Low Weight Polysaccharide of Hericium erinaceus Ameliorates Colitis via Inhibiting the NLRP3 Inflammasome Activation in Association with Gut Microbiota Modulation.
Low Weight Polysaccharide of Hericium erinaceus Ameliorates Colitis via Inhibiting the NLRP3 Inflammasome Activation in Association with Gut Microbiota Modulation.
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DOI：
10.3390/nu15030739
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发表时间：
2023-02-01
期刊：
影响因子：
5.9
通讯作者：
Geng Y
中科院分区：
文献类型：
--
作者：
Ren Y;Sun Q;Gao R;Sheng Y;Guan T;Li W;Zhou L;Liu C;Li H;Lu Z;Yu L;Shi J;Xu Z;Xue Y;Geng Y
溃疡性结肠炎（UC）是一种典型的免疫失调性炎症性肠病，目前仍需要高效低毒的新型治疗药物。猴头菌在中国已被广泛用于治疗不同的健康问题，特别是胃肠道疾病数千年。本研究中，我们从黑曲霉菌丝体中分离、纯化并鉴定了一种新型的低分子量多糖（HEP 10，分子量：9.9 kDa）。深层培养的猴头菌。我们探讨了HEP 10对UC的治疗作用及其机制。一方面，HEP 10抑制LPS攻击的鼠巨噬细胞RAW 264. 7细胞以及DSS诱导的结肠炎小鼠结肠中TNF-α、IL-1β、IL-6、诱导型iNOS和考克斯-2的产生。另一方面，HEP 10处理显著抑制NLRP 3炎性体、NF-κB、AKT和MAPK通路的活化。此外，HEP 10通过显著增加嗜粘蛋白阿克曼氏菌并促进肠道微生物群的功能转变来逆转DSS诱导的肠道群落组成和结构的改变。结构方程模型还强调，HEP 10可以通过肠道微生物群广泛变化。因此，HEP 10比H.猴头菌可作为一种新型的膳食补充剂和益生元，用于改善结肠炎。
Ulcerative colitis (UC), one of the typical inflammatory bowel diseases caused by dysregulated immunity, still requires novel therapeutic medicine with high efficacy and low toxicity. Hericium erinaceus has been widely used to treat different health problems especially gastrointestinal sickness in China for thousands of years. Here, we isolated, purified, and characterized a novel low weight polysaccharide (HEP10, Mw: 9.9 kDa) from the mycelia of H. erinaceus in submerged culture. We explored the therapeutic effect of HEP10 on UC and explored its underlying mechanisms. On one hand, HEP10 suppressed the production of TNF-α, IL-1β, IL-6, inducible iNOS, and COX-2 in LPS challenged murine macrophage RAW264.7 cells, as well as in colons from DSS-induced colitis mice. On the other hand, HEP10 treatment markedly suppressed the activation of NLRP3 inflammasome, NF-κB, AKT, and MAPK pathways. Moreover, HEP10 reversed DSS-induced alternation of the gut community composition and structure by significantly increasing Akkermansia muciniphila and also promoting functional shifts in gut microbiota. Structural equation modeling also highlighted that HEP10 can change widely through gut microbiota. In conclusion, HEP10 has a better prebiotic effect than the crude polysaccharides of H. erinaceus, which can be used as a novel dietary supplement and prebiotic to ameliorate colitis.