The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b–9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels–Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC₅₀ values of 6.05 ± 1.10 and 3.81 ± 0.10 μM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots.

中文翻译：

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来自胡椒根 (Piper nigrum L.) 的新型双酰胺生物碱对映体具有乙酰胆碱酯酶抑制和抗神经炎症作用

黑胡椒 ( Piper nigrum L. )的根是一种用于烹调各种肉汤的调味料，以其高营养含量和潜在的药用价值而闻名。在这项研究中，使用分子网络分析策略从辣椒根中分离出九对新型环己烯型双酰胺生物碱 ( 1a / 1b–9a / 9b )。它们的结构是通过广泛的光谱数据、电子圆二色性 (ECD) 计算和 X 射线衍射分析确定的。使用分子间 Diels-Alder 反应，开发了一种从不同单体酰胺生物碱合成双酰胺生物碱的策略。此外，这些化合物首次被手性分离，化合物3a和5a / 5b在脂多糖（LPS）诱导的BV2小胶质细胞模型中显示出显着的抗神经炎症作用。同时，化合物6b和7a显示出对乙酰胆碱酯酶的浓度依赖性抑制活性，IC ₅₀值分别为 6.05 ± 1.10 和 3.81 ± 0.10 μM。这些发现证实，这些双酰胺生物碱可应用于功能性食品配方和药品，并促进辣椒根的进一步开发和利用。