Schisandrin A suppresses lipopolysaccharide-induced inflammation and oxidative stress in RAW 264.7 macrophages by suppressing the NF-B, MAPKs and PI3K/Akt pathways and activating Nrf2/HO-1 signaling

被引：103

作者：

Kwon, Da Hye ^{[1
,2
]}

Cha, Hee-Jae ^{[3
]}

Choi, Eun Ok ^{[1
,2
]}

Leem, Sun-Hee ^{[4
]}

Kim, Gi-Young ^{[5
]}

Moon, Sung-Kwon ^{[6
]}

Chang, Young-Chae ^{[7
,8
]}

Yun, Seok-Joong ^{[9
]}

Hwang, Hye Jin ^{[10
]}

Kim, Byung Woo ^{[11
]}

Kim, Wun-Jae ^{[9
]}

Choi, Yung Hyun ^{[1
,2
]}

机构：

[1] Dong Eui Univ, Dept Biochem, Coll Korean Med, 176 Yangjeong Ro, Busan 47227, South Korea

[2] Dong Eui Univ, Antiaging Res Ctr, Busan 47340, South Korea

[3] Kosin Univ, Coll Med, Dept Parasitol & Genet, Busan 49267, South Korea

[4] Dong A Univ, Dept Biol Sci, Coll Nat Sci, Busan 49315, South Korea

[5] Jeju Natl Univ, Dept Marine Life Sci, Immunobiol Lab, Jeju 63243, South Korea

[6] Chung Ang Univ, Coll Biotechnol & Nat Resource, Dept Food & Nutr, Anseong 17546, South Korea

[7] Catholic Univ Daegu, Sch Med, Res Inst Biomed Engn, Daegu 42472, South Korea

[8] Catholic Univ Daegu, Sch Med, Dept Med, Daegu 42472, South Korea

[9] Chungbuk Natl Univ, Coll Med, Dept Urol, Personalized Tumor Engn Res Ctr, Cheongju 28644, South Korea

[10] Dong Eui Univ, Coll Nursing Healthcare Sci & Human Ecol, Dept Food & Nutr, Busan 47340, South Korea

[11] Dong Eui Univ, Coll Engn, Dept Life Sci & Biotechnol, Busan 47340, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2018年 / 41卷 / 01期

关键词：

schisandrin A; macrophages; inflammation; oxidative stress; KAPPA-B; DOWN-REGULATION; HEME OXYGENASE-1; CELLS; LIGNANS; NRF2; SCHIZANDRIN; MEDIATORS; MODULATION; DISEASE;

D O I：

10.3892/ijmm.2017.3209

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Schisandrin A is a bioactive lignan occurring in the fruits of plants of the Schisandra genus that have traditionally been used in Korea for treating various inflammatory diseases. Although the anti-inflammatory and antioxidant effects of lignan analogues similar to schisandrin A have been reported, the underlying molecular mechanisms have remained elusive. In the present study, schisandrin A significantly suppressed the lipopolysaccharide (LPS)-induced production of the key pro-inflammatory mediators nitric oxide (NO) and prostaglandin E-2 by suppressing the expression of inducible NO synthase and cyclooxygenase-2 at the mRNA and protein levels in RAW 264.7 macrophages. Furthermore, schisandrin A was demonstrated to reduce the LPS-induced secretion of pro-inflammatory cytokines, including tumor necrosis factor- and interleukin-1; this was accompanied by a simultaneous decrease in the respective mRNA and protein levels in the macrophages. In addition, the LPS- induced translocation of nuclear factor-B (NF-B), as well as activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3 kinase (PI3K)/Akt pathways were inhibited by schisandrin A. Furthermore, schisandrin A significantly diminished the LPS-stimulated accumulation of intracellular reactive oxygen species, and effectively enhanced the expression of NF erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). These results suggested that schisandrin A has a protective effect against LPS-induced inflammatory and oxidative responses in RAW 264.7 cells by inhibiting the NF-B, MAPK and PI3K/Akt pathways; these effects are mediated, at least in part, by the activation of the Nrf2/HO-1 pathway. Based on these results, it is concluded that schisandrin A may have therapeutic potential for treating inflammatory and oxidative disorders caused by over-activation of macrophages.

引用

页码：264 / 274

页数：11

共 44 条

[1] Schisandrin B shows neuroprotective effect in 6-OHDA-induced Parkinson's disease via inhibiting the negative modulation of miR-34a on Nrf2 pathway [J].