Format

Send to

Choose Destination
Int Immunopharmacol. 2017 Aug;49:50-59. doi: 10.1016/j.intimp.2017.05.022. Epub 2017 May 25.

Pterostilbene alleviates polymicrobial sepsis-induced liver injury: Possible role of SIRT1 signaling.

Author information

1
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
2
Department of Physiology, Changzhi Medical College, Changzhi 046000, China.
3
Department of the Second Digestive Internal Medicine, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
4
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: mengfeier82@163.com.
5
Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: lininfection@sina.com.

Abstract

Liver injury occurs frequently during sepsis. Pterostilbene (Pte), a natural dimethylated analog of resveratrol from blueberries, exerts anti-inflammatory and anti-apoptotic effects in various diseases. However, the role of Pte in sepsis-induced liver injury and its underlying mechanisms remain unknown. The current study aimed to evaluate the protective effects of Pte on sepsis-induced liver injury and its potential mechanisms. Sepsis was induced using cecal ligation and puncture (CLP) in C57BL/6 mice. Mice were administered Pte (5, 10, 15mg/kg, i.p.) at 0.5h, 2h, and 8h after CLP induction. The pathological changes of the liver were evaluated using hematoxylin and eosin (H&E) staining. The serum levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL-6), myeloperoxidase (MPO), p38 mitogen-activated protein kinase (p38MAPK), Bax, and B-cell lymphoma 2 (Bcl-2) were also evaluated. Pte treatment attenuated the CLP-induced liver injury, as evidenced by the attenuated histopathologic injuries and the decreased serum aminotransferase levels. Pte reduced the serum inflammatory cytokine (TNF-α and IL-6) levels and hepatic mRNA levels of TNF-α and IL-6. Pte also reduced MPO activity and p38MAPK activation in the liver. Additionally, Pte significantly inhibited Bax expression and increased Bcl-2 expression. Moreover, Pte increased the expression of sirtuin-1 (SIRT1) and reduced the expression of acetylated forkhead box O1 (Ac-FoxO1), acetylated Ac-p53, and acetylated nuclear factor-kappa beta (Ac-NF-κB). However, SIRT1 small interfering RNA (siRNA) abolished Pte's effects on the expression levels of those protein. Notably, Pte improved the survival rate in septic mice. In conclusion, Pte alleviates sepsis-induced liver injury by reducing inflammatory response and inhibiting hepatic apoptosis, and the potential mechanism is associated with SIRT1 signaling activation.

KEYWORDS:

Inflammation; Liver injury; Pterostilbene; SIRT1 signaling; Sepsis

PMID:
28550734
DOI:
10.1016/j.intimp.2017.05.022
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center