School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210046, China.
Department of Gastroenterology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, 215600, China.
J Ethnopharmacol. 2022 Sep 15;295:115401. doi: 10.1016/j.jep.2022.115401. Epub 2022 May 24.
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.
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.
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.
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.
This study confirmed that the SLRF of ALDE exerted protective activity against UC by regulating the Nrf2-Hmox-1, NF-κB, and MAPK pathways.
冬凌草（ALDE）是菊科植物云木香的统称，传统上被证明具有通过调节气、温寒、缓解胃痛和缓解肠泻来缓解抑郁的功效。因此，ALDE 一直被推荐作为治疗胃肠功能障碍的草药。
本研究旨在探讨冬凌草提取物的倍半萜内酯丰富部分（SLRF）在体内和体外的治疗潜力和作用机制。
制备了冬凌草的水提物（AE）和 SLRF，并通过高效液相色谱法（HPLC）定量分析了主要成分的含量。采用葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠评价提取物的治疗效果。记录体重、疾病活动指数（DAI）和结肠长度，并通过苏木精和伊红（H&E）染色描述结肠的组织病理学变化。通过定量蛋白质组学分析研究了冬凌草中的两种主要倍半萜内酯（木香烃内酯和去氢木香内酯）的体外抗炎活性和可能机制。最后，基于生物信息学分析，我们使用聚合酶链反应（PCR）、免疫荧光和 Western blot 实验验证了提取物在 C57BL/6 小鼠中的抗炎机制。
冬凌草的 SLRF 显著改善了 UC 的病理症状和炎症病理学，而 AE 则具有较弱的保护作用。在脂多糖（LPS）刺激的 RAW264.7 细胞中，木香烃内酯和去氢木香内酯显著降低了白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α的 mRNA 水平，表明这两种倍半萜内酯具有很强的抗炎活性。定量蛋白质组学结果表明，这些内酯的抗炎机制与 NF-κB/MAPK 和 Nrf2-Hmox-1 途径有关。这些结果在 SLRF 治疗的小鼠中得到了进一步验证。
本研究证实，冬凌草的 SLRF 通过调节 Nrf2-Hmox-1、NF-κB 和 MAPK 途径对 UC 发挥保护作用。
