Sericic Acid Ameliorates DSS-induced Ulcerative Colitis in Mice by Modulating the NF-κB and Nrf2 Pathways.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1874467215666220928100319

Lifei-Luo, Jingze Zhang, Xinyu Li, Yanru Zhu, Yansheng Wang, Dailin Liu

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引用次数: 3

Abstract

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease. In previous studies, we found extracts from the roots of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils have a therapeutic effect on UC. Furthermore, sericic acid (SA) is a pentacyclic triterpenoid isolated from this plant that is being used for the first time. The purpose of this study was to investigate whether SA has anti-inflammatory and therapeutic effects on UC and its underlying mechanisms.

Methods: In this study, we used a dextran sulfate-induced UC mouse model and lipopolysaccharide (LPS)-induced inflammatory cell model along with an enzyme-linked immunosorbent assay (ELISA) to quantify the abundance of inflammatory factors and oxidative stress factors in tissues and cells. HE staining was used to analyze the therapeutic effect of the drugs on the UC mouse model. The expression levels of oxidative stress-related proteins were detected using immunoblotting and immunohistochemistry. The anti-inflammatory targets of SA were screened using protein chip arrays and verified by immunoblotting.

Results: We found that SA had anti-inflammatory and antioxidant effects in animal and cellular inflammation models. SA inhibited the levels of NO, TNF-α, IL-6, IL-1β, and MDA in tissues and cells and upregulated the expression level of SOD. Animal experiments showed that SA alleviated the shortening of colon length and colon pathological damage caused by DSS. The antiinflammatory targets of SA were screened using protein chip arrays, and SA was found to inhibit proteins related to the NF-κB signaling pathway. Finally, immunoblotting and immunohistochemistry showed that SA downregulated the expression of p-IKKα/β and its downstream protein p-NF-κB, while promoting the expression of Nrf2 and its downstream protein HO-1.

Conclusion: The above results indicated that SA alleviated DSS-induced colitis by inhibiting NF-κB signaling pathway and activating Nrf2 pathway.

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丝胶酸通过调节NF-κB和Nrf2通路改善dss诱导的小鼠溃疡性结肠炎。

背景:溃疡性结肠炎(UC)是一种慢性非特异性炎性肠病。在之前的研究中，我们发现了玫瑰甜变种巨茶(Coll.)的根提取物。et Hemsl)。Rehd。对UC有治疗作用。此外，丝胶酸(SA)是首次从该植物中分离得到的五环三萜化合物。本研究的目的是探讨SA对UC是否具有抗炎和治疗作用及其潜在机制。方法:采用葡聚糖硫酸盐诱导UC小鼠模型和脂多糖(LPS)诱导的炎症细胞模型，采用酶联免疫吸附法(ELISA)定量检测组织细胞中炎症因子和氧化应激因子的丰度。采用HE染色法分析药物对UC小鼠模型的治疗作用。采用免疫印迹和免疫组织化学检测氧化应激相关蛋白的表达水平。采用蛋白芯片阵列筛选SA的抗炎靶点，免疫印迹法对其进行验证。结果:我们发现SA在动物和细胞炎症模型中具有抗炎和抗氧化作用。SA可抑制组织和细胞中NO、TNF-α、IL-6、IL-1β、MDA水平，上调SOD表达水平。动物实验表明，SA可减轻DSS引起的结肠长度缩短和结肠病理损伤。利用蛋白芯片阵列筛选SA的抗炎靶点，发现SA可抑制NF-κB信号通路相关蛋白。免疫印迹和免疫组化结果显示，SA下调p-IKKα/β及其下游蛋白p-NF-κB的表达，促进Nrf2及其下游蛋白HO-1的表达。结论:上述结果提示SA通过抑制NF-κB信号通路、激活Nrf2通路减轻dss诱导的结肠炎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.