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Abstract
Purpose
To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD).
Methods
Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis.
Results
Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes.
Conclusion
A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.
Abbreviations
Alas2, 5′-aminolevulinate synthase 2; BPs, biological processes; BUN, blood urea nitrogen; CCs, cell components; Ciita, class II major histocompatibility complex transactivator; CKD, chronic kidney disease; Creb5, cAMP responsive element binding protein 5; DEGs, differentially expressed genes; DKD, diabetic kidney disease; DM, diabetes mellitus; ESRD, end-stage renal disease; GO, Gene Ontology; Gpr68, G protein-coupled receptor 68; H2-DMa, histocompatibility 2, class II, locus DMa; H2-Eb1, histocompatibility 2, class II antigen E beta; Hba-a1, hemoglobin alpha, adult chain 1; Hba-a2, hemoglobin alpha, adult chain 2; Ifi47, interferon gamma-inducible protein 47; KEGG, Kyoto Encyclopedia of Genes and Genomes; MFs, molecular functions; MHC, major histocompatibility complex; PPI, protein-protein interaction; qRT-PCR, quantitative real-time polymerase chain reaction; SCr, serum creatinine; Spi1, Spi-1 proto-oncogene; TCM, traditional Chinese medicine; TNF, tumor necrosis factor; UAER, urinary albumin excretion rate.
Data Sharing Statement
All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.
Ethics Approval and Informed Consent
This study passed the review of the Ethics Committee of the Lanzhou University Second Hospital (Number: D2019-198). All experiments involving animals were performed after Lanzhou University Second Hospital Institutional Ethical Committee’s approval, and under the strict adherence to the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.
Author Contributions
All authors made significant contributions to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.
Disclosure
The authors declare that they have no competing interests in this work.