Molecular mechanism of Chuanxiong Rhizoma in treating coronary artery diseases
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摘要:
Abstract:
Objective: Most of the studies on the herb Chuanxiong Rhizoma (CR) have focused on the l-arginine-nitric oxide (NO) pathway, but the nitrate-nitrite-NO (NO3?-NO2?-NO) pathway was rarely investigated. Therefore, the aim of this study was to evaluate the effects and mechanisms of action of CR in coronary artery disease (CAD). Methods: The NO3?, NO2? and NO levels were examined in the NO3?-NO2?-NO pathway. High-performance ion chromatography was used to quantify NO3? and NO2? levels. Then, NO was quantified using a multifunctional enzyme marker with a fluorescent probe. The tension of aortic rings was measured using a multi myograph system. Results: High content of NO3? and low content of NO2? was found in CR, and which could potently convert NO3? to NO2? in the presence of endogenous reductase enzyme. Incubating human coronary artery endothelial cells (HCAECs) with CR-containing serum showed that CR significantly decreased the NO3? content and increased the levels of NO2? and NO in the cells under hypoxic conditions. In addition, CR significantly relaxed isolated aortic rings when the l-arginine -NO pathway was blocked. The optimal concentration of CR for relaxation was 200 mg/mL. Conclusion: CR supplements large amounts of NO in cells and vessels to achieve relaxation via the NO3?-NO2?-NO pathway, thereby making up for the deficiency caused by the lack of NO after the l-arginine-NO pathway is suppressed. This study also supports the potential use of a traditional Chinese herb for future drug development.
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This work was supported by the National Natural Science Foundation of China [grant No. 81774115, 2018]; National Natural Science Foundation of China [grant No. 81460721, 2015]; and Guangxi University of Traditional Chinese Medicine Key Master’s Research and Innovation Project of China [grant No. XYJ20080, 2020].