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丹参多糖及其相关代谢产物5-甲氧基吲哚-3-甲醛通过调节Nrf2/Keap1信号通路改善实验性结肠炎。

Salvia miltiorrhiza polysaccharide and its related metabolite 5-methoxyindole-3-carboxaldehyde ameliorate experimental colitis by regulating Nrf2/Keap1 signaling pathway.

作者信息

Fu Yu-Ping, Peng Xi, Zhang Chao-Wen, Jiang Quan-Xing, Li Cen-Yu, Paulsen Berit Smestad, Rise Frode, Huang Chao, Feng Bin, Li Li-Xia, Chen Xing-Fu, Jia Ren-Yong, Li Yang-Ping, Zhao Xing-Hong, Ye Gang, Tang Hua-Qiao, Liang Xiao-Xia, Lv Cheng, Tian Meng-Liang, Yin Zhong-Qiong, Zou Yuan-Feng

机构信息

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Section for Pharmaceutical Chemistry, Department of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway.

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Carbohydr Polym. 2023 Apr 15;306:120626. doi: 10.1016/j.carbpol.2023.120626. Epub 2023 Jan 26.

DOI:10.1016/j.carbpol.2023.120626
PMID:
36746576
Abstract

The roots of Salvia miltiorrhiza have been used in Traditional Chinese Medicine for thousands of years. However, tons of aerial parts of this plant are usually discarded in the production of roots preparation. To make better use of these plant resources, the polysaccharide isolated from the aerial part of S. miltiorrhiza was investigated for its potential protection against intestinal diseases. A pectic polysaccharide (SMAP-1) was isolated and characterized being composed of homogalacturonan as the main chain and rhamnogalacturonan type I as ramified region, with side chains including arabinans and possible arabinogalactan type I and II. SMAP-1 exhibited robust protective effects against dextran sodium sulfate (DSS)-induced colitis and restored colitis symptoms, colonic inflammation, and barrier functions. Anti-oxidative effects were also observed by up-regulating Nrf2/Keap1 signaling pathway. Additionally, the level of serum 5-methoxyindole-3-carboxaldehyde (5-MC) was restored by SMAP-1 identified in metabolomic analysis, being correlated with the aforementioned effects. Protection against oxidative stress on intestinal porcine enterocyte cells (IPEC-J2) by 5-MC was observed through the activation of Nrf2/Keap1 system, as also shown by SMAP-1. In conclusion, SMAP-1 could be a promising candidate for colitis prevention, and 5-MC could be the signal metabolite of SMAP-1 in protecting against oxidative stress in the intestine.

摘要

丹参的根在传统中药中已使用了数千年。然而,在制备根制剂的生产过程中,这种植物的大量地上部分通常被丢弃。为了更好地利用这些植物资源,对从丹参地上部分分离得到的多糖进行了研究,以探讨其对肠道疾病的潜在保护作用。分离并鉴定了一种果胶多糖(SMAP-1),其主要由同型半乳糖醛酸聚糖作为主链,鼠李糖半乳糖醛酸聚糖I型作为分支区域组成,侧链包括阿拉伯聚糖以及可能的I型和II型阿拉伯半乳聚糖。SMAP-1对葡聚糖硫酸钠(DSS)诱导的结肠炎表现出强大的保护作用,并恢复了结肠炎症状、结肠炎症和屏障功能。通过上调Nrf2/Keap1信号通路也观察到了抗氧化作用。此外,代谢组学分析鉴定出SMAP-1可使血清5-甲氧基吲哚-3-羧醛(5-MC)水平恢复正常,这与上述作用相关。5-MC通过激活Nrf2/Keap1系统对猪肠上皮细胞(IPEC-J2)的氧化应激具有保护作用,SMAP-1也有此作用。总之,SMAP-1可能是预防结肠炎的一个有前途的候选物,5-MC可能是SMAP-1在保护肠道免受氧化应激中的信号代谢物。

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