Mitochondria targeting fluorescent probe for MAO-A and the application in the development of drug candidate for neuroinflammation

Monoamine oxidase A (MAO-A), as a vital drug target for various central nervous system diseases, locates in mitochondria and is mainly responsible for the oxidative inactivation of neurotransmitter amines. In the present work, a Mito-targeting fluorescent probe (HCCP) was developed to selectively and sensitively detect MAO-A activity, and successfully applied for the real-time monitoring endogenous MAO-A in living cells and tissues. Additionally, a high-throughput screening platform was established using HCCP and the inhibitory effects of 210 kinds of Herbal medicines toward MAO-A were evaluated. Evocarpine as a novel inhibitor for MAO-A was discovered from Evodia rutaecarpa, which possessed the preferred anti-neuroinflammation activity by suppressing the iNOS expression and NO production in LPS-induced BV2 cells bioactivation. In summary, HCCP was a novel Mito-targeting tool for the real-time imaging of MAO-A, provided an efficient method for real-time exploring of physiological functions of MAO-A and developing potential inhibitors of MAO-A. (c) 2022 Elsevier B.V. All rights reserved.

Automated summary

In this study, a novel Mito-targeting tool HCCP was developed for real-time imaging and detection of MAO-A activity. A high-throughput screening platform was established using HCCP to evaluate the inhibitory effects of various herbal medicines on MAO-A, leading to the discovery of a novel MAO-A inhibitor Evocarpine. This study provides an efficient method for exploring the physiological functions of MAO-A and developing potential inhibitors.