Anti-diabetic potential of Pueraria lobata root extract through promoting insulin signaling by PTP1B inhibition

Ran Sun; Xinxian Deng; Dongdong Zhang; Fangzhou Xie; Di Wang; Juntao Wang; Mojdeh S Tavallaie; Faqin Jiang; Lei Fu

doi:10.1016/j.bioorg.2019.02.046

Anti-diabetic potential of Pueraria lobata root extract through promoting insulin signaling by PTP1B inhibition

Bioorg Chem. 2019 Jun:87:12-15. doi: 10.1016/j.bioorg.2019.02.046. Epub 2019 Feb 22.

Authors

Ran Sun¹, Xinxian Deng¹, Dongdong Zhang¹, Fangzhou Xie¹, Di Wang¹, Juntao Wang¹, Mojdeh S Tavallaie¹, Faqin Jiang², Lei Fu³

Affiliations

¹ Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University (SJTU), 800 Dongchuan Road, Shanghai 200240, China.
² Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University (SJTU), 800 Dongchuan Road, Shanghai 200240, China. Electronic address: [email protected].
³ Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, Shanghai Jiao Tong University (SJTU), 800 Dongchuan Road, Shanghai 200240, China. Electronic address: [email protected].

PMID: 30852232
DOI: 10.1016/j.bioorg.2019.02.046

Abstract

Type 2 diabetes mellitus is a fast-growing epidemic affecting people globally. We initiated the project by searching the possible target of the Pueraria lobata root extract (P. lobata). We conducted the IC₅₀ assays of P. lobata on the four diabetes-related proteins: PTP1B, TCPTP, SHP-2 and DPP-4. Results indicated that P. lobata exhibited high PTP1B inhibitory activity with IC₅₀ of 0.043 mg/ml. Treated insulin-resistant HepG2 cells with 0.0115 mg/ml of P. lobata increased the glucose uptake by two times compared with the negative control. Further, we performed OGTT test on the diabetic C57BL/6 male mice. 20% decreased blood glucose (AUC) was obtained with a dose of 1 g/kg P. lobata compared with the negative control. Herein, we were able to demonstrate the antidiabetic effects of P. lobata might be related to the inhibition of PTP1B and therefore, bettering the insulin signaling pathway.

Keywords: Anti-diabetic activities; PTP1B; Pueraria lobata; T2DM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Proliferation / drug effects
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / metabolism
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Hep G2 Cells
Humans
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / isolation & purification
Hypoglycemic Agents / pharmacology*
Insulin / metabolism*
Male
Mice
Mice, Inbred C57BL
Molecular Docking Simulation
Molecular Structure
Plant Extracts / chemistry
Plant Extracts / isolation & purification
Plant Extracts / pharmacology*
Plant Roots / chemistry
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Pueraria / chemistry*
Signal Transduction / drug effects
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents, Phytogenic
Hypoglycemic Agents
Insulin
Plant Extracts
PTPN1 protein, human
Protein Tyrosine Phosphatase, Non-Receptor Type 1