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皂苷通过 TLR/NF-[Formula: see text]B 和 MAPK 信号通路调节炎症反应并改善类似 IBD 的症状。

Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-[Formula: see text]B and MAPK Signaling Pathways.

机构信息

Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao 999078, P. R. China.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 610000, P. R. China.

出版信息

Am J Chin Med. 2021;49(4):925-939. doi: 10.1142/S0192415X21500440. Epub 2021 Apr 7.

DOI:10.1142/S0192415X21500440
PMID:33829964
Abstract

saponins (PNS) are the main active ingredients of (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.

摘要

总皂苷(PNS)是(Burk)F. H. Chen 的主要活性成分,作为传统中药已有数千年的历史,具有多种临床作用,包括抗炎、抗氧化和心血管保护。炎症性肠病(IBD)是一种复杂的胃肠道炎症性疾病,目前无法完全治愈。分析了 PNS 在葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠模型中的抗炎和保护作用。PNS 抑制了 Pam3CSK4 诱导的 RAW 264.7 巨噬细胞中一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的释放。在动物研究中,与 DSS 诱导的小鼠相比,PNS 降低了结肠组织中促炎细胞因子(TNF-α、IL-6 和 MCP-1)的表达。此外,PNS 治疗导致 DSS 诱导的核因子 kappa-B 激酶抑制剂[Formula: see text]/[Formula: see text](IKK[Formula: see text]/[Formula: see text]、I[Formula: see text]B[Formula: see text]和 p65 的激活显著减少。另一方面,PNS 抑制了 c-Jun N-末端激酶(JNK)、p38 和细胞外调节蛋白激酶 1/2(ERK1/2)的磷酸化。总之,我们的结果表明,PNS 通过下调丝裂原活化蛋白激酶(MAPK)和 NF-[Formula: see text]B 信号通路,对结肠炎小鼠提供了深刻的保护作用,这与减轻炎症反应、减轻组织损伤以及维持肠道完整性和功能有关。

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