibitors was applied to a virtual screening of various databases containing natural products in order to discover new lead structures from nature. In total, 36 hit molecules were selected for biological evaluation. Of these compounds, 12 inhibited 17β-HSD2 with nanomolar to low micromolar IC50 values. The most potent compounds, nordihydroguaiaretic acid (1), IC50 0.38 ± 0.04 μM, (−)-dihydroguaiaretic acid (4), IC50 0.94 ± 0.02 μM, isoliquiritigenin (6), IC50 0.36 ± 0.08 μM, and ethyl vanillate (12), IC50 1.28 ± 0.26 μM, showed 8-fold or higher selectivity over 17β-HSD1. As some of the identified compounds belong to the same structural class, structure–activity relationships were derived for these molecules. Thus, this study describes new 17β-HSD2 inhibitors from nature and provides insights into the binding pocket of 17β-HSD2, offering a promising starting point for further research in this area.

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Natural Phenolic Compounds as Therapeutic and Preventive Agents for Cerebral Amyloidosis

Cited by 57 publications

References 121 publications

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines

Inhibition of Amyloid-like Fibril Formation of Trypsin by Red Wines

Rosmarinic Acid Attenuates the Activation of Murine Microglial N9 Cells through the Downregulation of Inflammatory Cytokines and Cleaved Caspase-3

Potential Antiosteoporotic Natural Product Lead Compounds That Inhibit 17β-Hydroxysteroid Dehydrogenase Type 2

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