School of Chinese Materia Medicine and Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, 030619, Shanxi Province, China.
Graduate School, Shanxi University of Chinese Medicine, Jinzhong, 030619, Shanxi Province, China.
J Ethnopharmacol. 2021 Oct 28;279:114394. doi: 10.1016/j.jep.2021.114394. Epub 2021 Jul 7.
Pigeonpea (Cajanus cajan (L.) Millsp) leaves (PL) are widely used for treating avascular necrosis of the femoral head. PL has an ideal effect on bone angiogenesis in patients with hormone-induced avascular necrosis of the femoral head and could promote the repair of blood vessels in the necrotic femoral head. Angiogenesis is beneficial to the treatment of myocardial ischemia. PL can be used to treat ischemic heart disease; however, no studies have examined whether it could protect the myocardium against ischemia injury via promoting angiogenesis.
The present study aimed to investigate whether PL could encourage angiogenesis on hypoxic human umbilical vein endothelial cells (HUVECs) and whether estrogen receptor (ER-α), protein kinase B (Akt), and vascular endothelial growth factor (VEGF) (the ischemia injury salvage kinase pathway, phosphoinositide-3 kinase (PI3K)) are involved in this effect.
A hypoxic HUVEC model was established by culture in the hypoxia incubator. The proliferation ability of HUVECs was determined by the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, the migration rate of HUVECs was inspected by the Transwell method, the tube formation was evaluated by the Matrigel method, and the expression of PI3K, phosphorylated Akt (p-Akt), and VEGF was detected by Western blotting.
The proliferation, migration, and tube formation were promoted by the PL extract on hypoxic HUVECs, and the hypoxia-induced downstream signaling was counteracted, leading to increased expression of PI3K, p-Akt, and VEGF in HUVECs.
The current findings showed that the PL extracts encourage angiogenesis. In addition, the above effects could be mediated via ER-α and PI3K/Akt/VEGF pathways.
木豆(Cajanus cajan(L.)Millsp)叶(PL)广泛用于治疗股骨头缺血性坏死。PL 对激素诱导的股骨头缺血性坏死患者的骨血管生成具有理想的作用,并能促进坏死股骨头内血管的修复。血管生成有利于治疗心肌缺血。PL 可用于治疗缺血性心脏病;然而,尚无研究表明其是否可以通过促进血管生成来保护心肌免受缺血损伤。
本研究旨在探讨 PL 是否可以促进缺氧人脐静脉内皮细胞(HUVEC)的血管生成,以及雌激素受体(ER-α)、蛋白激酶 B(Akt)和血管内皮生长因子(VEGF)(缺血损伤挽救激酶途径、磷酸肌醇 3 激酶(PI3K))是否参与这一作用。
通过在缺氧培养箱中培养建立缺氧 HUVEC 模型。采用 2,3-双(2-甲氧基-4-硝基-5-磺苯基)-2H-四唑-5-羧基苯胺(XTT)法测定 HUVEC 增殖能力,Transwell 法检测 HUVEC 迁移率,Matrigel 法评价管形成,Western blot 法检测 PI3K、磷酸化 Akt(p-Akt)和 VEGF 的表达。
PL 提取物可促进缺氧 HUVEC 的增殖、迁移和管形成,并拮抗缺氧诱导的下游信号,导致 HUVEC 中 PI3K、p-Akt 和 VEGF 的表达增加。
目前的研究结果表明,PL 提取物可促进血管生成。此外,上述作用可能通过 ER-α和 PI3K/Akt/VEGF 途径介导。