Investigation of the Effect of Pyrogallol on the Formation of Amylin Amyloid Fibrils as a Strategy for the Treatment of Type 2 Diabetic Patients: A Theoretical and Experimental Study.

In more than 50 to 90% of type 2 diabetic patients, under the influence of various factors, the production of islet amyloid polypeptide or amylin in pancreatic beta cells increases. Spontaneous accumulation of amylin peptide in the form of insoluble amyloid fibrils and soluble oligomers is one of the main causes of beta cell death in diabetic patients. The objective of the present study was to evaluate the effect of pyrogallol, as a phenolic compound, on inhibiting the formation of amylin protein amyloid fibrils. In this study, different techniques such as the thioflavin T (ThT) and 1-Anilino-8-naphthalene sulfonate (ANS) fluorescence intensity and the circular dichroism (CD) spectrum, will be used to investigate the effects of this compound on inhibiting the formation of amyloid fibrils. To investigate the interaction sites of pyrogallol with amylin, docking studies were performed. Our results that pyrogallol in a dose-dependent manner (0.5:1, 1:1, and 5:1, Pyr to Amylin) inhibits the amylin amyloid fibrils formation. Docking analysis revealed that pyrogallol forms hydrogen bonds with valine 17 and asparagine 21. In addition, this compound forms 2 more hydrogen bonds with asparagine 22. This compound also forms hydrophobic bonds with histidine 18. Considering this data and the direct relationship between oxidative stress and the formation of amylin amyloid accumulations in diabetes, the use of compounds with both antioxidant and anti-amyloid properties can be considered an important therapeutic strategy for type 2 diabetes.

Genotype- and tissue-specific physiological and biochemical changes of two chickpea (Cicer arietinum) varieties following a rapid dehydration.

In nature, plants may suffer rapid dehydration (RD), which causes significant loss of the annual global chickpea production. Thus, ascertaining more knowledge concerning the RD-tolerance mechanisms in chickpea is crucial for developing high drought-tolerant varieties to assure sustainable chickpea production under sudden water deficit. Here, we focused on genotype-driven variation in leaf relative water content (RWC) and associated differences in RD-responsive physiological and biochemical attributes in roots and leaves of two chickpea varieties, FLIP00-21C and FLIP02-89C, subjected to well-watered and RD conditions. FLIP00-21C showed higher RD-tolerance than FLIP02-89C, evident by its higher leaf RWC during RD. Consistently, FLIP00-21C exhibited lower membrane injury due to lower hydrogen peroxide (H2 O2 ) accumulation than FLIP02-89C during RD, indicating reduced RD-induced oxidative damage. Under RD conditions, total phenolics in roots and flavonoids in roots and leaves increased more in FLIP02-89C compared to FLIP00-21C; however, the increased activities of superoxide dismutase and H2 O2 -scavenging enzymes were more properly coordinated in FLIP00-21C than in FLIP02-89C, which might contribute to more efficient antioxidant defense in FLIP00-21C than in FLIP02-89C. The higher leaf RWC of FLIP00-21C versus FLIP02-89C under RD might be associated with greater increases in the levels of the osmo-regulators proline and total free amino acids (TFAAs) in FLIP00-21C than in FLIP02-89C. Collectively, the higher RD-tolerance of FLIP00-21C is mainly associated with the maintenance of higher RWC, stronger antioxidant defense, and greater accumulation of proline and TFAAs. These traits could be useful for evaluating the drought-tolerance of chickpea varieties and further marker-assisted breeding approaches for improvement of chickpea productivity.