Immunomodulatory activity of brown algae Turbinaria ornata derived sulfated polysaccharide on LPS induced systemic inflammation

Immunomodulatory activity of brown algae Turbinaria ornata derived sulfated polysaccharide on LPS induced systemic inflammation
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DOI:
10.1016/j.phymed.2021.153615
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发表时间:
2021-06-18
期刊:
影响因子:
7.9
通讯作者:
Vasanthi, Hannah R.
Vasanthi, Hannah R.
中科院分区:
医学1区
文献类型:
--
作者:
Bhardwaj, Meenakshi;Mani, Sugumar;Vasanthi, Hannah R.

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背景:炎症和氧化应激是多种慢性疾病常见的病理机制。目的:研究褐藻藻硫酸酯多糖(PS)对脂多糖诱导的大鼠全身炎症的免疫调节作用。研究设计与方法:雄性SD大鼠分别给予不同剂量的PS(2.5,5,10 mg/kgbw),1周后,用LPS(10 mg/kg,ip)诱导大鼠全身炎症反应。注射内毒素8h后取出的血液进行血液学分析(WBC、Hct和PLT)。脂多糖诱导24 h后,分离心肌组织,进行生化、分子和组织病理学分析。通过检测血清指标(AST、CK-MB、γGT)、抗氧化指标(LPO、GSH、SOD、GRX)和炎症指标(IL-1β、IL-6、IL-10、NF-kappaB),分析iNOS、PI3K和Akt的可能作用方式,观察PS预治疗的效果。结果:PS预处理后血清AST、CK-MB和γGT水平明显降低。脂多糖显著升高心肌组织中LPO和GRX的水平,而PS预处理显著降低LPO和GRX的水平。在内毒素诱导下,GSH和SOD水平降低,PS的HD可使其接近正常水平。PS还降低了心脏组织中IL6、TRX的mRNA水平,并增加了IL10的水平,证实了其抗炎和抗氧化的效力。此外,PS对心脏组织中IL1β、核因子kappaB、iNOS和pPI3k/pakt的表达有显著的调节作用,证实了PS的免疫调节作用。组织病理学分析也证实,与脂多糖对照组相比,心脏组织的炎症病理有改善的趋势。结论:综上所述,本研究总结了海洋大型藻类沟藻多糖的免疫调节潜力,并抑制了脂多糖诱导的心脏组织全身性炎症,其机制可能与多糖中的葡萄糖和岩藻糖亚单位有关。
Background: Inflammation and oxidative stress are common pathologies in a wide range of chronic diseases. Polysaccharides are known to exhibit antioxidant and anti-inflammatory potential and are suggested to possess immunomodulatory potential.Purpose: Herein, the immunomodulatory activity of a sulfated polysaccharide (PS) separated from a brown marine algae Turbinaria ornata is studied in LPS instigated systemic inflammation in experimental rats.Study design and methods: Male SD rats are pretreated with different doses of PS (2.5, 5, 10 mg/kg bw) for a week followed by inducing systemic inflammation using LPS (10 mg/kg i.p.). Blood withdrawn after 8 h of LPS injection is subjected to hematological analysis (WBC, HCT, and PLT). After 24 h of LPS induction, cardiac tissue was isolated and subjected to biochemical, molecular, and histopathological analysis. Effect of PS pre-treatment (2.5, 5, 10 mg/kg bw) was checked by assessing serum parameters (AST, CK-MB, and gamma GT), antioxidant markers (LPO, GSH, SOD, Grx) and inflammatory markers (IL1 beta, IL6, IL10, NF kappa B), followed by analyzing the iNOS, PI3k and Akt to identify the probable mode of action.Results: Elevated levels of AST, CK-MB, and gamma GT in serum were significantly reduced on PS pretreatment. LPS significantly raised the LPO and Grx levels in heart tissue whereas, PS pre-treatment significantly reduced LPO and Grx levels. GSH and SOD levels were reduced upon LPS induction and were brought to near normal by HD of PS. PS also reduced the mRNA levels of IL6, Trx, and increased IL10 levels in the heart tissue substantiating its anti-inflammatory and antioxidant potency. Further, IL1 beta, NF kappa B, iNOS, and pPI3k/pAkt expressions were significantly modulated by PS in the cardiac tissue substantiating the immunomodulatory effect. A trend of improvement in the inflammatory pathology was also observed in the heart tissue compared to LPS control, as confirmed by histopathology analysis.Conclusion: Altogether, this study concludes the immunomodulatory potential of PS from the marine macroalgae Turbinaria ornata significantly and prevents LPS induced systemic inflammation in the cardiac tissue presumably influenced by the glucopyranose and fucopyranose subunits in the polysaccharide.