Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease

Diabetes Metab Syndr Obes. 2024 Apr 18:17:1795-1808. doi: 10.2147/DMSO.S449792. eCollection 2024.

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.

Keywords: db/db mice; diabetic kidney disease (DKD); mixture of astragalus; rhubarb; saffron; transcriptome sequencing.

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (No. 81960142), the Talent Innovation and Entrepreneurship Project of Lanzhou City, Gansu Province (No. 2021-RC-94), the Lanzhou City Chengguan District Science and Technology Bureau (No. 2021RCCX0027), the Cuiying Scientific and Technological Innovation Program of Lanzhou University Second Hospital (No. CY2017-QN19 and CY2021-QNB01), Scientific Research Projects of Colleges in Gansu Province (No. 2021B-041) and Gansu Provincial Department of Education project (2022B-050), the Technology Fund Program of Gansu Province (No. 21JR1RA157 and 23JRRA0991), and the Clinical Medical Research Center of Gansu Province (No. 21JR7RA436).