Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein

So, Masatomo; Kimura, Yasuyoshi; Yamaguchi, Keiichi; Sugiki, Toshihiko; Fujiwara, Toshimichi; Aguirre, César; Ikenaka, Kazuhiro; Mochizuki, Hideki; Kawata, Yasushi; Goto, Yuji

doi:10.1002/pro.4130

Cited by 15 publications

(9 citation statements)

References 71 publications

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“…It should be noted that the solubility of polyphenols, in particular, KMP could alter their effects on the formation of amyloid fibrils. For instance, So et al (2021) evaluated the effects of KMP‐7─O─glycoside on the amyloid formation of α‐synuclein (αSN). They reported that the formation of amyloid is substantially increased following interactions of insoluble KMP‐7─O─glycoside with αSN (So et al, 2021).…”

Section: Kmp Modulates Aβ‐induced Toxicity In Admentioning

confidence: 99%

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Kaempferol as a potential neuroprotector in Alzheimer's disease

Nejabati

Roshangar

2022

Journal of Food Biochemistry

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Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, is largely associated with cognitive disability, amnesia, and abnormal behavior, which accounts for about two third of people with dementia worldwide. A growing body of research demonstrates that AD is connected to several factors, such as aberrant accumulation of amyloid‐beta (Aβ), increase in the hyperphosphorylation of Tau protein, and the formation of neurofibrillary tangles, mitochondrial dysfunction, and inordinate production of reactive oxygen species (ROS). Despite remarkable efforts to realize the etiology and pathophysiology of AD, until now, scientists have not developed and introduced medications that can permanently cease the progression of AD. Thus, nowadays, research on the role of natural products in the treatment and prevention of AD has attracted great attention. Kaempferol (KMP), one of the prominent members of flavonols, exerts its ameliorative actions via attenuating oxidative stress and inflammation, reducing Aβ‐induced neurotoxicity, and regulating the cholinergic system. Therefore, in this review article, we outlined the possible effects of KMP in the prevention and treatment of AD. Practical applications Kaempferol (KMP) exerts its ameliorative actions against AD via attenuating oxidative stress and inflammation, reducing Aβ‐induced neurotoxicity, and regulating the cholinergic system. The beneficial effects of KMP were addressed in both in vitro and in vivo studies; however, conducting further research can warrant its long‐term effects as a safe agent. Therefore, after confirming its favorable functions in the prevention and treatment of AD, it could be used as a safe and effective agent.

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Section: Kmp Modulates Aβ‐induced Toxicity In Admentioning

confidence: 99%

“…For instance, So et al (2021) evaluated the effects of KMP‐7─O─glycoside on the amyloid formation of α‐synuclein (αSN). They reported that the formation of amyloid is substantially increased following interactions of insoluble KMP‐7─O─glycoside with αSN (So et al, 2021).…”

Section: Kmp Modulates Aβ‐induced Toxicity In Admentioning

confidence: 99%

Kaempferol as a potential neuroprotector in Alzheimer's disease

Nejabati

Roshangar

2022

Journal of Food Biochemistry

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“…In this study, RLS was used to test the antiaggregation effect of CTZ against the fibrillation of HEWL by measuring fluorescence at 350 nm [ 27 ]. HEWL was incubated at pH 2.0, 55 °C, and 600 rpm for 10 h to induce amyloid fibrillation.…”

Section: Resultsmentioning

confidence: 99%

“…A cosolute-dependent change in the solubility model has been reported in recent years. In this model, hydrophobic compounds protect proteins from interactions with aqueous solutions and promote protein prescription, which may lead to increased aggregation [ 27 , 55 ]. Soluble aggregates are expected to be the main components of this prescription because of the lack of change in Thioflavin-T fluorescence.…”

Section: Discussionmentioning

confidence: 99%

Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study

Altwaijry

Almutairi

Khan

et al. 2023

IJMS

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Amyloid fibrils abnormally accumulate together in the human body under certain conditions, which can result in lethal conditions. Thus, blocking this aggregation may prevent or treat this disease. Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension. Several previous studies suggest that diuretics prevent amyloid-related diseases and reduce amyloid aggregation. Thus, in this study we examine the effects of CTZ on hen egg white lysozyme (HEWL) aggregation using spectroscopic, docking, and microscopic approaches. Our results showed that under protein misfolding conditions of 55 °C, pH 2.0, and 600 rpm agitation, HEWL aggregated as evidenced by the increased turbidity and Rayleigh light scattering (RLS). Furthermore, thioflavin-T, as well as trans electron microscope (TEM) analysis confirmed the formation of amyloid structures. An anti-aggregation effect of CTZ is observed on HEWL aggregations. Circular dichroism (CD), TEM, and Thioflavin-T fluorescence show that both CTZ concentrations reduce the formation of amyloid fibrils as compared to fibrillated. The turbidity, RLS, and ANS fluorescence increase with CTZ increasing. This increase is attributed to the formation of a soluble aggregation. As evidenced by CD analysis, there was no significant difference in α-helix content and β-sheet content between at 10 µM CTZ and 100 µM. A TEM analysis of HEWL coincubated with CTZ at different concentrations validated all the above-mentioned results. The TEM results show that CTZ induces morphological changes in the typical structure of amyloid fibrils. The steady-state quenching study demonstrated that CTZ and HEWL bind spontaneously via hydrophobic interactions. HEWL–CTZ also interacts dynamically with changes in the environment surrounding tryptophan. Computational results revealed the binding of CTZ to ILE98, GLN57, ASP52, TRP108, TRP63, TRP63, ILE58, and ALA107 residues in HEWL via hydrophobic interactions and hydrogen bonds with a binding energy of −6.58 kcal mol−1. We suggest that at 10 µM and 100 μM, CTZ binds to the aggregation-prone region (APR) of HEWL and stabilizes it, thus preventing aggregation. Based on these findings, we can conclude that CTZ has antiamyloidogenic activity and can prevent fibril aggregation.

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“…Moreover, the concentration of free drugs in the plasma decreased quickly while drugs in the nanosystem stayed significantly longer in the plasma [ 96 ]. Kaempferol, a polyphenolic compound with antitumor activity, also faces the challenge of poor solubility [ 97 , 98 ]. A recent study reported a nanosystem incorporated with kaempferol that had excellent antitumor efficacy via disrupting calcium homeostasis in cancer cells [ 99 ].…”

Section: Advantages Of Nano-based Delivery Systems For Polyphenolic C...mentioning

confidence: 99%

Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges

Jia

Zhou

et al. 2023

Pharmaceuticals

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Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

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Polyphenol‐solubility alters amyloid fibril formation of α‐synuclein

Cited by 15 publications

References 71 publications

Kaempferol as a potential neuroprotector in Alzheimer's disease

Kaempferol as a potential neuroprotector in Alzheimer's disease

Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study

Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges

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