M10, a Myricetin-3-O-b-D-Lactose Sodium Salt, Prevents Ulcerative Colitis Through Inhibiting Necroptosis in Mice.
M10, a Myricetin-3-O-b-D-Lactose Sodium Salt, Prevents Ulcerative Colitis Through Inhibiting Necroptosis in Mice.
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M10 是一种杨梅素-3-O-b-D-乳糖钠盐，通过抑制小鼠坏死性凋亡来预防溃疡性结肠炎
DOI：
10.3389/fphar.2020.557312
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发表时间：
2020
影响因子：
5.6
通讯作者：
Cui SX
中科院分区：
文献类型：
--
作者：
Zhou XL;Yang J;Qu XJ;Meng J;Miao RR;Cui SX
Background M10 is a derivative of Myricetin by adding a hydrophilic glycosylation group. Our previous study revealed that M10 by oral administration prevented colitis-associated colonic cancer (CAC) through attenuating endoplasmic reticulum stress in mice. In current study, we evaluated the inhibitory effects of M10 on ulcerative colitis in mice model, the mechanism of M10 in preventing colitis was further investigated. Methods Mice model of ulcerative colitis was induced by continuous oral dextran sodium sulfate (DSS). M10 was given gavage once a day for 12 consecutive weeks. Disease activity index (DAI) was recorded by analyzing the symptoms of colitis. Intestinal barrier was analyzed by the Immunofluorescence staining assay. The structure of microvilli of intestinal epithelial cells was analyzed under Transmission electron microscopy (TEM). TEM assay was also performed to determine the formation of necroptosis in the colonic epithelium with ulcerative colitis. We performed Western blotting assay to analyze the IL-6 and NF-κB pathways, as well as the cytokine cascades related to TNF-α signaling pathway during necroptosis. Results M10 by oral administration demonstrated a prevention of ulcerative colitis, showing a significant decrease of DAI as compared to the model mice. Pathological analysis indicated that M10 attenuated the degree of colonic inflammation in colonic tissues. M10 restored the structures of intestinal barrier damaged by DSS. M10 prevented the activation of the IL-6 and NF-κB signaling pathways in the inflamed colonic epithelium. Further, M10 prevented necroptosis in the inflamed colonic mucosal cells through down-regulating the TNF-α pathway. Importantly, M10 demonstrated higher activities in preventing ulcerative colitis than Myricetin and control drug Mesalazine. Conclusions Myricetin derivative M10 prevents chronic ulcerative colitis through inhibiting necroptosis. M10 could be developed as a promising drug for the treatment of chronic ulcerative colitis.
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影响因子：
6
作者：
Burrello, Claudia;Giuffre, Maria Rita;Facciotti, Federica
通讯作者：
Facciotti, Federica
溃疡性结肠炎。
DOI：
10.1016/s0140-6736(16)32126-2
发表时间：
2017-04-29
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ungaro R;Mehandru S;Allen PB;Peyrin-Biroulet L;Colombel JF
通讯作者：
Colombel JF
DOI：
10.1515/jbcpp-2018-0036
发表时间：
2019-01-01
影响因子：
--
作者：
Tatiya-aphiradee, Nitima;Chatuphonprasert, Waranya;Jarukamjorn, Kanokwan
通讯作者：
Jarukamjorn, Kanokwan
影响因子：
3.1
作者：
Tan, Yue;Guan, Yadi;Zheng, Changqing
通讯作者：
Zheng, Changqing
影响因子：
14.8
作者：
Degterev, A;Huang, ZH;Yuan, JY
通讯作者：
Yuan, JY