2. Academic Validation
  3. Piceatannol protects against sepsis-induced myocardial dysfunction via direct inhibition of JAK2

Piceatannol protects against sepsis-induced myocardial dysfunction via direct inhibition of JAK2

  • Int Immunopharmacol. 2021 Jul:96:107639. doi: 10.1016/j.intimp.2021.107639.
Lingpeng Xie 1,  Yuting Wu 2,  Chuying Zhou 1,  Zhangbin Tan 3,  Honglin Xu 1,  Guanghong Chen 1,  Hongmei Chen 1,  Guiqiong Huang 4,  Huijie Fan 5,  Lei Gao 6,  Bin Liu 7,  Yingchun Zhou 8
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China.
  • 2 School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China; Department of Traditional Chinese Medicine, Binzhou Medical University Hospital, Binzhou 256603, China.
  • 3 Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510260, China.
  • 4 Department of Internal Medicine, Huizhou Hospital of Guangzhou University of Traditional Chinese Medicine, Huizhou 516000, China.
  • 5 TCM Health Construction Department of Yangjiang People's Hospital, Guangdong Province, Yangjiang 529500, China.
  • 6 School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
  • 7 Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510260, China. Electronic address: [email protected].
  • 8 School of Traditional Chinese Medicine, Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou 510515, China. Electronic address: [email protected].
PMID: 34162128 DOI: 10.1016/j.intimp.2021.107639
Abstract

Sepsis-induced myocardial dysfunction (SIMD) represents one of the serious complications secondary to sepsis, which is a leading cause of the high mortality rate among septic cases. Subsequent cardiomyocyte Apoptosis, together with the uncontrolled inflammatory response, has been suggested to be closely related to SIMD. Piceatannol (PIC) is verified with potent anti-apoptotic and anti-inflammatory effects, but its function and molecular mechanism in SIMD remain unknown so far. This study aimed to explore the potential role and mechanism of action of PIC in resisting SIMD. The interaction of PIC with JAK2 proteins was evaluated by molecular docking, molecular dynamics (MD) simulation and surface plasmon resonance imaging (SPRi). The cecal ligation and puncture-induced septicemia mice and the LPS-stimulated H9C2 cardiomyocytes were prepared as the models in vivo and in vitro, separately. Molecular docking showed that JAK2-PIC complex had the -8.279 kcal/mol binding energy. MD simulations showed that JAK2-PIC binding was stable. SPRi analysis also showed that PIC has a strong binding affinity to JAK2. PIC treatment significantly ameliorated the cardiac function, attenuated the sepsis-induced myocardial loss, and suppressed the myocardial inflammatory responses both in vivo and in vitro. Further detection revealed that PIC inhibited the activation of the JAK2/STAT3 signaling, which was tightly associated with Apoptosis and inflammation. Importantly, pre-incubation with a JAK2 Inhibitor (AG490) partially blocked the cardioprotective effects of PIC. Collectively, the findings demonstrated that PIC restored the impaired cardiac function by attenuating the sepsis-induced Apoptosis and inflammation via suppressing the JAK2/STAT3 pathway both in septic mice and H9C2 cardiomyocytes.

Keywords

Apoptosis; Inflammation; JAK2; Piceatannol; Sepsis-induced myocardial dysfunction.

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