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

  • J Cell Biochem. 2016 Oct;117(10):2327-39. doi: 10.1002/jcb.25530.
Ji-Sun Shin  1  2 Kyoung-Goo Lee  1 Hwi-Ho Lee  1  3 Hae Jun Lee  1  3 Hyo-Jin An  4 Jung-Hwan Nam  5 Dae Sik Jang  3 Kyung-Tae Lee  1  3
Affiliations
  • 1. Department of Pharmaceutical Biochemistry, Kyung Hee University, Seoul, Republic of Korea.
  • 2. Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Republic of Korea.
  • 3. Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, Republic of Korea.
  • 4. Department of Pharmacology, College of Oriental Medicine, Sangji University, Wonju-si, Gangwon-do, 220-702, Republic of Korea.
  • 5. Highland Agriculture Research Center, NICS, RDA, Pyeongchang, 232-955, Republic of Korea.
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.

Keywords
CYCLOOXYGENASE; CYTOKINES; NITRIC OXIDE; NUCLEAR FACTOR-κB; SEPSIS; Α-SOLANINE.
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