a Department of Biochemistry, Faculty of Life Sciences , Aligarh Muslim University , Aligarh , UP 202002 , India.
b Department of Biochemistry , SKIMS Medical College , Srinagar , Jammu and Kashmir , India.
J Biomol Struct Dyn. 2018 Nov;36(14):3791-3802. doi: 10.1080/07391102.2017.1400470. Epub 2017 Nov 30.
Several mammalian proteins form pathological deposits under nonphysiological conditions that are associated with many degenerative diseases. Protein aggregation is associated with aging, as well as a variety of diseases, including cystic fibrosis, amyotrophic lateral sclerosis (ALS), and hypertrophic cardiomyopathy. There is a lack of any potential anti-amyloidogenic agents and therapeutics till date. Polyphenols have been accredited with myriad biological effects. An analysis of the effects of natural agents like baicalin (BC) and gallocatechin (GC) on aggregation process can open new avenues for the treatment of protein misfolding diseases. Thus, investigation of the effects of these flavonoids on Buffalo Heart Cystatin (BHC) aggregation induced by a reactive metabolic dialdehyde, glyoxal (GO), was taken up. Results have shown that elevated concentration of GO forms aggregates of BHC, which was characterized by an increase in the ANS fluorescence intensity, an increase in ThT fluorescence intensity, red shift in Congo red absorbance, negative ellipticity peak at 217 nm in the far-UVCD and BHC aggregates displaying by TEM. Using fluorescence spectroscopic analysis with Thioflavin T, CD and electron microscopic studies, anti-aggregation effects of polyphenols, BC and GC were analyzed. The study showed that BC and GC produced concentration-dependent anti-aggregation effects with GC producing a more pronounced effect than BC. The study proposed a mechanistic approach assuming structural constraints and specific aromatic interactions of polyphenols with sheets of BHC aggregates.
在非生理条件下，几种哺乳动物蛋白会形成病理性沉积物，这些沉积物与许多退行性疾病有关。蛋白聚集与衰老以及包括囊性纤维化、肌萎缩侧索硬化症 (ALS) 和肥厚型心肌病在内的多种疾病有关。到目前为止，还没有任何潜在的抗淀粉样变性药物和疗法。多酚具有多种生物学作用。分析天然物质（如黄芩素 (BC) 和没食子儿茶素 (GC)）对聚集过程的影响，可以为治疗蛋白错误折叠疾病开辟新途径。因此，研究了这些类黄酮对由反应性代谢二醛——乙二醛 (GO) 诱导的水牛心脏半胱氨酸蛋白酶抑制剂 (BHC) 聚集的影响。结果表明，GO 的浓度升高会形成 BHC 的聚集体，这表现为 ANS 荧光强度增加、ThT 荧光强度增加、刚果红吸收红移、远紫外圆二色性中的负椭圆度峰值在 217nm 处和 TEM 显示的 BHC 聚集体。使用噻唑蓝 T、CD 和电子显微镜研究的荧光光谱分析，分析了多酚、BC 和 GC 的抗聚集作用。研究表明，BC 和 GC 产生浓度依赖性的抗聚集作用，GC 产生的作用比 BC 更明显。该研究提出了一种机制方法，假设多酚与 BHC 聚集物片层之间存在结构约束和特定的芳香相互作用。
