2. Academic Validation
  3. Gastrodin regulates H3K14la through the CDT2-KAT2A axis to treat Sepsis-induced myocardial dysfunction

Gastrodin regulates H3K14la through the CDT2-KAT2A axis to treat Sepsis-induced myocardial dysfunction

  • Int Immunopharmacol. 2025 Aug 28:161:115065. doi: 10.1016/j.intimp.2025.115065.
Huiming Yu 1,  Qianqian Du 2,  Jiaqin Wu 3,  Fan Feng 4,  Shuwan Hou 5,  Minfu Liu 6,  Sixiang Wang 7,  Xianqiong Liu 8,  Chunli Wang 9,  Kang Xu 10
Affiliations

Affiliations

  • 1 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: huimingyu1213@stmail.hbucm.edu.cn.
  • 2 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: qianqiandu610@stmail.hbucm.edu.cn.
  • 3 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: jiaqin_wu@cqu.edu.cn.
  • 4 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: ffan2024@hbucm.edu.cn.
  • 5 School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: shuwanhou222@stmail.hbucm.edu.cn.
  • 6 School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China. Electronic address: 2432800029@stmail.hbucm.edu.cn.
  • 7 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Ningbo Rehabilitation Hospital, Wenzhou Medical University, Ningbo 315040, China.
  • 8 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430065, China. Electronic address: 1424@hbucm.edu.cn.
  • 9 School of Laboratory Medicine, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430065, China. Electronic address: lilywang@hbucm.edu.cn.
  • 10 Hubei Provincial Engineering Technology Research Center for Chinese Medicine Processing, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, China; Hubei Shizhen Laboratory, Wuhan 430065, China. Electronic address: kangxu05@hbucm.edu.cn.
PMID: 40532326 DOI: 10.1016/j.intimp.2025.115065
Abstract

Sepsis-induced myocardial dysfunction (SIMD), a life-threatening complication of systemic Infection, lacks effective therapies. This study investigated whether Gastrodin (GAS) alleviates SIMD by modulating ubiquitination and histone lactylation pathways. Using an in vivo lipopolysaccharide (LPS)-induced murine model and in vitro TNF-α-stimulated human cardiomyocytes (AC16), we evaluated the effects of GAS on myocardial injury, inflammation, and Apoptosis. GAS treatment significantly reduced myocardial damage, serum cardiac injury markers (cTnT, CK-MB), and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in mice. Transcriptomic analysis also enriched for inflammatory and apoptotic pathways. In vitro, GAS protected AC16 cells from TNF-α-induced Apoptosis and suppressed glycolysis-derived lactate accumulation. Mechanistically, GAS enhanced CDT2-KAT2A binding, promoting ubiquitin-mediated KAT2A degradation, which reduced histone H3 lysine 14 lactylation (H3K14la) and restored energy metabolism. Multi-omics integration confirmed the role of GAS in glycolytic inhibition and lactylation modulation. These findings demonstrated that GAS ameliorates SIMD by targeting the CDT2-KAT2A axis to regulate ubiquitination-lactylation, providing novel therapeutic insights for septic cardiomyopathy.

Keywords

Gastrodin; H3K14la; Lactylation; Sepsis-induced myocardial dysfunction; Ubiquitination.

Figures
Products