Dong Wan, Xian Yang, Yuan Wang, Huifeng Zhu, Tao Wang, Zhiqiang Liu, Shan Feng, Ya Fu, Hongli Wang, Jinghuan Wang, Lei Qin, Li Zou, Hongyi Qi
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Pharmacy, The Seventh People's Hospital of Chengdu, Chengdu 610041, China.
J Ethnopharmacol. 2016 Sep 15;191:169-179. doi: 10.1016/j.jep.2016.06.030. Epub 2016 Jun 11.
Catalpol is the main active component of the radix from Rehmannia glutinosa Libosch, which has pleiotropic protective effects in neurodegenerative diseases, ischemic stroke, metabolic disorders and others
Catalpol has been shown to have neuroprotective, neurorepair, and angiogenesis effects following ischemic brain injury. However, its molecular mechanisms are still poorly understood. In previous studies, the JAK2/STAT3 signaling pathway was found to play a role in neuroprotection and angiogenesis. This study investigated the role of catalpol in stimulating angiogenesis via the JAK2/STAT3 pathway after permanent focal cerebral ischemia (pMCAO).
Rats were subjected to right middle cerebral artery occlusion through electrocoagulation and were treated with catalpol (5mg/kg), AG490 was also used to inhibit STAT3 phosphorylation (pSTAT3).
Following stroke, Catalpol improved the neuroethology deficit, increased the cerebral blood flow (CBF) of infarcted brain and upregulated EPO and EPOR. AG490 suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), ultimately inhibited VEGF mRNA expression, which reduced VEGF protein expression and inhibited stroke-induced angiogenesis. However, Catalpol enhanced stroke-induced STAT3 activation and subsequently restored STAT3 activity through the recovery of STAT3 binding to VEGF. Moreover, Catalpol reversed the effect of AG490 on STAT3 activation and nuclear translocation, restored the transcriptional activity of the VEGF promoter by recruiting STAT3 to the VEGF promoter, improved VEGF mRNA and protein expression, increased angiogenesis, reduced the difference in CBF between the infarcted and intact brain and ameliorated the neuroethology behaviors after stroke.
Catalpol affects neuroprotection and angiogenesis via the JAK2/STAT3 signaling pathway, which is mediated by STAT3 activation and VEGF expression. Catalpol may be used as a potential therapeutic drug for stroke.
梓醇是地黄根的主要活性成分，在神经退行性疾病、缺血性中风、代谢紊乱等方面具有多效性保护作用。
梓醇已被证明在缺血性脑损伤后具有神经保护、神经修复和血管生成作用。然而，其分子机制仍知之甚少。在先前的研究中，发现JAK2/STAT3信号通路在神经保护和血管生成中发挥作用。本研究探讨梓醇在永久性局灶性脑缺血（pMCAO）后通过JAK2/STAT3途径刺激血管生成的作用。
通过电凝法使大鼠右侧大脑中动脉闭塞，并用梓醇（5mg/kg）进行治疗，AG490也用于抑制STAT3磷酸化（pSTAT3）。
中风后，梓醇改善了神经行为学缺陷，增加了梗死脑区的脑血流量（CBF），并上调了EPO和EPOR。AG490抑制信号转导和转录激活因子3（STAT3）的磷酸化，最终抑制VEGF mRNA表达，从而降低VEGF蛋白表达并抑制中风诱导的血管生成。然而，梓醇增强了中风诱导的STAT3激活，并随后通过恢复STAT3与VEGF的结合来恢复STAT3活性。此外，梓醇逆转了AG490对STAT3激活和核转位的影响，通过将STAT3募集到VEGF启动子来恢复VEGF启动子的转录活性，改善VEGF mRNA和蛋白表达，增加血管生成，减少梗死脑区与完整脑区之间的CBF差异，并改善中风后的神经行为学表现。
梓醇通过JAK2/STAT3信号通路影响神经保护和血管生成，这是由STAT3激活和VEGF表达介导的。梓醇可能用作中风的潜在治疗药物。
