2. Academic Validation
  3. New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases

New horizons in the roles and associations of COX-2 and novel natural inhibitors in cardiovascular diseases

  • Mol Med. 2021 Sep 30;27(1):123. doi: 10.1186/s10020-021-00358-4.
Wujun Chen # 1,  Yingjie Zhong # 1,  Nuan Feng 2,  Zhu Guo 3,  Shuai Wang 4,  Dongming Xing 5 6
Affiliations

Affiliations

  • 1 Cancer Institute, Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China.
  • 2 Department of Nutrition, Qingdao Women and Children's Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 3 Cancer Institute, Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. guozhugz@126.com.
  • 4 School of Medical Imaging, Radiotherapy Department of Affiliated Hospital, Weifang Medical University, Weifang, 261053, Shandong, China. sdwftcmws@163.com.
  • 5 Cancer Institute, Department of Spine Surgery, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. xdm_tsinghua@163.com.
  • 6 School of Life Sciences, Tsinghua University, Beijing, 100084, China. xdm_tsinghua@163.com.
  • # Contributed equally.
PMID: 34592918 DOI: 10.1186/s10020-021-00358-4
Abstract

Age-related Cardiovascular Disease is the leading cause of death in elderly populations. Coxibs, including celecoxib, valdecoxib, etoricoxib, parecoxib, lumiracoxib, and rofecoxib, are selective cyclooxygenase-2 (COX-2) inhibitors used to treat osteoarthritis and rheumatoid arthritis. However, many coxibs have been discontinued due to adverse cardiovascular events. COX-2 contains cyclooxygenase (COX) and peroxidase (POX) sites. COX-2 inhibitors block COX activity without affecting POX activity. Recently, quercetin-like flavonoid compounds with OH groups in their B-rings have been found to serve as activators of COX-2 by binding the POX site. Galangin-like flavonol compounds serve as inhibitors of COX-2. Interestingly, nabumetone, flurbiprofen axetil, piketoprofen-amide, and nepafenac are ester prodrugs that inhibit COX-2. The combination of galangin-like flavonol compounds with these prodrug metabolites may lead to the development of novel COX-2 inhibitors. This review focuses on the most compelling evidence regarding the role and mechanism of COX-2 in cardiovascular diseases and demonstrates that quercetin-like compounds exert potential cardioprotective effects by serving as cofactors of COX-2.

Keywords

COX-2; Cardiovascular; Coxibs; Galangin; Quercetin.

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