Abstract

The main purpose of this study was to investigate the protective effects of total isoflavones from Radix Puerariae (PTIF) in diabetic rats. Diabetes was induced by a high-fat diet and intraperitoneal injection of low-dose streptozotocin (STZ; 40 mg/kg). At 26 weeks onwards, PTIF 421 mg/kg was administrated to the rats once daily consecutively for 10 weeks. Metabolic profiling changes were analyzed by Ultraperformance Liquid Chromatography-Quadrupole-Exactive Orbitrap-Mass Spectrometry (UPLC-Q-Exactive Orbitrap-MS). The principal component discriminant analysis (PCA-DA), partial least-squares discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used for multivariate analysis. Moreover, free amino acids in serum were determined by high-performance liquid chromatography with fluorescence detector (HPLC-FLD). Additionally, oxidative stress and inflammatory cytokines were evaluated. Eleven potential metabolite biomarkers, which are mainly related to the coagulation, lipid metabolism, and amino acid metabolism, have been identified. PCA-DA scores plots indicated that biochemical changes in diabetic rats were gradually restored to normal after administration of PTIF. Furthermore, the levels of BCAAs, glutamate, arginine, and tyrosine were significantly increased in diabetic rats. Treatment with PTIF could regulate the disturbed amino acid metabolism. Consequently, PTIF has great therapeutic potential in the treatment of DM by improving metabolism disorders and inhibiting oxidative damage.

Highlights

  • Diabetes mellitus (DM), a typical complex metabolic disease characterized by insulin deficiency or insulin resistance, can induce a series of complications such as nephropathy, cardiovascular diseases, and diabetic retinopathy

  • Considering the DM is associated with metabolic disorders, advanced oxidative stress, and chronic inflammation, we evaluated the therapeutic effects of Puerariae Radix on diabetic rats model induced by a high-fat diet and low-dose streptozotocin and explored the metabolomics profiles using Ultraperformance Liquid ChromatographyQuadrupole-Exactive Orbitrap-Mass Spectrometry and liquid chromatography with fluorescence detector

  • This study shows that the administration of PTIF may contribute to improving the lipid metabolism in diabetic organism

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Summary

Introduction

Diabetes mellitus (DM), a typical complex metabolic disease characterized by insulin deficiency or insulin resistance, can induce a series of complications such as nephropathy, cardiovascular diseases, and diabetic retinopathy. Puerariae Radix, the dried root of Pueraria lobata (Willd.) Ohwi, is known as Gegen and Kudzu. It is an important source of isoflavones, including puerarin, daidzin, genistin, daidzein, and genistein (Figure 1), which are considered to be the principal bioactive ingredients [5]. Gegen has been used widely in traditional Chinese classical prescriptions for diabetes treatment, such as Gegen Qinlian decoction, Huangqi Gengen decoction, and Yuquan Wan. Emerging evidence indicates that the extract of Puerariae Radix can improve antioxidant defense system by reducing the plasma level of coenzyme Q9 and MDA [6].

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