Li Guanjun, Li Huiying, Wang Peili, Zhang Xinzhou, Kuang Wenhua, Huang Ling, Zhang Ying, Xiao Wei, Du Qingfeng, Tang Huan, Wang Jigang
Department of Nephrology, Shenzhen key Laboratory of Kidney Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatric, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, 518020, Guangdong, P. R. China.
Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, 523129, China.
Cell Commun Signal. 2025 Feb 5;23(1):65. doi: 10.1186/s12964-024-01958-3.
Acute pneumonia is a kind of widespread inflammatory pathological process. Dihydrocaffeic acid (DA), metabolite of chlorogenic acid, possesses potent pharmacologic activity for the therapy of a wide range of disorders and various biological properties, such as anti-inflammation. Nevertheless, the specific protein targets and potential molecular mechanisms of DA in acute pneumonia are still poorly understood.
To investigate the anti-inflammation effects of DA and its target and its specific mechanisms.
Here, we conducted lipopolysaccharides (LPS)-induced acute pneumonia model mice. Besides, the activity-based protein profiling (ABPP) was performed to explore the potential targets of DA. Furthermore, cellular thermal shift assay (CETSA) and pulldown-western blot assays were used to validate the conclusion.
In this study, we indicated that DA alleviated acute pneumonia in mice and displayed excellent anti-inflammatory efficacy in vivo and in vitro. Besides, we discovered DA binds directly to transaldolase 1(TALDO1) and influenced its enzymatic activity, and identified the specific cysteine sites Cys250. Also we demonstrated that DA reveals anti-inflammation effect through TALDO1 mediated PERK-IκBα-NF-κB pathway in RAW 264.7 cells.
This study provide support for the potential advancement of DA for use as a therapeutic agent for the treatment of acute pneumonia and inflammation-associated diseases.
急性肺炎是一种广泛存在的炎症性病理过程。二氢咖啡酸（DA）是绿原酸的代谢产物，具有治疗多种疾病的强大药理活性和多种生物学特性，如抗炎作用。然而，DA在急性肺炎中的具体蛋白靶点和潜在分子机制仍知之甚少。
研究DA的抗炎作用及其靶点和具体机制。
在此，我们构建了脂多糖（LPS）诱导的急性肺炎模型小鼠。此外，进行了基于活性的蛋白质谱分析（ABPP）以探索DA的潜在靶点。此外，使用细胞热位移分析（CETSA）和下拉式蛋白质印迹分析来验证这一结论。
在本研究中，我们表明DA可减轻小鼠急性肺炎，并在体内和体外均显示出优异的抗炎效果。此外，我们发现DA直接与转醛醇酶1（TALDO1）结合并影响其酶活性，并确定了特定的半胱氨酸位点Cys250。我们还证明DA通过TALDO1介导的PERK-IκBα-NF-κB途径在RAW 264.7细胞中发挥抗炎作用。
本研究为DA作为治疗急性肺炎及炎症相关疾病的治疗药物的潜在进展提供了支持。
