Chemical characterization and DPP-IV inhibitory activity evaluation of tripeptides from Gynura divaricata (L.) DC. (28th June 2022)

• Record Type: Journal Article
• Authors: Ye, Xinyuan; Xiong, Ling; Fu, Qifeng; Wang, Binyou; Wang, Yiwei; Zhang, Kailian; Yang, Jie; Kantawong, Fahsai; Kumsaiyai, Warunee; Zhou, Jie; Lan, Cai; Wu, Jianming; Zeng, Jing
• Is Part Of: Journal of ethnopharmacology. Volume 292(2022)
• Publication Date: 2022-06-28
• Subjects: Type 2 diabetes mellitus -- Gynura divaricata (L.) DC. -- Tripeptide -- DPP-IV inhibitor -- Diprotin A; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115203
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Gynura divaricata (L.) DC. (GD), a herbal medicine, has been used for the prevention and treatment of hyperglycemia in China. However, hypoglycemic ingredients within GD have not yet been well studied. Aim of the study: The aim of this study was to explore undiscovered compounds with dipeptidyl peptidase IV (DPP-IV) inhibitory activity within GD. Materials and methods: A four-step strategy was developed to explore undiscovered DPP-IV inhibitors within GD. First, the components were preliminarily characterized using UHPLC-HRMS combined with a library search. Second, preliminarily characterized compounds were searched for potential bioactivity. Third, a mixture of these preliminarily characterized compounds was isolated and thoroughly characterized based on fragmentation patterns associated with molecular networking. Fourth, the activities of these compounds were verified using DPP-IV inhibitory assay and molecular docking. Results: Diprotin A, a tripeptide inhibitor against DPP-IV, was identified. Thereafter, a mixture of twenty-five diprotin A analogs was isolated and characterized, which exhibited IC 50 of 0.40 mg/mL for DPP-IV. Molecular docking results also confirmed the interactions between the tripeptide analogs and DPP-IV mainly via H-bonds and hydrophobic interactions. Conclusions: This is the first report of DPP-IV inhibitors within GD. These findings demonstrate that the extract of GD might be beneficial for the treatment of type 2 diabetes mellitus, and is expected to promote further development and utilization of GD in herbal medicine. Graphical abstract: Image 1 Highlights: A four-step strategy was developed for chemical characterization and activity evaluation. The DPP-IV inhibitors within Gynura divaricata (L.) DC. (GD) were characterized and evaluated for the first time. The findings are validated that GD is a potential herbal medicine for blood sugar regulation.