Zhang Fengwei, Elsadek Mohamed Farouk, Chaudhry Shafqat Rasul, Altwaijry Nojood, Khan Shamsuddin Sultan, Fatemeh Jafari Seyedeh, Abdul Majid Aman Shah, Oon Chern Ein, Abdul Majid Amin Malik Shah, Efferth Thomas, Asif Muhammad
Department of Cardiovascular Surgery, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, China.
Department of Biochemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia.
Dose Response. 2025 Aug 19;23(3):15593258251367613. doi: 10.1177/15593258251367613. eCollection 2025 Jul-Sep.
The current study investigated angiogenesis-arresting attributes of oleo-gum resin extract and its underlying molecular mechanisms.
Series of , and models were used to assess anti-angiogenic properties.
MTT cell viability experiments showed that oleo-gum resin extract induced moderate cytotoxicity towards EA.hy926 cells (IC = 42 µg/mL). Extract-treated cells showed significant reduction in invasion, migration, and tube formation potential. At the protein level, down-regulation in expression of angiopoietin-1 and -2, Tie-2, MMP-1 and -9, VEGF-A, and VEGFR2 pro-angiogenic proteins was observed in extract-treated EA.hy926 cells. Signalling array data indicated a marked down-regulation of transcription factors, i.e., HIF-1α and WNT (-3.68 ± 5.74 and -6.24 ± 6.50 fold-change). Furthermore, extract treatment diminished vessel-sprouting in 3D spheroids, rat aorta ring, and chick embryo chorioallantoic membrane models. Treatment with extract significantly reduced intracellular ROS and caspases-8 and -9 levels. GC-MS and HPLC analyses of extract indicated the presence of (+)-α-longipinene, isoledene, cedrene and α-elemene. ADMET prediction of detected compounds revealed good intestinal absorption (> 90%) and skin permeability (log Kp < -2.5), making the extract a suitable candidate for the treatment of angiogenesis-associated intestinal and skin disorders.
Overall, these findings suggest that extract exhibits anti-angiogenic properties by down-regulating the VEGF/angiopoietin axis, warranting further investigations in treating angiogenesis-associated diseases.
本研究调查了油胶树脂提取物的血管生成抑制特性及其潜在的分子机制。
使用一系列体外、体内和 ex vivo 模型评估抗血管生成特性。
MTT 细胞活力实验表明，油胶树脂提取物对 EA.hy926 细胞具有中度细胞毒性（IC = 42 µg/mL）。提取物处理的细胞在侵袭、迁移和管形成潜力方面显著降低。在蛋白质水平上，提取物处理的 EA.hy926 细胞中血管生成素 -1 和 -2、Tie-2、MMP-1 和 -9、VEGF-A 和 VEGFR2 促血管生成蛋白的表达下调。信号阵列数据表明转录因子即 HIF-1α 和 WNT 显著下调（-3.68 ± 5.74 和 -6.24 ± 6.50 倍变化）。此外，提取物处理减少了三维球体、大鼠主动脉环和鸡胚绒毛尿囊膜模型中的血管芽生。提取物处理显著降低了细胞内 ROS 以及半胱天冬酶 -8 和 -9 的水平。提取物的 GC-MS 和 HPLC 分析表明存在（+）-α-长叶蒎烯、异丁烯、雪松烯和 α-榄香烯。对检测到的化合物进行的 ADMET 预测显示其具有良好的肠道吸收（> 90%）和皮肤渗透性（log Kp < -2.5），使该提取物成为治疗血管生成相关肠道和皮肤疾病的合适候选物。
总体而言，这些发现表明提取物通过下调 VEGF/血管生成素轴表现出抗血管生成特性，值得进一步研究用于治疗血管生成相关疾病。
