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

Xinyuan Ye; Ling Xiong; Qifeng Fu; Binyou Wang; Yiwei Wang; Kailian Zhang; Jie Yang; Fahsai Kantawong; Warunee Kumsaiyai; Jie Zhou; Cai Lan; Jianming Wu; Jing Zeng

doi:10.1016/j.jep.2022.115203

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

J Ethnopharmacol. 2022 Jun 28:292:115203. doi: 10.1016/j.jep.2022.115203. Epub 2022 Mar 15.

Authors

Xinyuan Ye¹, Ling Xiong², Qifeng Fu³, Binyou Wang⁴, Yiwei Wang⁵, Kailian Zhang⁶, Jie Yang⁷, Fahsai Kantawong⁸, Warunee Kumsaiyai⁹, Jie Zhou¹⁰, Cai Lan¹¹, Jianming Wu¹², Jing Zeng¹³

Affiliations

¹ School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
² School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
³ School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
⁴ School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
⁵ School of Pharmacy, Southwest Medical University, Luzhou, China; State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic address: [email protected].
⁶ School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
⁷ School of Pharmacy, Southwest Medical University, Luzhou, China; Faculty Associated Medical Sciences, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand. Electronic address: [email protected].
⁸ Faculty Associated Medical Sciences, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand. Electronic address: [email protected].
⁹ Faculty Associated Medical Sciences, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand. Electronic address: [email protected].
¹⁰ School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, Luzhou, China; Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou, China; Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
¹¹ School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, Luzhou, China; Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou, China; Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
¹² School of Pharmacy, Southwest Medical University, Luzhou, China; Education Ministry Key Laboratory of Medical Electrophysiology, Luzhou, China; Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou, China; Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Southwest Medical University, Luzhou, China. Electronic address: [email protected].
¹³ School of Pharmacy, Southwest Medical University, Luzhou, China. Electronic address: [email protected].

PMID: 35304277
DOI: 10.1016/j.jep.2022.115203

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 IC₅₀ 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.

Keywords: DPP-IV inhibitor; Diprotin A; Gynura divaricata (L.) DC.; Tripeptide; Type 2 diabetes mellitus.

MeSH terms

Asteraceae*
Diabetes Mellitus, Type 2* / drug therapy
Dipeptidyl-Peptidase IV Inhibitors* / chemistry
Dipeptidyl-Peptidase IV Inhibitors* / pharmacology
Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use
Molecular Docking Simulation

Substances

Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents