2. Academic Validation
  3. Chemo-proteomics reveals dihydrocaffeic acid exhibits anti-inflammation effects via Transaldolase 1 mediated PERK-NF-κB pathway

Chemo-proteomics reveals dihydrocaffeic acid exhibits anti-inflammation effects via Transaldolase 1 mediated PERK-NF-κB pathway

  • Cell Commun Signal. 2025 Feb 5;23(1):65. doi: 10.1186/s12964-024-01958-3.
Guanjun Li # 1,  Huiying Li # 1 2,  Peili Wang # 1 3,  Xinzhou Zhang # 1,  Wenhua Kuang 1,  Ling Huang 1,  Ying Zhang 4,  Wei Xiao 5 6,  Qingfeng Du 7 8,  Huan Tang 9 10,  Jigang Wang 11 12 13 14 15 16
Affiliations

Affiliations

  • 1 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.
  • 2 Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, 523129, China.
  • 3 National Clinical Research Center for Chinese Medicine Cardiology, Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China.
  • 4 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, P.R. China.
  • 5 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. xw7688@smu.edu.cn.
  • 6 Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China. xw7688@smu.edu.cn.
  • 7 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. dqfsmu7@126.com.
  • 8 School of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China. dqfsmu7@126.com.
  • 9 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. htang@icmm.ac.cn.
  • 10 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, P.R. China. htang@icmm.ac.cn.
  • 11 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. jgwang@icmm.ac.cn.
  • 12 Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan, 523129, China. jgwang@icmm.ac.cn.
  • 13 State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, P.R. China. jgwang@icmm.ac.cn.
  • 14 Center for Drug Research and Development, Guangdong Provincial Key Laboratory for Research and Evaluation of Pharmaceutical Preparations, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China. jgwang@icmm.ac.cn.
  • 15 School of Traditional Chinese Medicine, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China. jgwang@icmm.ac.cn.
  • 16 State Key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, 475004, P.R. China. jgwang@icmm.ac.cn.
  • # Contributed equally.
PMID: 39910568 DOI: 10.1186/s12964-024-01958-3
Abstract

Background: 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.

Purpose: To investigate the anti-inflammation effects of DA and its target and its specific mechanisms.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Activity-based chemical proteomic; Dihydrocaffeic acid; Natural products and herbs; Network pharmacology; Transaldolase 1.

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