The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Ueda, Tomoyuki; Inden, Masatoshi; Shirai, Katsuhiro; Sekine, Shin-ichiro; Masaki, Yuji; Kurita, Hisaka; Ichihara, Kenji; Ishii, Takashi; Hozumi, Isao

doi:10.1038/s41598-017-03115-y

Cited by 57 publications

(66 citation statements)

References 37 publications

(62 reference statements)

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“…Hence, the geometrical properties of protein upon binding the ligands suggested that kaempferol could be a better promising therapeutic drug candidate than kaempferide, which could hinder the formation of aggregates in mutant SOD1. Moreover, our results corroborated with the reports from the experimental studies asserting that kaempferol has greater ability in impeding the formation of aggregates in mutant SOD1 [25].…”

Section: Impact Of Kaempferol and Kaempferide On The Secondary Structsupporting

confidence: 91%

“…Numerous biological and pharmacological properties, such as antibacterial, anti-inflammatory, and antioxidative activity are reported with propolis [27,28]. Two polyphenols derived from propolis, kaempferol, and kaempferide are its major effective components, which are known to have neuroprotective properties against mutant SOD1 protein as reported from the recent experimental studies [25].…”

Section: Introductionmentioning

confidence: 98%

“…Hence, we utilized DMD approach to decipher the formation of aggregates in mutant SOD1. Recent experimental reports suggested that kaempferol and kaempferide could act as an effective therapeutic against the aggregated SOD1 protein [25].…”

Section: Introductionmentioning

confidence: 99%

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Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: A quantum chemical and molecular mechanics study

Srinivasan

Rajasekaran

2018

BioFactors

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Mutation in Cu/Zn superoxide dismutase (SOD1) at position 85 from glycine to arginine was found to be a prominent cause of aggregation characterized by an increased content of β-sheets in familial amyotrophic lateral sclerosis (fALS). Various literatures reported that natural polyphenols could act as a β-sheet breaker and therefore, treated as a potential therapeutics against various aggregated proteins involved in neurodegenerative disorders. Through computational perspective, molecular docking, quantum chemical studies, and discrete molecular dynamics were implemented to study the binding and structural effect of natural polyphenols, kaempferol, and kaempferide on mutant SOD1. Kaempferol exhibited significant binding and greater residual energy contribution with mutant SOD1 than kaempferide. More interestingly, kaempferol was found to reduce the β-sheet content augmenting the mutant conformational stability and flexibility relative to that of kaempferide. Hence, the inhibition of mutant SOD1 aggregation by kaempferol was explored, thereby suggesting kaempferol could act as a drug candidate for the design of the natural therapeutics against fALS. © 2018 BioFactors, 44(5): [431][432][433][434][435][436][437][438][439][440][441][442] 2018

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Section: Impact Of Kaempferol and Kaempferide On The Secondary Structsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 98%

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Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: A quantum chemical and molecular mechanics study

Srinivasan

Rajasekaran

2018

BioFactors

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“…Although the detailed chemical composition of various types of propolis differ, based on geographical origin, in general, typical raw propolis contains 50% resins and vegetable balsams, 30% waxes, 10% essential and aromatic oil, 5% pollen, and 5% other bioactive compounds (Popova, Reyes, Le Conte, & Bankova, ). This product has been extensively used in foods, beverages, and nutritional supplements, because of bioactive constituents such as phenolic compounds, flavonoids, terpenes, beta‐steroids, and aromatic acids (Popova et al, ; T. Ueda et al, ). The health‐promoting properties of propolis have been investigated in various animal studies (Seven, Yilmaz, Seven, & Kelestemur, ; Yildirim et al, ).…”

Section: Introductionmentioning

confidence: 99%

The efficacy of propolis on markers of glycemic control in adults with type 2 diabetes mellitus: A systematic review and meta‐analysis

Karimian

Hadi

Pourmasoumi

et al. 2019

Phytotherapy Research

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Background and Objectives The impetus for the current study was to evaluate the efficacy of propolis supplementation on markers of glycemic status in adults with type 2 diabetes mellitus (T2DM). Methods A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, Web of Science, and Google Scholar up to August 2018, identifying randomized controlled trials investigating the effect of propolis supplementation on glycemic markers in adults with T2DM. Cochrane Collaboration tool was used to evaluate the risk of bias assessment. A random‐effects model was applied in the meta‐analysis to compensate for potential heterogeneity among the included studies. Results Six randomized controlled trials comprising 373 participants were included in the systematic review and meta‐analysis. The results of the meta‐analysis revealed significant reductions in fasting plasma glucose (−13.51 mg/dl; 95% CI [−24.98, −2.04]) and hemoglobin A1C (−0.52%; 95% CI [−0.94, −0.10]) concentrations following propolis supplementation. However, no significant lowering effect was observed in fasting insulin levels (−0.53 pmol/L; 95% CI [−1.69, 0.63]) or homeostasis model assessment of insulin resistance (−0.543; 95% CI [−1.72, 0.64]). Conclusion This systematic review and meta‐analysis suggested that propolis supplementation may be effective in controlling glycemic levels for T2DM patients. Further studies are needed to confirm these results.

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“…Currently, more than 180 types of SOD1 pathogenic mutations have been identi ed in ALS patients [33]. Among those, the pathogenic SOD1 G85R mutation has been most frequently studied [34,35,36,37].…”

Section: Introductionmentioning

confidence: 99%

The neuroprotective effects of α7 nicotinic acetylcholine receptor against mutant copper-zinc superoxide dismutase 1-mediated toxicity

Hozumi

Ito

Inden

et al. 2020

Preprint

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BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. Although many drugs have entered clinical trials, few have shown effectiveness in the treatment of ALS. Previous studies searching for causal genes associated with familial ALS identified the copper-zinc superoxide dismutase 1 (SOD1). Other studies have shown that the stimulation of α7 nicotinic acetylcholine receptor (nAChR) can have neuroprotective effects in some models of neurodegenerative disease, as well as prevent glutamate-induced motor neuronal death. However, the effect of α7 nAChR agonists on mutant SOD1 aggregates in motor neurons remains unclear.MethodsWe examined whether α7 nAChR activation had a neuroprotective effect against SOD1G85R-induced toxicity in a cellular model for ALS. Furthermore, the mechanism was also examined by Western blot analysis and qRT-PCR.ResultsWe found that α7 nAChR activation showed significant neuroprotective effects against SOD1G85R-induced toxicity via the reduction of intracellular protein aggregates. This reduction also correlated with the activation of autophagy through the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the activation of α7 nAChRs was found to increase the biogenesis of lysosomes by inducing translocation of the transcription factor EB (TFEB) into the nucleus.ConclusionsThese results support the therapeutic potential of α7 nAChR activation in diseases that are characterized by SOD1G85R aggregates, such as ALS.

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The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutase-mediated toxicity

Cited by 57 publications

References 37 publications

Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: A quantum chemical and molecular mechanics study

Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: A quantum chemical and molecular mechanics study

The efficacy of propolis on markers of glycemic control in adults with type 2 diabetes mellitus: A systematic review and meta‐analysis

The neuroprotective effects of α7 nicotinic acetylcholine receptor against mutant copper-zinc superoxide dismutase 1-mediated toxicity

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