从传统中药丹参中提取的抗炎倍半萜：通过抑制 LPS 诱导的 Raw264.7 细胞中的 NF-κB 和 Erk1/2 信号通路来调节促炎介质。
Anti-inflammatory sesquiterpenoids from the Traditional Chinese Medicine Salvia plebeia: Regulates pro-inflammatory mediators through inhibition of NF-κB and Erk1/2 signaling pathways in LPS-induced Raw264.7 cells.
机构信息
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, China.
Key Laboratory of Tropical Plant Resource and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Menglun, Yunnan 666303, China.
出版信息
J Ethnopharmacol. 2018 Jan 10;210:95-106. doi: 10.1016/j.jep.2017.08.034. Epub 2017 Aug 26.
ETHNOPHARMACOLOGICAL RELEVANCE
Salvia plebeia R. Brown, a traditional Chinese medicinal herb, has been used to treat inflammatory diseases such as cough, hepatitis, and diarrhea for a long history.
AIM OF THE STUDY
The aim of the present study was to isolate and identify potential anti-inflammatory agents from the herb of S. plebeia, which may have contributed to its folk pharmacological use in the treatment of inflammatory diseases.
MATERIAL AND METHODS
The aerial parts of S. plebeia were extracted with 95% ethanol and separated by silica gel, RP-C, Sephadex LH-20, and HPLC. The structures of the isolated compounds were elucidated by extensive spectroscopic analysis (MS, NMR, and X-ray). Anti-inflammatory activities of all compounds were evaluated by the model of LPS-induced up-regulated of NO in Raw264.7 macrophages. The expression levels of cytokine (TNF-α) and proteins (iNOS and COX-2) were assessed by ELISA kit and Western blotting analysis, respectively. Furthermore, the influences of salviplenoid A (1) on NF-κB and MAPK signaling pathways were determined by Western blotting analysis and immunofluorescence assay.
RESULTS
Six new (1-6, salviplenoids A-F) and ten known (7-16) sesquiterpenoids were isolated from the herb of S. plebeia. The absolute configurations of compounds 1, 2, and 7 were determined by X-ray diffraction. The new eudesmane-type sesquiterpenoid, salviplenoid A (1), significantly decreased the release of NO and TNF-α and the expression of proteins iNOS and COX-2. In addition, the biochemical mechanistic study indicated that 1 regulated the NF-κB dependent transcriptional activity through inhibiting the nuclear translocation of p50/p65 dimer and decreasing the phosphorylation of IκB and Erk1/2.
CONCLUSIONS
Among all sesquiterpenoids isolated from S. plebeian, the new salviplenoid A (1) exhibited the most potent anti-inflammatory activity in LPS-induced Raw264.7 cells via inhibition of NF-κB and Erk1/2 signaling pathways.
民族药理学相关性
丹参，一种传统的中药草药，长期以来一直被用于治疗咳嗽、肝炎和腹泻等炎症性疾病。
研究目的
本研究旨在从丹参草中分离和鉴定潜在的抗炎剂，这些物质可能有助于其在治疗炎症性疾病方面的民间药理学应用。
材料和方法
丹参的地上部分用 95%乙醇提取，然后用硅胶、反相 C、葡聚糖 LH-20 和高效液相色谱进行分离。通过广泛的光谱分析（MS、NMR 和 X 射线）阐明分离化合物的结构。通过 LPS 诱导的 Raw264.7 巨噬细胞中 NO 上调模型评价所有化合物的抗炎活性。通过 ELISA 试剂盒和 Western blotting 分析分别评估细胞因子（TNF-α）和蛋白质（iNOS 和 COX-2）的表达水平。此外，通过 Western blotting 分析和免疫荧光测定法确定了 salviplenoid A（1）对 NF-κB 和 MAPK 信号通路的影响。
结果
从丹参草中分离得到 6 个新的（1-6，salviplenoids A-F）和 10 个已知的（7-16）倍半萜。通过 X 射线衍射确定了化合物 1、2 和 7 的绝对构型。新的 eudesmane 型倍半萜，salviplenoid A（1），显著降低了 NO 和 TNF-α的释放以及蛋白质 iNOS 和 COX-2 的表达。此外，生化机制研究表明，1 通过抑制 p50/p65 二聚体的核转位和减少 IκB 和 Erk1/2 的磷酸化来调节 NF-κB 依赖性转录活性。
结论
在从丹参中分离得到的所有倍半萜中，新型 salviplenoid A（1）通过抑制 NF-κB 和 Erk1/2 信号通路，在 LPS 诱导的 Raw264.7 细胞中表现出最强的抗炎活性。
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