Abstract

Hyperglycemia is a strong risk factor for chronic complications of diabetes. Hyperglycemic conditions foster not only the production of reactive oxygen species (ROS), but also the consumption of antioxidants, leading to oxidative stress and promoting the occurrence and progression of complications. During our continuous search for antioxidant constituents from the pericarp of Toona sinensis (A. Juss.) Roem, we isolated two previously unreported apotirucallane-type triterpenoids, toonasinensin A (1) and toonasinensin B (2), together with five known apotirucallane-type triterpenoids (3–7) and two known cycloartane-type triterpenoids (8–9) from the pericarp. Compounds 8–9 were obtained from T. sinensis for the first time. Their structures were characterized based on interpretation of spectroscopic data (1D, 2D NMR, high-resolution electrospray ionization mass spectra, HR-ESI-MS) and comparison to previous reports. Compounds (2, 4, 6, 7, and 9) were able to inhibit proliferation against rat glomerular mesangial cells (GMCs) cultured under high-glucose conditions within a concentration of 80 μM. Compounds (2, 6, and 7) were tested for antioxidant activity attributable to superoxide dismutase (SOD), malondialdehyde (MDA), and ROS in vitro, and the results showed that compounds (2, 6, and 7) could significantly increase the levels of SOD and reduce the levels of MDA and ROS. The current studies showed that apotirucallane-type triterpenoids (2, 6, and 7) might have the antioxidant effects against diabetic nephropathy.

Highlights

  • Diabetic nephropathy (DN) is one of the most common complications of diabetes, and the occurrence and development of oxidative stress play an important role [1,2]

  • Excessive oxidative stress could lead to inflammation, fibrosis, the cell apoptosis, and cell damage and death, which are considered as an important pathological change in DN [3]

  • Juss.) Roem is traditional Chinese medicine belonging to the genus Toona and the family Meliaceae, which is widely distributed across Asia [4,5]

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Summary

Introduction

Diabetic nephropathy (DN) is one of the most common complications of diabetes, and the occurrence and development of oxidative stress play an important role [1,2]. T. sinensis is rich in triterpenoids, to possess variety of pharmacological activities, including antioxidant [10], anti-inflammatory phenols,aalkaloids, saponins, sterols, coumarin, and anthraquinone [6,7,8,9]. No study hasisyet reported the extraction separation of chemical the pericarp we of T. sinensis, which often discarded as waste.and. We described the isolation and structures of two previously unreported triterpenoids, toonasinensin A (1) and toonasinensin B (2), and those of five known apotirucallane-type apotirucallane-type triterpenoids, toonasinensin A (1) and toonasinensin B (2), and those of five triterpenoids (3–7) and two known cycloartane-type triterpenoids (8–9) (Figure 1). Oxidative stress activities of compounds 1–9 were evaluated in rat glomerular mesangial cells (GMCs). The reducing oxidative stress activities of compounds 1–9 were evaluated in rat cultured under high-glucose conditions.

Discussion
Compounds
Procedures
Extraction and Isolation
Cytotoxicity Assay
Cell Proliferation Assay
Statistical Analysis
Conclusions
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