Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine.
10.1016/S1875-5364(22)60151-1
- Author:
You-Xu WANG
1
;
Ning CAO
1
;
Hui-Da GUAN
1
;
Xue-Mei CHENG
1
;
Chang-Hong WANG
2
Author Information
1. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai 201203, China.
2. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, Shanghai 201203, China. Electronic address: wchcxm@shutcm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Harmaline;
Harmine;
Heme peroxidases;
Horseradish peroxidase;
Lactoperoxidase;
Myeloperoxidase;
Oxidative dehydrogenation
- MeSH:
Animals;
Harmaline/metabolism*;
Harmine/metabolism*;
Heme;
Hydrogen Peroxide;
Rats;
Tandem Mass Spectrometry
- From:
Chinese Journal of Natural Medicines (English Ed.)
2022;20(3):194-201
- CountryChina
- Language:English
-
Abstract:
Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.
