2. Academic Validation
  3. Wogonin inhibits oxidative stress and vascular calcification via modulation of heme oxygenase-1

Wogonin inhibits oxidative stress and vascular calcification via modulation of heme oxygenase-1

  • Eur J Pharmacol. 2023 Sep 20;176070. doi: 10.1016/j.ejphar.2023.176070.
Lihe Lu 1,  Yining Li 2,  Qian Dong 3,  Jiansong Fang 4,  An Chen 2,  Zirong Lan 2,  Yuanzhi Ye 2,  Jianyun Yan 5,  Qingchun Liang 6
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China.
  • 2 Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, China.
  • 3 Department of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, China.
  • 4 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 5 Department of Cardiology, Laboratory of Heart Center, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, China. Electronic address: yanjy790@smu.edu.cn.
  • 6 Department of Anesthesiology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China. Electronic address: qingchun@i.smu.edu.cn.
PMID: 37739306 DOI: 10.1016/j.ejphar.2023.176070
Abstract

Vascular calcification (VC) is highly prevalent and increases the morbidity and mortality of cardiovascular diseases. However, the underlying mechanism remains unclear and there is no effective treatment so far. Interestingly, using systems pharmacology approach, we have predicted that Wogonin (Wog) exhibited potential activity against VC. Then we validated the effect of Wog on VC using human and rat vascular smooth muscle cells (VSMCs), rat arterial rings and vitamin D3-overloaded mouse models. Our results showed that Wog dose-dependently inhibited calcification of VSMCs and rat arterial rings. Consistently, alizarin red staining and calcium content assay confirmed that Wog inhibited aortic calcification in vitamin D3-overloaded mice. Moreover, by constructing the protein regulating network of Wog in suppressing VC, we found heme oxygenase-1 (HMOX-1) was regulated by Wog. Additionally, pathway enrichment analysis revealed that inhibition of Reactive Oxygen Species (ROS) pathway participated in the inhibitory role of Wog in VC and HMOX-1 was also involved in this process. Notably, our study revealed that Wog treatment promoted HMOX-1 expression, and reduced ROS levels in VSMCs. Interestingly, both inhibition of HMOX-1 by ZnPP9 and knockdown of HMOX-1 by siRNA independently eliminated the inhibitory effect of Wog on VC. Finally, administration of Wog suppressed aortic calcification in vitamin D3-overloaded mice and this effect was counteracted by ZnPP9,suggesting the crucial role of HMOX-1 in the inhibitory effect of Wog on VC. Collectively, this study combines systems pharmacology-based strategy and experiments to identify the therapeutic potential of Wog for VC via upregulating HMOX-1 and reducing oxidative stress.

Keywords

Heme oxygenase-1; Oxidative stress; Reactive oxygen species; Systems pharmacology; Vascular calcification; Wogonin.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z