Advances in nitric oxide regulators for the treatment of ischemic stroke

Jianbing Wu; Jian Jia; Duorui Ji; Weijie Jiao; Zhangjian Huang; Yihua Zhang

doi:10.1016/j.ejmech.2023.115912

Advances in nitric oxide regulators for the treatment of ischemic stroke

Eur J Med Chem. 2023 Dec 15:262:115912. doi: 10.1016/j.ejmech.2023.115912. Epub 2023 Oct 30.

Authors

Jianbing Wu¹, Jian Jia², Duorui Ji¹, Weijie Jiao¹, Zhangjian Huang³, Yihua Zhang⁴

Affiliations

¹ State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China.
² State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China; Novel Technology Center of Pharmaceutical Chemistry, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
³ State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: zhangjianhuang@cpu.edu.cn.
⁴ State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: zyhtgd@163.com.

PMID: 37931330
DOI: 10.1016/j.ejmech.2023.115912

Abstract

Ischemic stroke (IS) is a life-threatening disease worldwide. Nitric oxide (NO) derived from l-arginine catalyzed by NO synthase (NOS) is closely associated with IS. Three isomers of NOS (nNOS, eNOS and iNOS) produce different concentrations of NO, resulting in quite unlike effects during IS. Of them, n/iNOSs generate high levels of NO, detrimental to brain by causing nerve cell apoptosis and/or necrosis, whereas eNOS releases small amounts of NO, beneficial to the brain via increasing cerebral blood flow and improving nerve function. As a result, a large variety of NO regulators (NO donors or n/iNOS inhibitors) have been developed for fighting IS. Regrettably, up to now, no review systematically introduces the progresses in this area. This article first outlines dynamic variation rule of NOS/NO in IS, subsequently highlights advances in NO regulators against IS, and finally presents perspectives based on concentration-, site- and timing-effects of NO production to promote this field forward.

Keywords: Dynamic variation rule of NOS/NO; Ischemic stroke; NO regulators; NO synthase (NOS); Nitric oxide (NO).

Publication types

Review

MeSH terms

Arginine
Enzyme Inhibitors / pharmacology
Humans
Ischemic Stroke*
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Nitric Oxide*

Substances

Nitric Oxide
Enzyme Inhibitors
Nitric Oxide Synthase
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type II
Arginine