Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Int J Med Mushrooms. 2021;23(7):13-26. doi: 10.1615/IntJMedMushrooms.2021038850.
The incidence of inflammatory bowel disease (IBD) has continued to increase worldwide, and a caspase-in-dependent, proinflammatory form of programmed cell death termed necroptosis has been observed to actively play an important role in its pathogenesis. Recent studies have indicated that polysaccharides from edible mushrooms suppress colitis. However, there is a lack of information on the effect of mushroom polysaccharides on colitis-associated necroptosis. In this study, the anti-inflammatory activity of polysaccharides from Lentinus edodes and their impact on colitis-associated necroptosis was investigated using both in vivo and in vitro models. Polysaccharides extracted from L. edodes were administered to mice with dextran sodium sulphate-induced colitis prior to and during colitis induction. The Caco-2 cell model of necroptosis was used to investigate the antinecroptotic activity of the polysaccharide sample in an in vitro system. We found that polysaccharides from L. edodes suppressed colitis in mice in a dose-dependent manner and inhibited necroptotic cell death in Caco-2 cells. Interestingly, the polysaccharide extract exerted a remarkable inhibitory effect on the receptor-interacting protein kinase RIPK1-RIPK3-MLKL (mixed lineage kinase domain-like pseudokinase) necroptosis signaling cascade, which resulted in a decreased level of phosphorylated MLKL in the colon of mice with colitis. Notably, the anti-inflammatory and antinecroptotic activities of the polysaccharide sample were found to be dependent on the carbohydrate-rich fraction of the polysaccharides. These results suggested that the inhibitory effect of the polysaccharides from L. edodes on necroptotic cell death in the colon may be partly responsible for its anti-inflammatory activity against ulcerative colitis. Therefore, this study provides evidence for the antinecroptotic and anti-inflammatory activity of L. edodes polysaccharide extract to support its use as an alternative source of therapeutic agent against ulcerative colitis.
炎症性肠病（IBD）的发病率在全球范围内持续上升，一种被称为坏死性凋亡的 caspase 依赖性、促炎形式的程序性细胞死亡已被观察到在其发病机制中发挥重要作用。最近的研究表明，食用蘑菇多糖可抑制结肠炎。然而，关于蘑菇多糖对结肠炎相关坏死性凋亡的影响的信息还很缺乏。在这项研究中，使用体内和体外模型研究了香菇多糖的抗炎活性及其对结肠炎相关坏死性凋亡的影响。在结肠炎诱导前和诱导期间，将从香菇中提取的多糖给予葡聚糖硫酸钠诱导的结肠炎小鼠。在体外系统中，使用 Caco-2 细胞坏死性凋亡模型来研究多糖样品的抗坏死性凋亡活性。我们发现，香菇多糖可剂量依赖性地抑制结肠炎小鼠的结肠炎，并抑制 Caco-2 细胞的坏死性凋亡细胞死亡。有趣的是，多糖提取物对受体相互作用蛋白激酶 RIPK1-RIPK3-MLKL（混合谱系激酶结构域样假激酶）坏死性凋亡信号级联表现出显著的抑制作用，导致结肠炎小鼠结肠中磷酸化 MLKL 水平降低。值得注意的是，多糖样品的抗炎和抗坏死性凋亡活性被发现依赖于多糖的碳水化合物丰富部分。这些结果表明，香菇多糖对结肠中坏死性凋亡细胞死亡的抑制作用可能部分归因于其对溃疡性结肠炎的抗炎活性。因此，本研究为香菇多糖提取物的抗坏死性凋亡和抗炎活性提供了证据，支持其作为治疗溃疡性结肠炎的替代治疗药物来源。
