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Sesquiterpene lactones-rich fraction from Aucklandia lappa Decne. alleviates dextran sulfate sodium induced ulcerative colitis through co-regulating MAPK and Nrf2/Hmox-1 signaling pathway

发布时间:1668147369 人气: 来源:

期刊名:Journal of Ethnopharmacology

发表日期:21 May 2022

文章地址:https://doi.org/10.1016/j.jep.2022.115401


ABSTRACT


Ethnopharmacological relevance: Aucklandia lappa Decne. (ALDE) is the general name for Asteraceae plants Yunmuxiang, which has traditionally been proven to have the efficacy in relieving depression by regulating qi,alleviating cold by warming, attenuating pain in stomach and relieving diarrhea in intestines. Therefore, ALDE is

always recommended as an herbal remedy for gastrointestinal dysfunction.


Aim of the study: The purpose of this study was to explore the therapeutic potential and mechanism of action of the sesquiterpene lactone-rich fraction (SLRF) of ALDE extracts in vivo and in vitro.


Materials and methods: An aqueous extract (AE) and SLRF of ALDE were prepared and the contents of the main components were quantified by high performance liquid chromatography (HPLC). The therapeutic effects of the extracts were evaluated in C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC).

Body weight, disease activity index (DAI), and colon length were recorded, and histopathological changes in the colon were characterized using hematoxylin and eosin (H&E) staining. The in vitro anti-inflammatory activity and possible mechanisms of the two main sesquiterpene lactones in ALDE (costunolide and dehydrocostus lactone) were studied by quantitative proteomic analysis. Finally, based on bioinformatic analysis, we used polymerase chain reaction (PCR), immunofluorescence, and western blot experiments to verify the anti-inflammatory mechanism of the extracts in C57BL/6 mice.


Results: The SLRF of ALDE significantly improved the pathological symptoms and inflammatory pathology of UC,whereas the AE had a weak protective effect. In RAW264.7 cells stimulated with lipopolysaccharide (LPS),costunolide and dehydrocostus lactone significantly reduced the mRNA levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)- α , suggesting that these two sesquiterpene lactones had strong anti-inflammatory activity. Quantitative proteomics results indicated that the anti-inflammatory mechanism of these lactones was associated with the NF-κB/MAPK and Nrf2-Hmox-1 pathways. These results were further validated in SLRF-treated mice.


Conclusion: This study confirmed that the SLRF of ALDE exerted protective activity against UC by regulating the Nrf2-Hmox-1, NF-κB, and MAPK pathways.


2. Materials and methods

................

2.2.2. HPLC-UV analysis

COS and DHL (purity >98%) were purchased from Pufei De Biotech Co., Ltd. (Chengdu, China). Chromatographic analysis of ALDE was performed according to the Chinese Pharmacopoeia (2020). In short,appropriate amounts of COS and DHL standards were mixed with methanol to make a mixed solution containing 0.1 mg of COS or DHL per 1 mL methanol, which is the reference solution. The reference solution,AE of ALDE and SLRF of ALDE were injected into the liquid chromatograph.


羟喜树碱 19685-09-7 Hydroxycamptothecin
辣椒素 404-86-4 Capsaicin
冬凌草甲素 28957-04-2 Oridonin

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