Nauclofficines A and B, two novel monoterpenoid indole alkaloids from the Li folk herb Nauclea officinalis with anti-allergic inflammatory effects on RBL-2H3 cells
文献类型: 外文期刊
作者: Li, Yan-li 1 ; Wang, Ting 1 ; Wang, Hao 1 ; Wang, Qi 1 ; Cai, Cai-Hong 1 ; Zhu, Guo-Peng 4 ; Mei, Wen-Li 1 ; Xu, Feng-Qing 3 ; Dai, Hao-Fu 1 ; Huang, Sheng-Zhuo 1 ;
作者机构: 1.Chinese Acad Trop Agr Sci, Inst Trop Biosci & Biotechnol, Hainan Key Lab Res & Dev Nat Prod Li Folk Med, Haikou 571101, Peoples R China
2.Chinese Acad Trop Agr Sci, Sanya Res Inst, Sanya 572025, Peoples R China
3.Anhui Univ Chinese Med, Anhui Prov Key Lab New Mfg Technol Tradit Chinese, Hefei 230012, Peoples R China
4.Hainan Univ, Sch Hort, Key Lab Qual Regulat Trop Hort Crop Hainan Prov, Haikou 570228, Peoples R China
关键词: Nauclea officinalis; Monoterpenoid indole alkaloid; Li folk medicine; Anti-inflammatory activity; Nauclofficine
期刊名称:JOURNAL OF ETHNOPHARMACOLOGY ( 影响因子:5.4; 五年影响因子:5.4 )
ISSN: 0378-8741
年卷期: 2025 年 344 卷
页码:
收录情况: SCI
摘要: Ethnopharmacological relevance: Nauclea officinalis Pierre ex Pitard, a traditional medicinal plant cherished by the Li ethnic group, is renowned for its potent anti-allergic properties in the clinic, especially in alleviating respiratory inflammations. This plant is now extensively cultivated to harness its valuable extracts for the production of traditional cough syrup. Aim of the study: To identify the active components responsible for its anti-allergic inflammatory properties and to elucidate the underlying mechanisms of action. Method: The structures of the compounds were meticulously elucidated using comprehensive spectroscopic analyses, including IR, UV, NMR, and MS, along with crystallography and ECD calculations. In vitro studies utilized IgE-induced RBL-2H3 cells to assess cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs). Techniques such as the CCK-8 assay, enzyme-linked immunosorbent assay (ELISA), and Western blot (WB) were employed. Additionally, molecular docking methods were used to simulate and analyze the binding interactions of small molecules with their targets. Result: Two novel monoterpene indole alkaloids were isolated: nauclofficine A, characterized by a unique 6/5/5/ 6/5 fused ring system, and nauclofficine B, which features an additional benzene-substituted dioxane moiety. Their structures were meticulously elucidated, and their biosynthetic pathways were hypothesized. Nauclofficine B exhibited significant inhibitory effects on cell degranulation and the release of inflammatory mediators such as histamine, leukotrienes (LTs), and prostaglandins (PGs) in IgE-induced RBL-2H3 cells. Further analysis using Western blot revealed that it significantly modulated the expression of key proteins in the IgE-mediated inflammatory signaling pathway. Molecular docking experiments suggested that its potential multi-target proteins include Lyn, Fc epsilon R, Syk, and p-Gab2, which were subsequently verified. Conclusions: These results suggested that the wood of N. officinalis contains structurally novel alkaloids with antiallergic inflammatory activity. The absolute configuration of the compound was accurately and reliably deduced, and the biosynthetic pathway was reasonably inferred. Their primary mechanism of action involves targeting multiple key proteins in the IgE-mediated inflammatory signaling pathway, including Lyn, Fc epsilon R, Syk, and pGab2.
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