School of Chemistry and Environment, College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Zhanjiang 524-088, China.
School of Chemistry and Environment, College of Food Science and Technology, Shenzhen Institute of Guangdong Ocean University, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Zhanjiang 524-088, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhanjiang 524-088, China.
Int Immunopharmacol. 2022 Aug;109:108931. doi: 10.1016/j.intimp.2022.108931. Epub 2022 Jun 12.
Atherosclerosis is a significant cause of many cardiovascular diseases. Oxidized low-density lipoproteins (ox-LDL) are crucial in developing atherosclerosis. In this study, we researched the effects of two alkaloids epi-aszonalenin A (EAA) and aszonalenin (AZN) of an endophytic fungus Aspergillus terreus C23-3 from coral Pavona, on ox-LDL-induced inflammation, apoptosis and angiogenesis in HUVEC, and evaluated related factors and mechanism. The results reveal that EAA and AZN inhibit HUVEC migration, invasion, angiogenesis and reactive oxygen species (ROS) accumulation on a non-cytotoxic basis. Then, EAA and AZN suppressed the ox-LDL-induced of LOX-1, VEGF protein expression, MAPK and PI3K/AKT pathways phosphorylation. Furthermore, AZN suppressed the ox-LDL-induced inflammatory factors (IL-6, IL-1β, and TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and VEGF receptor VEGFR-2 and platelet-derived growth factor PDGF. In addition, it inhibited ox-LDL-induced atherosclerosis by blocking inflammation and apoptosis through nuclear factor κB (NF-κB), cleaved-caspase-3 and Bax/Bcl-2 pathways. Molecular docking results confirm that the effect of AZN on atherosclerosis inhibitory activity may be attributed to hydrogen bonds formed into LOX-1 and VEGFR-2. These data indicate that EAA and AZN can effectively prevent ox-LDL-induced HUVEC damage and angiogenesis by inhibiting inflammation and apoptosis. Therefore, EAA and AZN may have potential beneficial effects in regulating atherosclerosis and plaque angiogenesis.
动脉粥样硬化是许多心血管疾病的重要原因。氧化型低密度脂蛋白（ox-LDL）在动脉粥样硬化的发生发展中起着关键作用。在这项研究中，我们研究了来源于珊瑚 Pavona 的内生真菌 Aspergillus terreus C23-3 的两种生物碱 epi-aszonalenin A（EAA）和 aszonalenin（AZN）对 ox-LDL 诱导的 HUVEC 炎症、凋亡和血管生成的影响，并评估了相关因素和机制。结果表明，EAA 和 AZN 在非细胞毒性基础上抑制 HUVEC 迁移、侵袭、血管生成和活性氧（ROS）积累。然后，EAA 和 AZN 抑制了 ox-LDL 诱导的 LOX-1、VEGF 蛋白表达、MAPK 和 PI3K/AKT 通路磷酸化。此外，AZN 抑制了 ox-LDL 诱导的炎症因子（IL-6、IL-1β 和 TNF-α）、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和 VEGF 受体 VEGFR-2 和血小板衍生生长因子 PDGF。此外，它通过阻断核因子 κB（NF-κB）、裂解 caspase-3 和 Bax/Bcl-2 通路抑制炎症和凋亡，从而抑制 ox-LDL 诱导的动脉粥样硬化。分子对接结果证实，AZN 对动脉粥样硬化抑制活性的影响可能归因于与 LOX-1 和 VEGFR-2 形成的氢键。这些数据表明，EAA 和 AZN 可通过抑制炎症和凋亡，有效预防 ox-LDL 诱导的 HUVEC 损伤和血管生成。因此，EAA 和 AZN 可能在调节动脉粥样硬化和斑块血管生成方面具有潜在的有益作用。
