Bo Pang,Xinyu Bian,Junpeng Xing,Shu Liu,Zhiqiang Liu,Fengrui Song
The abnormal aggregation of human islet amyloid polypeptide (hIAPP) is a crucial pathogenic factor associated with type 2 diabetes (T2D). The development of effective inhibitors to prevent hIAPP aggregation is a common therapeutic strategy against T2D. Lithospermic acid (LA) is a natural compound with diversified biological activities. In this study, electrospray ionization coupled with ion mobility–mass spectrometry, thioflavin T fluorescence assay , Congo red binding assay, Nile red fluorescence assay, circular dichroism spectroscopy, transmission electron microscopy , cell toxicity, lactate dehydrogenase assay (LDH) assay and molecular docking were combined to explore the influence of LA on hIAPP aggregation. Results showed that LA had favorable binding affinity to hIAPP and formed hIAPP–LA complexes, which could alter the relative abundance of the compact and extended conformers and promoted the transition of extended structures to compact conformers. LA also displayed strong inhibitory actions on fibrillation and potential protective effects against hIAPP-induced cell toxicity. Therefore, the obtained results were useful to understand the possible inhibitory mechanism of LA on hIAPP aggregation and provided valuable reference for the screening of potent amyloid inhibitors.
Wei Li,Xinyao Han,Wei Wang,Qingping Du,Mingxun Ai,Shihao Huang,Tongle Sun,Hongji Zeng,Yuhang Li
The present research sought to investigate the impacts of Brassica rapa L. polysaccharide (Brp) on glycolipid metabolism in diabetic rats and the regulatory role of gut microbiota in metabolic balance. After 30-day Brp gavage, glycolipid metabolic parameters and amino acid levels were measured, and gut microbial communities were sequenced and analyzed. The results showed that Brp improved glycolipid metabolism, alleviated insulin resistance and hepatic oxidative stress, increased liver glycogen synthesis, and modulated gut microbiota composition. Specifically, Brp potentially enhanced short-chain fatty acid (SCFAs) production by enriching Blautia and Roseburia populations while reducing lipopolysaccharide (LPS)-producing bacteria to lower pathological risks. Notably, Brp may reduce the risk of T2D by increasing the concentration of lysophosphatidic acid (18:2(9Z,12Z)/0:0), indoleacrylic acid, cholic acid, and betaine, and decreasing high-risk metabolites such as 3,4-dihydroxybutyrate, xanthine, and carnitine, as well as regulating branched-chain amino acids and aromatic amino acids throughout the development of T2D.
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