<i>Washingtonia filifera</i> seed extracts inhibit the islet amyloid polypeptide fibrils formations and α-amylase and α-glucosidase activity

Floris, Sonia; Fais, Antonella; Medda, Rosaria; Pintus, Francesca; Piras, Alessandra; Kumar, Amit; Kuś, Piotr Marek; Westermark, Gunilla T.; Era, Benedetta

doi:10.1080/14756366.2021.1874945

Cited by 15 publications

(6 citation statements)

References 41 publications

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“…To inhibit hIAPP oligomerization is a promising strategy to prevent the pathological process of hIAPP. Inhibitors such as small molecules [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ], nanoparticles [ 31 , 32 , 33 ], short peptides [ 34 , 35 , 36 ], etc. have been developed to act on hIAPP misfolding and oligomerization.…”

Section: Introductionmentioning

confidence: 99%

Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation

Wang

Zhu

Song

et al. 2022

IJMS

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The pathogenesis of type 2 diabetes (T2D) is highly related to the abnormal self-assembly of the human islet amyloid polypeptide (hIAPP) into amyloid aggregates. To inhibit hIAPP aggregation is considered a promising therapeutic strategy for T2D treatment. Melatonin (Mel) was reported to effectively impede the accumulation of hIAPP aggregates and dissolve preformed fibrils. However, the underlying mechanism at the atomic level remains elusive. Here, we performed replica-exchange molecular dynamics (REMD) simulations to investigate the inhibitory effect of Mel on hIAPP oligomerization by using hIAPP20–29 octamer as templates. The conformational ensemble shows that Mel molecules can significantly prevent the β-sheet and backbone hydrogen bond formation of hIAPP20–29 octamer and remodel hIAPP oligomers and transform them into less compact conformations with more disordered contents. The interaction analysis shows that the binding behavior of Mel is dominated by hydrogen bonding with a peptide backbone and strengthened by aromatic stacking and CH–π interactions with peptide sidechains. The strong hIAPP–Mel interaction disrupts the hIAPP20–29 association, which is supposed to inhibit amyloid aggregation and cytotoxicity. We also performed conventional MD simulations to investigate the influence and binding affinity of Mel on the preformed hIAPP1–37 fibrillar octamer. Mel was found to preferentially bind to the amyloidogenic region hIAPP20–29, whereas it has a slight influence on the structural stability of the preformed fibrils. Our findings illustrate a possible pathway by which Mel alleviates diabetes symptoms from the perspective of Mel inhibiting amyloid deposits. This work reveals the inhibitory mechanism of Mel against hIAPP20–29 oligomerization, which provides useful clues for the development of efficient anti-amyloid agents.

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Section: Introductionmentioning

confidence: 99%

Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation

Wang

Zhu

Song

et al. 2022

IJMS

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“…Natural products are more complex than synthetic compounds, and drugs based on natural product structures exhibit better chemical diversity and occupy larger regions of chemical space than drugs of completely synthetic origins [ 16 , 55 ]. Components or compounds obtained through LC-MS analysis from Helichrysum petiolare extract, including protocatechuic acid, arbutin, engeletin, 3-caffeoylquinic acid, are reported to elicit anti-diabetic properties through the inhibition of α-amylase and α-glucosidase enzymes [ 56 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

et al. 2021

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Diabetes mellitus (DM) is a chronic metabolic condition that can lead to significant complications and a high fatality rate worldwide. Efforts are ramping up to find and develop novel α-glucosidase and α-amylase inhibitors that are both effective and potentially safe. Traditional methodologies are being replaced with new techniques that are less complicated and less time demanding; yet, both the experimental and computational strategies are viable and complementary in drug discovery and development. As a result, this study was conducted to investigate the in vitro anti-diabetic potential of aqueous acetone Helichrysum petiolare and B.L Burtt extract (AAHPE) using a 2-NBDG, 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxy-d-glucose uptake assay. In addition, we performed molecular docking of the flavonoid constituents identified and quantified by liquid chromatography-mass spectrometry (LC-MS) from AAHPE with the potential to serve as effective and safe α-amylase and α-glucosidase inhibitors, which are important in drug discovery and development. The results showed that AAHPE is a potential inhibitor of both α-amylase and α-glucosidase, with IC50 values of 46.50 ± 6.17 (µg/mL) and 37.81 ± 5.15 (µg/mL), respectively. This is demonstrated by a significant increase in the glucose uptake activity percentage in a concentration-dependent manner compared to the control, with the highest AAHPE concentration of 75 µg/mL of glucose uptake activity being higher than metformin, a standard anti-diabetic drug, in the insulin-resistant HepG2 cell line. The molecular docking results displayed that the constituents strongly bind α-amylase and α-glucosidase while achieving better binding affinities that ranged from ΔG = −7.2 to −9.6 kcal/mol (compared with acarbose ΔG = −6.1 kcal/mol) for α-amylase, and ΔG = −7.3 to −9.0 kcal/mol (compared with acarbose ΔG = −6.3 kcal/mol) for α-glucosidase. This study revealed the potential use of the H. petiolare plant extract and its phytochemicals, which could be explored to develop potent and safe α-amylase and α-glucosidase inhibitors to treat postprandial glycemic levels in diabetic patients.

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“…The α-glucosidase and α-amylase inhibitory activities of different samples (CSFP, CSFP1-β, and CSFP2-α) were assessed according to the previously reported methods ( 26 , 27 ). Acarbose (Ac) was used as a positive control.…”

Section: Methodsmentioning

confidence: 99%

Two Novel Polysaccharides From Clitocybe squamulosa: Their Isolation, Structures, and Bioactivities

Guo

Lei

et al. 2022

Front. Nutr.

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The crude polysaccharides from the fruiting bodies of Clitocybe squamulosa (CSFP) were isolated by hot-water extraction. Two novel polysaccharides, CSFP1-β and CSFP2-α, were further purified by DEAE-52 anion exchange and Sephacryl S-400 gel filtration chromatography, and the purities reached 98.44 and 97.83%, respectively. The structural characteristics and bioactivities of CSFP, CSFP1-β, and CSFP2-α were identified by the combination of chemical and instrumental analysis. Results showed that CSFP was formed by the aggregation of honeycomb spherical materials; CSFP1-β and CSFP2-α were interwoven by reticular and fibrous structures, respectively. Purified components of both CSFP1-β and CSFP2-α showed typical infrared absorption peaks of polysaccharides, and contents of nucleic acid and protein decreased significantly. Simultaneously, CSFP with a molecular weight (Mw) of 1.948 × 104 Da were composed mainly of glucose, mannose, galactose, and rhamnose. CSFP1-β was composed mainly of glucose, galactose, and mannose, while CSFP2-α was composed of glucose, and both their Mw distributions were uneven. Compared with CSFP, the antioxidant activities of CSFP1-β and CSFP2-α were significantly improved (p < 0.05), and they both showed good abilities to bind free cholesterol and bile acid salts in vitro. The binding abilities of the two compounds were found to be 68.62 and 64.43%, and 46.66 and 45.05 mg/g, respectively. CSFP, CSFP1-β, and CSFP2-α had good bacteriostatic effects with a linear increasing relationship to increasing concentration. In addition, CSFP promoted the growth of RAW264.7 cells and has potential immunomodulatory, anti-inflammatory, and anti-tumor activities.

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Washingtonia filifera seed extracts inhibit the islet amyloid polypeptide fibrils formations and α-amylase and α-glucosidase activity

Cited by 15 publications

References 41 publications

Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation

Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation

In Vitro Evaluation of the Anti-Diabetic Potential of Aqueous Acetone Helichrysum petiolare Extract (AAHPE) with Molecular Docking Relevance in Diabetes Mellitus

Two Novel Polysaccharides From Clitocybe squamulosa: Their Isolation, Structures, and Bioactivities

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