Fattahian Maryam, Ghanadian Mustafa, Zolfaghari Behzad, Aghaei Mahmoud, Zulfiqar Fazila, Khan Ikhlas A, Ali Zulfiqar
School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746, Iran.
School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746, Iran.
Phytochemistry. 2022 Nov;203:113411. doi: 10.1016/j.phytochem.2022.113411. Epub 2022 Aug 28.
Phytochemical investigation of the aerial parts of Artemisia kopetdaghensis resulted in the isolation and characterization of three undescribed eudesmane-type sesquiterpene lactones, persianolide A, 4-epi-persianolide A, and 3α,4-epoxypersianolide A, together with three previously described eudesmane-type sesquiterpene lactones, 11-epi-artapshin, 1β,8α-dihydroxy-11α,13-dihydrobalchanin, and 1β-hydroxy-11-epi-colartin. The abundantly obtained 11-epi-artapshin was oxidized to undescribed 11α,13-dihydroeudesma-12,6α-olide-1,8-dione and 8β-hydroxy-11α,13-dihydroeudesma-12,6α-olide-1-one and acetylated to the undescribed 1,8-O-diacetyl-11α,13-dihydroeudesma-12,6α-olide. Structures were elucidated based on extensive spectral data analyses, including 1D and 2D NMR and HRESIMS. The absolute configuration was determined using calculated and experimental ECD spectral data. Compounds were subsequently subjected to the MTT assay to evaluate their cytotoxicity against prostate cancer cells (DU-145 and LNCaP). Related factors associated with the sequence of apoptosis were tested by ELISA, western blotting, and biochemical assay. Results suggested that 11-epi-artapshin hinders the growth of DU-145 cells through mitochondria-mediated apoptosis initiated by stimulation of ROS build-up, ΔΨm depletion, regulation of the Bax/Bcl-2 ratio, and activation of caspase 3, respectively.
对科佩特山蒿地上部分进行植物化学研究，分离并鉴定了三种未描述的桉叶烷型倍半萜内酯，即波斯内酯A、4-表-波斯内酯A和3α,4-环氧波斯内酯A，以及三种先前描述的桉叶烷型倍半萜内酯，即11-表-阿尔塔普辛、1β,8α-二羟基-11α,13-二氢巴尔查宁和1β-羟基-11-表-科拉丁。大量获得的11-表-阿尔塔普辛被氧化为未描述的11α,13-二氢桉叶-12,6α-内酯-1,8-二酮和8β-羟基-11α,13-二氢桉叶-12,6α-内酯-1-酮，并被乙酰化为未描述的1,8-O-二乙酰基-11α,13-二氢桉叶-12,6α-内酯。基于广泛的光谱数据分析，包括一维和二维核磁共振以及高分辨电喷雾电离质谱，阐明了这些化合物的结构。使用计算和实验电子圆二色谱光谱数据确定了绝对构型。随后对化合物进行MTT试验，以评估它们对前列腺癌细胞（DU-145和LNCaP）的细胞毒性。通过酶联免疫吸附测定、蛋白质免疫印迹和生化分析测试了与凋亡序列相关的相关因素。结果表明，11-表-阿尔塔普辛通过分别由活性氧积累、线粒体膜电位耗竭、Bax/Bcl-2比值调节和半胱天冬酶3激活引发的线粒体介导的凋亡来阻碍DU-145细胞的生长。
