Anti-inflammatory Eudesmane Sesquiterpenoids from <i>Artemisia hedinii</i>

Fourteen new eudesmane sesquiterpenoids (1, 3–5, 7–16) and seven known analogues were isolated from the whole plant of Artemisia hedinii. Their structures were elucidated by spectroscopic data analysis and comparison with published NMR data, and their absolute configurations were confirmed by X-ray diffraction experiments and TDDFT ECD calculation. Compounds 1–15 were identified as eudesmane acids, which represent a kind of lactone ring-opening eudesmane-type sesquiterpenes with an acetoxyl or a hydroxy group attached to C-9. Compounds 1 and 2, 5 and 6, and 7 and 8 are three pairs of epimers isomerized at C-3, C-5, and C-11, respectively. Compounds 1–9, 11–13, 15–19, and 21 could influence the proinflammatory phenotype of the M1 macrophage. Among them, compounds 5, 8, 9, 12, 16, and 19 consistently exhibited anti-inflammatory effects, as evidenced by downregulating classic pro-inflammatory cytokines TNF-α, IL-12, IL-6, and IFN-γ in LPS-induced primary bone marrow derived M1 macrophages.从赫氏蒿（Artemisia hedinii）的全草中分离得到14个新的桉烷型倍半萜（eudesmane sesquiterpenoids，1、3~5、7~16）及7个已知类似物。通过光谱数据分析以及与已发表的核磁共振波谱（NMR）数据比对解析了它们的结构，并通过X射线衍射实验与含时密度泛函理论电子圆二色谱（TDDFT ECD）计算确定了其绝对构型。化合物1~15被鉴定为桉烷酸类，即一类在9位碳（C-9）上连有乙酰氧基或羟基的内酯开环型桉烷倍半萜。化合物1与2、5与6以及7与8分别为在3位碳（C-3）、5位碳（C-5）和11位碳（C-11）处发生异构的三对差向异构体。化合物1~9、11~13、15~19及21可影响M1巨噬细胞（M1 macrophage）的促炎表型。其中，化合物5、8、9、12、16及19可通过下调脂多糖（LPS）诱导的原代骨髓源性M1巨噬细胞中经典促炎细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素12（IL-12）、白细胞介素6（IL-6）及干扰素γ（IFN-γ）的表达，展现出稳定的抗炎活性。