Abstract

Evidence indicates that the metabolic inflammation induced by gut microbiota dysbiosis contributes to diabetic kidney disease. Prebiotic supplementations to prevent gut microbiota dysbiosis, inhibit inflammatory responses, and protect the renal function in DKD. Qing-Re-Xiao-Zheng formula (QRXZF) is a Traditional Chinese Medicine (TCM) formula that has been used for DKD treatment in China. Recently, there are growing studies show that regulation of gut microbiota is a potential therapeutic strategy for DKD as it is able to reduce metabolic inflammation associated with DKD. However, it is unknown whether QRXZF is effective for DKD by regulating of gut microbiota. In this study, we investigated the reno-protective effect of QRXZF by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney. High-fat diet (HFD) and streptozotocin injection-induced DKD mice model was established to assess the QRXZF effect in vivo. Mice treated with QRXZF for 8 weeks had significantly lower levels of urinary albumin, serum cholesterol and triglycerides. The renal injuries observed through histological analysis were attenuated as well. Also, mice in the QRXZF group had higher levels of Zonula occludens protein-1 (ZO-1) expression, lower levels of serum fluorescein-isothiocyanate (FITC)-dextran and less-damaged colonic mucosa as compared to the DKD group, implying the benefit role for the gut barrier integrity. QRXZF treatment also reversed gut dysbiosis and reduced levels of gut-derived LPS. Notably, the expression of toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), which are important inflammation pathways in DKD, were suppressed in the QRXZF groups. In conclusion, our results indicated that the reno-protective effects of QRXZF was probably associated with modulating gut microbiota and inhibiting inflammatory responses in the kidney.

Highlights

  • Seven-week-old male C57BL/6J mice were purchased fromJiangsu-Jicui Yaokang Lab Animal Ltd

  • We investigated the reno-protective effect of Qing-Re-Xiao-Zheng formula (QRXZF) by exploring its potential mechanism between gut microbiota and downstream inflammatory pathways mediated by gut-derived lipopolysaccharide (LPS) in the kidney

  • Qing-Re-Xiao-Zheng formula (QRXZF) which was formulated based on the “ZhengJia” theory in Traditional Chinese Medicine (TCM) has been commonly used for Diabetic kidney disease (DKD) treatment [20]

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Summary

INTRODUCTION

Qing-Re-Xiao-Zheng formula (QRXZF) which was formulated based on the “ZhengJia” theory in TCM has been commonly used for DKD treatment [20]. It comprises of Astragali radix IV (Huang Qi), Radix angelicae sinensis (Dang Gui), Concha Ostreae (Mu Li), Rheum officinale Baill (Da Huang), and four other herbs. Since gut microbiota and inflammatory responses might lead to the progression of DKD [13, 14], our study aims to investigate the anti-inflammatory and reno-protective effects of QRXZF in DKD mice by observing alterations in gut microbiota and levels of gut-derived LPS and identifying the relationship between gut microbiota and DKD. Serum was diluted in phosphatebuffered saline (PBS) (1:1) and analyzed for FITC-dextran concentration by a fluorescence spectrophotometer (485 nm excitation, 535 nm emission)

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