Anti-Inflammatory Activities and Liver Protection of Alisol F and 25-Anhydroalisol F through the Inhibition of MAPK, STAT3, and NF-κB Activation In Vitro and In Vivo

  • Molecules. 2017 Jun 8;22(6):951. doi: 10.3390/molecules22060951.
Xiaoxu Bi  1 ,  Pu Wang  2 ,  Qingjuan Ma  3 ,  Li Han  4 ,  Xingbo Wang  5 ,  Yu Mu  6 ,  Peipei Guan  7 ,  Xiaodan Qu  8 ,  Zhanyou Wang  9 ,  Xueshi Huang  10
Affiliations
  • 1. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 2. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 3. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 4. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 5. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 6. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 7. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 8. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 9. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
  • 10. College of Life and Health Sciences, Northeastern University, Shenyang 110819, China. [email protected].
PMID: 28594379 DOI: 10.3390/molecules22060951
Abstract

Alisol F and 25-anhydroalisol F isolated from Alisma orientale, were proved to exhibit anti-inflammatory potential in our previous work. In the current study, the anti-inflammatory effects and action mechanisms of alisol F and 25-anhydroalisol F were investigated in vitro. Moreover, the pharmacological effects of alisol F in lipopolysaccharide (LPS)/d-galactosamine (d-gal)-induced acute liver-injured mice were evaluated. The results demonstrated that alisol F and 25-anhydroalisol F could suppress LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), as well as inhibit the mRNA and protein levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2). In addition, we investigated the role of alisol F and 25-anhydroalisol F in mediating mitogen-activated protein kinases (MAPKs), signal transducers, and activators of transcription 3 (STAT3) and nuclear factor κB (NF-κB) pathways involved in the inflammation process of LPS-stimulated RAW 264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-κB signaling pathway, were obviously suppressed in alisol F and 25-anhydroalisol F treated cells. Results obtained from in vitro experiments suggested alisol F obviously improved liver pathological injury by inhibiting the production of TNF-α, IL-1β, and IL-6, and significantly decreasing the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in LPS/d-gal-induced mice. Furthermore, the reduction of phosphorylation of ERK and JNK, as well as suppression of the NF-κB signaling pathway, were also observed in liver tissues of the alisol F-treated mice model. Alisol F and 25-anhydroalisol F may serve as potential leads for development of anti-inflammatory agents for acute liver failure treatment.

Keywords
">d-gal-induced acute liver injured mice; 25-anhydroalisol F; LPS/; NF-κB, MAPKs, STAT3 signaling pathways; RAW 264.7 macrophages; alisol F; anti-inflammatory.
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