Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

doi:10.1007/s13659-021-00322-z

应用天然产物 ›› 2021, Vol. 11 ›› Issue (6): 659-670.DOI: 10.1007/s13659-021-00322-z

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Ya-Juan Chen¹, Chen Chen¹, Meng-Yuan Li¹, Qing-Qing Li¹, Xiu-Juan Zhang¹, Rong Huang¹, Xing-Wei Zhu¹, Chun-Yun Bai¹, Liu-Yi Zhang¹, Pei-Hua Peng², Wei-Min Yang¹

1 School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 Western Chunrong Road, Yuhua Street, Chenggong New City, Kunming 650500, China;
2 Department of Anesthesiology, The First Affiliated Hospital of Kunming University, Kunming 650032, China

收稿日期:2021-09-28 出版日期:2021-12-24 发布日期:2021-12-10
通讯作者: Liu-Yi Zhang, Pei-Hua Peng, Wei-Min Yang
基金资助:
This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81560589, 30960450, 81173110 and 81560072), Yunnan Provincial Science and Technology Department (Nos. 202105AF150015, 202102AA310030, 2018FE001 (-026), 2017FE467 (-019), 2014BC012, and 2017IC041), and Yunnan Provincial Educational Department (Nos. 2018JS161).

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Ya-Juan Chen¹, Chen Chen¹, Meng-Yuan Li¹, Qing-Qing Li¹, Xiu-Juan Zhang¹, Rong Huang¹, Xing-Wei Zhu¹, Chun-Yun Bai¹, Liu-Yi Zhang¹, Pei-Hua Peng², Wei-Min Yang¹

1 School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 Western Chunrong Road, Yuhua Street, Chenggong New City, Kunming 650500, China;
2 Department of Anesthesiology, The First Affiliated Hospital of Kunming University, Kunming 650032, China

Received:2021-09-28 Online:2021-12-24 Published:2021-12-10
Contact: Liu-Yi Zhang, Pei-Hua Peng, Wei-Min Yang
Supported by:
This work was supported by Grants from the National Natural Science Foundation of China (Nos. 81560589, 30960450, 81173110 and 81560072), Yunnan Provincial Science and Technology Department (Nos. 202105AF150015, 202102AA310030, 2018FE001 (-026), 2017FE467 (-019), 2014BC012, and 2017IC041), and Yunnan Provincial Educational Department (Nos. 2018JS161).

摘要/Abstract

摘要： Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 μM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10-1000 μM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 μM). Pre-incubation with SCU (500 μM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 μM) was added. The brain slice staining test in rats' model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

关键词: Scutellarin, Basilar artery, Vascular endothelium, Ischemia reperfusion, PKG

Abstract: Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 μM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10-1000 μM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 μM). Pre-incubation with SCU (500 μM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 μM) was added. The brain slice staining test in rats' model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

Key words: Scutellarin, Basilar artery, Vascular endothelium, Ischemia reperfusion, PKG

Ya-Juan Chen, Chen Chen, Meng-Yuan Li, Qing-Qing Li, Xiu-Juan Zhang, Rong Huang, Xing-Wei Zhu, Chun-Yun Bai, Liu-Yi Zhang, Pei-Hua Peng, Wei-Min Yang. Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal[J]. 应用天然产物, 2021, 11(6): 659-670.

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Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

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