Different Astragalus medicinal pairs improve diabetic nephropathy in mice by regulating lipid peroxidation through PTGS2

doi:10.12122/j.issn.1673-4254.2026.03.13

Abstract

Abstract:

Objective To explore the regulatory effects of 3 Astragalus herb pairs (Astragalus-Salvia miltiorrhiza, Astragalus-Rehmannia glutinosa, and Astragalus-Dioscorea opposita) in QidanDihuang Granule on PTGS2-mediated lipid peroxidation in mice with diabetic kidney disease (DKD). Methods Network pharmacology was used to screen active components and targets of Astragalus membranaceus, Salvia miltiorrhiza, Rehmannia glutinosa, and Dioscorea opposita in Qidan Dihuang Granule to construct herb pair-active component-target networks, followed by intersection analysis with DKD-related targets for PPI network construction and enrichment analysis. Molecular docking was used to verify the binding of the key active components to PTGS2. In 25 C57BL/6J mouse models of streptozotocin-induced DKD, the therapeutic effects of treatments with saline, irbesartan, and the 3 Astragalus herb pairs (n=5) for 8 weeks were tested, with 5 normal mice serving as the control group. Results Network pharmacology showed extensive intersections between the active components of each herb pair and DKD-related targets, with PTGS2 as the key target. The major active components exhibited good binding affinity to PTGS2. The DKD mouse models in Astragalus-Salvia miltiorrhiza and Astragalus-Rehmannia glutinosa groups, particularly those in the former group, showed significant improvements in body weight, fasting blood glucose, serum creatinine, urea nitrogen, and 24-h urinary albumin. The Astragalus-Dioscorea opposita pair only slightly improved blood glucose and creatinine without improving urea nitrogen or urinary albumin in the mouse models. The Astragalus-Salvia miltiorrhiza pair, but not the other two pairs, markedly reduced the elevation of PTGS2 expression, significantly enhanced SOD activity, reduced MDA content, and upregulated GPX4 expression in the mouse models, and the therapeutic effect was only moderate in Astragalus-Rehmannia glutinosa group and the poorest in Astragalus-Dioscorea opposita group. Conclusion The 3 Astragalus herb pairs from Qidan Dihuang Granule can improve DKD in mice by reducing PTGS2-mediated lipid peroxidation, and the Astragalus-Salvia miltiorrhiza pair shows the strongest efficacy.

Key words: Qidan Dihuang Granules, herb pair, diabetic kidney disease, lipid peroxidation, PTGS2

Xuejun CHEN, Yuan JING, Huiyu LIANG, Jingying ZHONG, Zedong CHEN, Yuzhi PENG, Jiaojiao DAI, Ya XIAO. Different Astragalus medicinal pairs improve diabetic nephropathy in mice by regulating lipid peroxidation through PTGS2[J]. Journal of Southern Medical University, 2026, 46(3): 592-603.

Figures/Tables 7

Fig.1 Identification of the effective components and targets of each Astragalus prescription for treatment of diabetic kidney disease (DKD). A-C: Bioactive components of each Astragalus herb pair and their targets. D: Disease-related targets of DKD screened from multiple databases. E-G: Intersection gene targets between each Astragalus herb pair and DKD.

Fig.2 Identification of the core targets of different Astragalus prescriptions for treatment of DKD. A, C, E: Protein-protein interaction (PPI) networks of shared genes between DKD and the herb pairs Astragalus-Salvia miltiorrhiza, Astragalus-Rehmannia, and Astragalus-Dioscorea, respectively. B, D, F: Core therapeutic targets of each herb pair against DKD.

Fig.3 Analysis of potential signaling pathways for treatment of DKD. A, C, E: Bubble plots of KEGG pathway enrichment analysis for shared genes between DKD and the herb pairs Astragalus-Salvia miltiorrhiza, Astragalus-Rehmannia, and Astragalus-Dioscorea, respectively. B, D, F: Gene Ontology (GO) analysis of shared genes between each herb pair and DKD, categorized into biological process (BP), molecular function (MF), and cellular component (CC).

Fig.4 Molecular docking analysis of bioactive compounds with the key core target PTGS2. A: PTGS2 and Daidzein. B: PTGS2 and formononetin. C: PTGS2 and kaempferol. D: PTGS2 and quercetin.

Fig.5 Therapeutic effects of the Astragalus combinations on kidney damage in DKD mice.A: Body weight in Control group, Model group, Irbesartan group, Astragalus and Danshen group (HQDS), Astragalus and Dioscorea opposita group (HQSY), and Astragalus and Rehmannia glutinosa group (HQDH) (n=5). B: Fasting blood glucose levels in each group (n=5). C: Serum creatinine levels in each group (n=5). D: Urea nitrogen levels in each group (n=5). E: 24-hour urinary albumin content in each group (n=5). F: Results of HE, periodic acid-Schiff (PAS), and Masson staining of mouse kidney tissue (Original magnification: ×400). G: Quantifications of PAS trichrome staining (n=3). H: Quantitative analysis of Masson staining results (n=3). Data are presented as Mean±SE. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.6 Expression and localization of PTGS2 in renal tissues of DKD mice. A: Immunohistochemical staining showing localization and expression level of PTGS2 protein in the renal tissues of each group (×400). B: Quantitative analysis of PTGS2 immunohistochemical staining intensity. C: Western blotting of PTGS2. D: Quantitative analysis of PTGS2 protein expression levels. Data are presented as Mean±SE. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Fig.7 Differential regulatory effects of the 3 Astragali herb pairs on lipid peroxidation in DKD mice. A: Malondialdehyde (MDA) levels in each group. B: Reactive oxygen species (ROS) levels in each group. C: Superoxide dismutase (SOD) levels in each group. D: Western blotting results of GPX4. E: Quantitative analysis of GPX4 protein expression levels. Data are presented as Mean±SE. *P<0.05.

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