1. Academic Validation
  2. Protective effects of dioscin against systemic inflammatory response syndromevia adjusting TLR2/MyD88/NF‑κb signal pathway

Protective effects of dioscin against systemic inflammatory response syndromevia adjusting TLR2/MyD88/NF‑κb signal pathway

  • Int Immunopharmacol. 2018 Dec;65:458-469. doi: 10.1016/j.intimp.2018.10.036.
Xuerong Zhao 1 Lianhong Yin 1 Lingling Fang 1 Lina Xu 1 Pengyuan Sun 1 Ming Xu 1 Kexin Liu 1 Jinyong Peng 2
Affiliations

Affiliations

  • 1 College of Pharmacy, Dalian Medical University, Western 9 Lvshun nan Road, Dalian 116044, China.
  • 2 College of Pharmacy, Dalian Medical University, Western 9 Lvshun nan Road, Dalian 116044, China. Electronic address: jinyongpeng2016@dlmedu.edu.cn.
Abstract

Development of active compounds to control inflammation against systemic inflammatory response syndrome (SIRS) is critical important. Dioscin shows anti-inflammatory effects in our previous works. However, the action of the compound on SIRS still remained unknown. In the present paper, zymosan induced generalized inflammation (ZIGI) models in mice and rats, and PMA-differentiated THP‑1 cells stimulated by lipopolysaccharide (LPS) and Pam3-Cys-Ser-Lys4 (Pam3CSK4) were used. The results showed that dioscin significantly inhibited the proliferation of THP‑1 cells stimulated by LPS and Pam3CSK4, obviously reduced the soakage of inflammatory cells and necrosis in liver, kidney and intestine of rats and mice, and reduced peritoneal ascites fluid compared with ZIGI model groups. In addition, dioscin significantly declined the levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA) and myeloperoxidase (MPO), increased the levels of superoxide dismutase (SOD) in rats and mice. The migration of macrophages in tissues was also suppressed by dioscin. Mechanism investigation showed that dioscin significantly inhibited the expression levels of TLR2, MyD88, NF‑κb, HMGB‑1, increased the expression levels of IKBα, and decreased the mRNA levels of interleukin‑1 beta (IL‑1β), interleukin‑6 (IL‑6) and tumor necrosis factor‑alpha (TNF‑α) in liver, kidney, intestine tissues of rats and mice, and in PMA-differentiated THP‑1 cells, which were further confirmed by TLR2 siRNA silencing in vitro. In conclusion, our data confirmed that dioscin exhibited protective effects against SIRS via adjusting TLR2/MyD88 signal pathway, which should be developed as one potent candidate to treat SIRS in the future.

Keywords

Dioscin; Lipopolysaccharide; Pam3CSK4; SIRS; TLR2/MyD88 pathway; Zymosan.

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