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Molecules 2017, 22(6), 951; doi:10.3390/molecules22060951

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

College of Life and Health Sciences, Northeastern University, Shenyang 110819, China
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Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 22 May 2017 / Revised: 5 June 2017 / Accepted: 5 June 2017 / Published: 8 June 2017
(This article belongs to the Section Medicinal Chemistry)
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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. View Full-Text
Keywords: alisol F; 25-anhydroalisol F; RAW 264.7 macrophages; anti-inflammatory; LPS/d-gal-induced acute liver injured mice; NF-κB, MAPKs, STAT3 signaling pathways alisol F; 25-anhydroalisol F; RAW 264.7 macrophages; anti-inflammatory; LPS/d-gal-induced acute liver injured mice; NF-κB, MAPKs, STAT3 signaling pathways
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bi, X.; Wang, P.; Ma, Q.; Han, L.; Wang, X.; Mu, Y.; Guan, P.; Qu, X.; Wang, Z.; Huang, X. 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, 22, 951.

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