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

作者：Bi, Xiaoxu; Wang, Pu; Ma, Qingjuan; Han, Li^*; Wang, Xingbo; Mu, Yu; Guan, Peipei; Qu, Xiaodan; Wang, Zhanyou; Huang, Xueshi^*

来源：Molecules, 2017, 22(6): 951.

DOI：10.3390/molecules22060951

• alisol F
• 25-anhydroalisol F
• RAW 264.7 macrophages
• anti-inflammatory
• LPS/D-gal-induced acute liver injured mice
• NF-kappa B
• MAPKs
• STAT3 signaling pathways

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-alpha), and interleukin-1 beta (IL-1 beta), 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 kappa B (NF-kappa B) pathways involved in the inflammation process of LPS-stimulated RAW264.7 cells. The phosphorylation of ERK, JNK, p38, and STAT3, and the NF-kappa B 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-alpha, IL-1 beta, 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-kappa B 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.

• 出版日期2017-6
• 单位东北大学