Α‐Solanine Isolated From Solanum Tuberosum L. cv Jayoung Abrogates LPS‐Induced Inflammatory Responses Via NF‐κB Inactivation in RAW 264.7 Macrophages and Endotoxin‐Induced Shock Model in Mice. Issue 10 (11th March 2016)

• Record Type: Journal Article
• Authors: Shin, Ji‐Sun; Lee, Kyoung‐Goo; Lee, Hwi‐Ho; Lee, Hae Jun; An, Hyo‐Jin; Nam, Jung‐Hwan; Jang, Dae Sik; Lee, Kyung‐Tae
• Is Part Of: Journal of cellular biochemistry. Volume 117:Issue 10(2016:Oct.)
• Page Start: 2327
• Page End: 2339
• Publication Date: 2016-03-11
• Subjects: Α‐SOLANINE -- CYTOKINES -- CYCLOOXYGENASE -- NITRIC OXIDE -- NUCLEAR FACTOR‐κB -- SEPSIS; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25530
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: α‐Solanine, a trisaccharide glycoalkaloid, has been reported to possess anti‐cancer effects. In this study, we investigated the anti‐inflammatory effects of α‐solanine isolated from "Jayoung" a dark purple‐fleshed potato by examining its in vitro inhibitory effects on inducible nitric‐oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), and pro‐inflammatory cytokines in LPS‐induced RAW 264.7 macrophages and its in vivo effects on LPS‐induced septic shock in a mouse model. α‐Solanine suppressed the expression of iNOS and COX‐2 both at protein and mRNA levels and consequently inhibited nitric oxide (NO) and prostaglandin E2 (PGE2 ) production in LPS‐induced RAW 264.7 macrophages. α‐Solanine also reduced the production and mRNA expression of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β) induced by LPS. Furthermore, molecular mechanism studies indicated that α‐solanine inhibited LPS‐induced activation of nuclear factor‐κB (NF‐κB) by reducing nuclear translocation of p65, degradation of inhibitory κBα (IκBα), and phosphorylation of IκB kinaseα/β (IKKα/β). In an in vivo experiment of LPS‐induced endotoxemia, treatment with α‐solanine suppressed mRNA expressions of iNOS, COX‐2, IL‐6, TNF‐α, and IL‐1β, and the activation of NF‐κB in liver. Importantly, α‐solanine increased the survival rate of mice in LPS‐induced endotoxemia and polymicrobial sepsis models. Taken together, our data suggest that the α‐solanine may be a promising therapeutic against inflammatory diseases by inhibiting the NF‐κB signaling pathway. J. Cell. Biochem. 117: 2327–2339, 2016. © 2016 Wiley Periodicals, Inc. Abstract : First, α‐solanine had anti‐inflammatory activity via the regulation of pro‐inflammatory cytokines in an LPS‐induced systemic inflammation mouse model and in RAW 264.7 macrophages. Second, we provided direct in vivo evidence of the ability of α‐solanine to prevent mice from lethal endotoxic shock in LPS‐induced and polymicrobial‐induced sepsis. Third, the anti‐inflammatory properties of α‐solanine were mediated by the down‐regulation of NF‐κB activation signaling in RAW 264.7 macrophages as well as in septic mice.