从胡颠毛乌头（Melodinus axillaris）中分离出了四种单萜吲哚生物碱二聚体（MIADs），命名为axidimins A-D（1-4），其具有前所未有的蜜蜂蜜蜂胆固醇-蜜蜂蜜蜂胆固醇型骨架，并鉴定出了12种已知的MIAs。通过对HRESIMS、NMR、ECD计算和DP4 +分析的全面分析，确定了它们的结构。提出了axidimins A-D的可能生物合成途径。体外（in vitro）实验表明，axidimins C和D对HCT116细胞表现出显著的细胞毒性，其IC50值分别为5.3μM和3.9μM。流式细胞术和Western blot分析结果明确表明，axidimins C和D显著诱导HCT116细胞逆G2/M期阻滞和细胞凋亡。借助网络药理学和分子对接研究，全面讨论了axidimins C和D对HCT116细胞的潜在作用机制。随后，通过Western blot和CETSA分析验证了所选择的靶点，证实axidimins C和D通过激活p38 MAPK途径发挥其细胞毒性作用，最终导致HCT116细胞死亡。该研究提供了证据表明，axidimins C和D具有诱导HCT116细胞细胞周期阻滞和细胞凋亡的潜力，并通过调节p38 MAPK信号通路。这些发现为开发抗结直肠癌药物提供了新的视角。版权所有 © 2023 Elsevier Inc.。保留所有权利。

Four monoterpenoid indole alkaloid dimers (MIADs), axidimins A-D (1-4), which possesses unprecedented apidosperma-aspidosperma-type skeletons, along with twelve known MIAs were isolated from Melodinus axillaris. Their structures were established by comprehensive analysis of the HRESIMS, NMR, ECD calculation and DP4 + analysis. A possible biosynthetic pathway for axidimins A-D was proposed. In vitro, axidimins C and D exhibited significant cytotoxicities against HCT116 cells with IC50 values of 5.3 μM and 3.9 μM, respectively. The results obtained from flow cytometry and Western blot analysis clearly demonstrated that axidimins C and D significantly induced a reverse G2/M phase arrest and apoptosis of HCT116 cells. The potential mechanism of axidimins C and D on HCT116 cells were thoroughly discussed through the utilization of network pharmacology and molecular docking research. Subsequently, the selected targets were validated using Western blot and CETSA analysis, confirming that axidimins C and D exert its cytotoxic effects through the activation of the p38 MAPK pathway, ultimately leading to HCT116 cells death. This study provides evidence indicating that axidimins C and D have the potential to induce cell cycle arrest and apoptosis in HCT116 cells by modulating the p38 MAPK signaling pathway. These findings offer a novel perspective for the development of anti-colorectal cancer drugs.Copyright © 2023 Elsevier Inc. All rights reserved.