Revealing the Mechanism of EGCG, Genistein, Rutin, Quercetin, and Silibinin Against hIAPP Aggregation via Computational Simulations

AbstractTo inhibit hIAPP aggregation and reduce toxicity of its oligomers are one of the potential strategies for the treatment of Type 2 diabetes (T2D). It has been reported that there is an effective inhibitory effect on hIAPP aggregation by five natural flavonoids, including Genistein, Rutin, Quercetin, Epigallocatechin gallate (EGCG), and Silibinin, which are widely found in our daily food. However, the detailed mechanisms to inhibit hIAPP aggregation remain unclear. Here, we explore the mechanisms of the five flavonoids against hIAPP aggregation by molecular docking and molecular dynamics simulations. We show that these flavonoids can disaggregate Chain A and Chain B of hIAPP to reduce the extended conformation by binding with two regions of hIAPP, Leu12–Ala13–Asn14 and Asn31–Val32–Gly33–Ser34–Asn35, with the inhibitory ability of Genistein  >  Rutin >  Quercetin >  EGCG >  Silibinin. These five compounds exhibit a common mechanism for disaggregation of the hIAPP pentamer; that is, they loosen the two nearest peptide chains to potentially destroy the hIAPP oligomer. Mutations of eight key residues remarkably affected by the flavonoids indicate that the secondary str uctures of the hIAPP pentamer change from β-sheet to be random coil, thereby to destroy its structural stability; moreover, the 28th (Ser), 12th (Leu) and 32nd (Val) amino acids exhibit significant eff...
Source: Interdisciplinary Sciences, Computational Life Sciences - Category: Bioinformatics Source Type: research

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Publication date: Available online 15 February 2020Source: Life SciencesAuthor(s): Adham M. Maher, Samar R. Saleh, Nihal M. Elguindy, Hagar M. Hashem, Galila A. YacoutAbstractAim of the workNeuroinflammation can arise from metabolic disturbances accompanying type 2 diabetes mellitus (T2DM) with an implication of indoleamine 2,3-dioxygenase 1 (IDO1). The antioxidant and anti-inflammatory potentials of melatonin (Mel) can amend diabetic complications. Here, we examined the effect of exogenous melatonin on neuroinflammation in high fat diet (HFD)-induced T2DM rats.Main methodsTwenty-one adult male Sprague-dawley rats were div...
Source: Life Sciences - Category: Biology Source Type: research
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Source: Primary Care Diabetes - Category: Primary Care Authors: Tags: Original research Source Type: research
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Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
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Source: Canadian Journal of Gastroenterology - Category: Gastroenterology Tags: Can J Gastroenterol Hepatol Source Type: research
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Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
Authors: Maejima T, Kumagai K, Yabe K, Yasuno K, Ishikawa K, Okado K, Sasaki N, Kai K, Mori K Abstract A 40-week-old male spontaneous diabetic Torii rat, an animal model of type 2 diabetes mellitus, was found to have marked urinary calculi with hematuria in the urinary bladder on necropsy. Histological findings in the urinary bladder included a papillary growth pattern with a fibrovascular stroma without atypia. Fine granular materials in the bladder lumen were positive for Von Kossa staining but negative for periodic acid-Schiff or Gram staining, indicating no apparent bacterial infection in the urinary bladder. S...
Source: Journal of Toxicologic Pathology - Category: Toxicology Tags: J Toxicol Pathol Source Type: research
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Source: Annals of Surgical Treatment and Research - Category: Surgery Tags: Ann Surg Treat Res Source Type: research
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
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Source: Archives of Medical Science - Category: General Medicine Tags: Arch Med Sci Source Type: research
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