Naodesheng decoction regulating vascular function via G-protein-coupled receptors: network analysis and experimental investigations

Shuhan Chen; Ziran Niu; Yanjia Shen; Wendan Lu; Jiaying Zhao; Huilin Yang; Minmin Guo; Li Zhang; Ruifang Zheng; Guanhua Du; Li Li

doi:10.3389/fphar.2024.1355169

Naodesheng decoction regulating vascular function via G-protein-coupled receptors: network analysis and experimental investigations

Front Pharmacol. 2024 Mar 12:15:1355169. doi: 10.3389/fphar.2024.1355169. eCollection 2024.

Authors

Shuhan Chen¹, Ziran Niu^{1

2}, Yanjia Shen¹, Wendan Lu¹, Jiaying Zhao¹, Huilin Yang¹, Minmin Guo¹, Li Zhang¹, Ruifang Zheng³, Guanhua Du¹, Li Li¹

Affiliations

¹ Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
³ Xinjiang Key Laboratory of Uygur Medicine, Xinjiang Institute of Materia Medica, Urumqi, Xinjiang, China.

Abstract

Introduction: Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including Panax notoginseng (Burk.) F. H. Chen, Ligusticum chuanxiong Hort., Carthamus tinctorius L., Pueraria lobata (Willd.) Ohwi, and Crataegus pinnatifida Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear. Methods: A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, β2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored. Results: The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in vitro in a dose-dependent manner. Several metabolites of NDS, including C. tinctorius, C. pinnatifida, and P. notoginseng, were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS. Discussion: The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.

Keywords: G-protein-coupled receptor; Naodesheng decoction; material basis; molecular docking; network analysis; vascular function.

Grants and funding

The authors declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-016 and 2016-I2M-3-007), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2023-RW350-01), the Major Scientific and Technological Special Project for “Significant New Drug Creation” (2013ZX09508104, 2013ZX09402203, and 2018ZX09711001-003-005), and the China Scholarship Council (201808110107).