2. Academic Validation
  3. The activation of histone deacetylases 4 prevented endothelial dysfunction: A crucial mechanism of HuangqiGuizhiWuwu Decoction in improving microcirculation dysfunction in diabetes

The activation of histone deacetylases 4 prevented endothelial dysfunction: A crucial mechanism of HuangqiGuizhiWuwu Decoction in improving microcirculation dysfunction in diabetes

  • J Ethnopharmacol. 2023 Feb 8;116240. doi: 10.1016/j.jep.2023.116240.
Meijiang Chen 1,  Hong Cheng 2,  Xinyi Chen 3,  Jiangyong Gu 4,  Weiwei Su 5,  Gaize Cai 6,  Yue Yan 7,  Chen Wang 8,  Xiaoye Xia 9,  Kaitong Zhang 10,  Meng Zhang 11,  Haiqiang Jiang 12,  Yongjun Chen 13,  Lin Yao 14
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: 20201110588@stu.gzucm.edu.cn.
  • 2 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: cheng029615@163.com.
  • 3 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: muguetvalley@163.com.
  • 4 School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: gujy@gzucm.edu.cn.
  • 5 Guangdong Engineering and Technology Research Center for Quality and Efficacy Re-evaluation of Post-marketed TCM, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, PR China. Electronic address: lsssww@126.com.
  • 6 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: 13690031400@163.com.
  • 7 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: yanyueyyyyyy@163.com.
  • 8 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: limited_xchen@163.com.
  • 9 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: xxy9992022@163.com.
  • 10 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: 2020052067@stu.gzucm.edu.cn.
  • 11 Research Institute of Acupuncture and Moxibustion, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China. Electronic address: mzhang30@sdutcm.edu.cn.
  • 12 Research Institute of Acupuncture and Moxibustion, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China. Electronic address: jhq12723@163.com.
  • 13 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China; Research Institute of Acupuncture and Moxibustion, Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, PR China. Electronic address: chyj417@126.com.
  • 14 School of Pharmaceutical Sciences, South China Research Center for Acupuncture and Moxibustion, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address: yaolin526@126.com.
PMID: 36764560 DOI: 10.1016/j.jep.2023.116240
Abstract

Ethnopharmacological relevance: The regulation of epigenetic factors is considered a crucial target for solving complex chronic diseases such as cardio-cerebrovascular diseases. HuangqiGuizhiWuwu Decoction (HGWWD), a classic Chinese prescription, is mainly used to treat various vascular diseases. Although our previous studies reported that HGWWD could effectively prevent vascular dysfunction in diabetic rodent models, the precise mechanism is still elusive.

Aim of the study: In this study, we investigated the epigenetic mechanisms of modulating the damage of vascular endothelial cells in diabetes by HGWWD.

Methods: We first analyzed common active components of HGWWD by using HPLC-Q-TOF-MS/MS analysis, and predicted the isoforms of histone deacetylase (HDAC) that can potentially combine the above active components by systems pharmacology. Next, we screened the involvement of specific HDAC isoforms in the protective effect of HGWWD on vascular injury by using pharmacological blockade combined with the evaluation of vascular function in vivo and in vitro.

Results: Firstly, HDAC1, HDAC2, HDAC3, HDAC4, HDAC6, HDAC7, SIRT2, and SIRT3 have been implicated with the possibility of binding to the thirty-one common active components in HGWWD. Furthermore, the protective effect of HGWWD is reversed by both TSA (HDAC Inhibitor) and MC1568 (class II HDAC Inhibitor) on vascular impairment accompanied by reduced aortic HDAC activity in STZ mice. Finally, inhibition of HDAC4 blocked the protective effect of HGWWD on microvascular and endothelial dysfunction in diabetic mice.

Conclusions: These results prove the key role of HDAC4 in diabetes-induced microvascular dysfunction and underlying epigenetic mechanisms for the protective effect of HGWWD in diabetes.

Keywords

Diabetes; Endothelial dysfunction; HDAC4; HuangqiGuizhiWuwu decoction; Microvascular injury.

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