Tetrahydropalmatine triggers angiogenesis via regulation of arginine biosynthesis. (January 2021)

• Record Type: Journal Article
• Authors: Cui, Herong; Yang, Xuexin; Wang, Zhidong; Li, Guoping; Li, Lei; Huo, Su; Zhang, Beibei; He, Rui; Chen, Kedian; Xu, Bing; Wang, Penglong; Lei, Haimin
• Is Part Of: Pharmacological research. Volume 163(2021)
• Publication Date: 2021-01
• Subjects: Tetrahydropalmatine (PubChem CID: 72301) -- Gastrodin (PubChem CID: 115067); Tetrahydropalmatine -- Angiogenesis -- Metabolomics -- Arginine biosynthesis; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.105242
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Highlights: Tetrahydropalmatine (THP) was identified as a proangiogenic trigger. THP induces angiogenesis in a dose-dependent manner. THP promotes proliferation, tube formation, and migration of HUVECs. Arginine biosynthesis is the main metabolic pathways regulated by THP. THP affects citrulline to arginine flux, arginine biosynthesis and angiogenesis. Abstract: Over a short span of two decades, the central role of angiogenesis in the treatment of wound healing, diverse cancers, nerve defect, vascular injury and several ophthalmic diseases has become evident. Tetrahydropalmatine, as the index component of Corydalis yanhusuo W. T. Wang, is inseparable from protecting cardiovascular system, yet its role in angiogenesis has been poorly characterized. We have demonstrated the binding potential of THP and VEGFR2 using molecular docking based on the clinical experience of traditional Chinese medicine in the pretest study. Here, we identified tetrahydropalmatine (THP) as one proangiogenic trigger via regulation of arginine biosynthesis by pharmacological assays and DESI-MSI/GC–MS based metabolomics. First, the proangiogenic effects of THP were evaluated by quail chorioallantoic membrane test in vivo and multiple models of endothelial cells in vitro . According to virtual screening, the main mechanisms of THP (2/5 of the top terms with smaller p -value) were metabolic pathways. Hence, metabolomics was applied for the main mechanisms of THP and results showed the considerable metabolite difference in arginine biosynthesis ( p < 0.05) altered by THP. Finally, correlated indicators were deteced using targeted metabolomics and pharmacological assays for validation, and results suggested the efficacy of THP on citrulline to arginine flux, arginine biosynthesis, and endothelial VEGFR2 expression sequentially, leading to the promotion of angiogenesis. Overall, this manuscript identified THP as the proangiogenic trigger with the potential to develop as pharmacological agents for unmet clinical needs.