Abstract

Catalpa pod has been used in traditional medicine for the treatment of diabetes mellitus in South America. Studies on the constituents of Catalpa species have shown that it is rich in iridoids. In the present study, three previously undescribed compounds (2–4), including two secoiridoid derivatives along with twelve known compounds, were isolated from the fruits of Catalpa bignonioides Walt. In addition, fully assigned 13C-NMR of 5,6-dihydroxy-7,4’-dimethoxyflavone-6-O-sophoroside (1) is reported for the first time in the present study. The structures of compounds were determined on the basis of extensive spectroscopic methods, including UV, IR, 1D, and 2D NMR, mass spectroscopy, and CD spectroscopic data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Among the tested compounds, compounds 2, 3, and 9 exhibited significant inhibitory activity against α-glucosidase enzyme assay. Meanwhile, the effect of compounds 2, 3, and 9 on glucose-stimulated insulin secretion (GSIS) was measured using pancreatic β-cells. Compounds 2, 3, and 9 exhibited non-cytotoxicity-stimulated insulin secretion in INS-1 cells. The expression levels of proteins associated with β-cell function and insulin secretion such as phosphorylation of total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, activated pancreatic duodenal homeobox-1 (PDX-1), and peroxisome proliferator-activated receptor-γ (PPAR-γ) were increased in INS-1 cells after treatment with compounds 2, 3, and 9. The findings of the present study could provide a scientific warrant for their application as a potential antidiabetic agent.

Highlights

  • Diabetes mellitus (DM) is a metabolic disease characterized by glucose intolerance and changes in lipid and protein metabolism [1]

  • Using various chromatographic resin and isolation techniques, one new flavone glycoside (2) and two new iridoids (3 and 4) along with twelve known compounds were isolated from the MeOH extract of the fruits of C. bignonioides

  • Treatment with compounds 2, 3, and 9 increased the expression of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt. These results suggested that compounds 2, 3, and 9 upregulate the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and pancreatic duodenal homeobox-1 (PDX-1), and upregulate the phosphorylation of IRS-2, PI3K, and Akt in INS-1 cells

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Summary

Introduction

Diabetes mellitus (DM) is a metabolic disease characterized by glucose intolerance and changes in lipid and protein metabolism [1]. DM can be divided into insulin-dependent diabetes mellitus (type 1) and non-insulin-dependent diabetes mellitus (type 2). Type 2 diabetes is a metabolic disorder resulting from the body’s inability to produce, and properly utilize insulin, which causes hyperglycemia [2]. Many oral hypoglycemic agents for clinical use are available for the treatment of DM, but these synthetic agents produce severe side effects such as hypoglycemia, weight gain, gastrointestinal disturbances, and liver toxicity [3]. (Bignoniaceae), commonly known as a bean tree, is a traditional folk medicine in South America for the treatment of gastric diseases, helmintic infections, oncological diseases, bronchial diseases, carbuncles, scabs, and abscesses [5] Catalpa bignonioides Walt. (Bignoniaceae), commonly known as a bean tree, is a traditional folk medicine in South America for the treatment of gastric diseases, helmintic infections, oncological diseases, bronchial diseases, carbuncles, scabs, and abscesses [5]

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