Effects of (L.) and Its Combination with Irbesartan in the Treatment of Diabetic Nephropathy Via the Gut-kidney Axis

Overview

Journal Front Pharmacol

Date 2024 Nov 12

PMID 39529886

Authors

Hongmei Yu

Haitao Tang

Rengui Saxu

Yuhui Song

Xu Cui

Jingjing Xu

Nan Li

Siyuan Cui

Haitao Ge

Wei Tang

Harvest F Gu

Affiliations

Soon will be listed here.

Abstract

Background: Clinical observations have recently shown that (L.) in the form of Huangkui capsule (HKC) and in combination with irbesartan (EB) is an effective therapy for diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). The present study aims to explore the mechanisms underlying the therapeutic efficacies of HKC and its combination with EB in DN via the gut-kidney axis.

Methods: HKC, EB, and their combination or vehicle were administered in db/db mice, which is an animal model for the study of T2D and DN. Comparative analyses of the gut microbiota, serum metabolites, and kidney transcriptomics before and after drug administration were performed.

Results: After treatment with HKC, EB, and their combination for 4 weeks, the urinary albumin-to-creatinine ratios decreased significantly in the db/db mice with DN. In terms of the gut microbiota, the abundances of Faecalitalea, Blautia, and Streptococcus increased but those of Bacteroidetes, Firmicutes, Enterobacteriaceae, and Desulfovibrio decreased. Parallelly, serum metabolites, mainly including quercetin 3'-glucuronide and L-dopa, were elevated while cortisol and cytochalasin B were reduced. Furthermore, the , , , and genes in the kidneys were downregulated. These altered elements were associated with proteinuria/albuminuria reduction. However, EB had no effects on the changes in blood pressure and specific differentially expressed genes in the kidneys.

Conclusion: The present study provides experimental evidence that HKC regulates the gut microbiota, circulating metabolites, and renal gene activities, which are useful for better understanding of the action mechanisms of in the treatment of DN through the gut-kidney axis.

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