Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 905, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2021.174186
Keywords
Sepsis-induced cardiac dysfunction (SICD); Tubeimoside I; SIRT3; Inflammation; Oxidative stress; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [31400999, 81770479]
- Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJQN201800417]
- Basic Science and Frontier Technology Research Project of Chongqing Science and Technology Commission [cstc2017jcyjAX0330]
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The study found that tubeimoside I (TBM) can alleviate sepsis-induced cardiac dysfunction (SICD) and exerts its effects through SIRT3. Additionally, SIRT3 plays an essential role in the cardioprotective effects of TBM.
Sepsis-induced cardiac dysfunction (SICD) is one of the key complications in sepsis and it is associated with adverse outcomes and increased mortality. There is no effective drug to treat SICD. Previously, we reported that tubeimoside I (TBM) improved survival of septic mice. The aim of this study is to figure out whether TBM ameliorates SICD. Also, SIRT3 was reported to protects against SICD. Our second aim is to confirm whether SIRT3 plays essential roles in TBM's protective effects against SICD. Our results demonstrated that TBM could alleviate SICD and SICD's key pathological factor, inflammation, oxidative stress, and apoptosis were all reduced by TBM. Notably, SICD induced a significant decrease in cardiac SIRT3 expression, while TBM treatment could reverse SIRT3 expression. To clarify whether TBM provides protection via SIRT3, we injected a specific SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) into mice before TBM treatment. Then the cardioprotective effects of TBM were largely abolished by 3-TYP. This suggests that SIRT3 plays an essential role in TBM's cardioprotective effects. In vitro, TBM also protected H9c2 cells against LPS-induced injury, and siSIRT3 diminished these protective effects. Taken together, our results demonstrate that TBM protects against SICD via SIRT3. TBM might be a potential drug candidate for SICD treatment.
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