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Natural product cycloastragenol: a promising anti-diabetes candidate with therapeutic effects on its related complications in rats
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  • Qi Zhang,
  • Sui-qi Cheng,
  • Jia-wei Sun,
  • Zhi-yin Sun,
  • Wang Peng,
  • Guo-tao Kuang,
  • Xiao-xuan Su,
  • Xiao-na Wang,
  • Yong Rao,
  • Tian-miao Ou
Qi Zhang
Guangzhou University of Chinese Medicine
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Sui-qi Cheng
Sun Yat-Sen University
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Jia-wei Sun
Sun Yat-Sen University
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Zhi-yin Sun
Sun Yat-Sen University
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Wang Peng
Sun Yat-Sen University
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Guo-tao Kuang
Sun Yat-Sen University
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Xiao-xuan Su
Sun Yat-Sen University
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Xiao-na Wang
Sun Yat-Sen University
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Yong Rao
Sun Yat-Sen University
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Tian-miao Ou
Sun Yat-Sen University
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Abstract

BACKGROUND AND PURPOSE Type II Diabetes mellitus (T2DM) is a worrying chronic metabolic disorder accompanied by multiple serious complications, makes threaten public health. In the present study, we evaluated the therapeutic effects against T2DM of the cycloastragenol (CAG), a key metabolite of astragaloside IV (AST) isolated from traditional Chinese plant Astragalus membranaceus and revealed its molecular mechanism. EXPERIMENTAL APPROACH The plasma glucose-decreasing effects of AST and CAG were monitored in KunMing mice by performing an OGTT test. Furthermore, the effect of CAG on the metabolism of Zuker diabetic fat (ZDF) rats was demonstrated after treatment for 5 weeks, as well as on diabetes-relevant clinical symptoms and glucose absorbance. The underlying molecular mechanism of the therapeutic effects of CAG was explored in both wild-type and sodium/glucose co-transporter 2 (SGLT2)-overexpressed HEK293 cells. KEY RESULTS CAG showed stronger effects in lowering plasma glucose and enhancing glucose tolerance than AST in KM mice and ZDF rats. In the ZDF rats, the potential antidiabetic properties of CAG were associated with amelioration in hyperglycemia, dyslipidemia, myocardial and kidney fibrosis. Interestingly, glucose reuptake was inhibited in the kidneys of mice treated with CAG, while urine glucose and sodium levels were elevated. The underlying mechanism might be that CAG reduced the expression of SGLT2 in the kidney and inhibited glucose transport as well. CONCLUSIONS AND IMPLICATIONS CAG can ameliorate the T2DM-related metabolic syndromes of ZDF rats by acting on the SGLT2, which provides a certain references for the application of CAG in T2DM therapy.