More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1–9 and 12–14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression.

据报道，超过 20 种天然产物可调节 PCSK9 介导的胆固醇调节，并且小分子衍生的前蛋白转化酶枯草杆菌蛋白酶/kexin 9 型 (PCSK9) 抑制剂仍在不断开发和鉴定。在此，从Casearia griifolia Vent干果的氯仿可溶提取物中分离出12 种未描述的 clerodane 型二萜（ 1 – 9和12 – 14 ）和两种已知化合物。使用 PCSK9 mRNA 表达监测测定。在未描述的化合物中，两种非对映体生长素 A 和 B（1和2 ）的立体化学通过二维核欧沃豪塞效应光谱 (NOESY) 实验、激发雕刻间接检测实验 (EXSIDE)、质子间距离分析和计算得到了广泛阐明。其中包括量子化学位移计算与 DP4+ 分析相结合。评估所有分离株对 PCSK9 和 IDOL mRNA 表达的抑制活性。在测试的化合物中，化合物3抑制PCSK9和IDOL mRNA表达。