Inhibitory Activities of Antioxidant Flavonoids from <i>Tamarix gallica</i> on Amyloid Aggregation Related to Alzheimer’s and Type 2 Diabetes Diseases

Abstract

The prevention of amyloid aggregation is promising for the treatment of age-related diseases such as Alzheimer's (AD) and type 2 diabetes (T2D). Ten antioxidant flavonoids isolated from the medicinal halophyte Tamarix gallica were tested for their amyloid aggregation inhibition potential. Glucuronosylated flavonoids show relatively strong inhibitory activity of Amyloid β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregation compared to their aglycone analogs. Structure-activity relationship of the flavonoids suggests that the catechol moiety is important for amyloid aggregation inhibition, while the methylation of the carboxyl group in the glucuronide moiety and of the hydroxyl group in the aglycone flavonoids decreased it.Key words amyloid aggregation; glucuronosylated flavonoid; Tamarix gallica; Alzheimer's disease; type 2 diabetes The incidence of both disturbances Alzheimer's disease (AD) and type 2 diabetes (T2D) is increasing and has become a major public health concern in many industrialized countries. Despite intense research, best strategies to treat/prevent these costly diseases are still under investigation. However, it is now widely recognized that AD and T2D share many pathophysiological features including increased oxidative stress and amyloid aggregation. 1-4)Amyloid β (Aβ) is the component of the amyloid deposits in the AD brain, 5) while the component of the amyloidogenic peptide deposit in the diabetic pancreatic islets of Langerhans is identified as islet amyloid polypeptide (IAPP), a 37-amino acid peptide. 6,7) Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-β-spine.8) Extensive studies in the past years have found that, similar to Aβ 1-42 , IAPP forms early intermediate assemblies as spherical oligomers 9,10) that are recognized by soluble Aβ oligomers antibody, 11) implicating that these oligomers possess a common folding pattern or conformation.4) The similarities in Aβ 1-42 and IAPP oligomers can be used to investigate the prevention of oxidative stress and amyloid aggregation inhibition related to AD and T2D, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, 12-16) may play a key role inhibiting the aggregation of human IAPP (hIAPP) in case of patients with diabetes.The powerful antioxidant activity of the medicinal halophyte Tamarix gallica L. has been reported as exhibiting a remarkable spectrum of biochemical and pharmacological activities. Although traditionally used for the treatment of various liver disorders and marketed as a herbal medicine in many countries, [17][18][19] there have been no reports on the use of this plant for the treatment or prevention of AD or T2D. Therefore, the aim of this research is to investigate the protective effect of T. gallica towards both disturbances by isolation and identification of the Aβ and hIAPP aggregation inhibitors with antioxidant potential. MATERIALS AND METHODS MaterialsThe aerial par...

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