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The Combined Administration of Disulfiram and Baicalin Alleviates Membranous Nephropathy by Inhibiting Podocyte
Chengli Lou1, Yijing Zhou2, Bo Feng1
1Department of Nephropathy, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, Zhejiang, China.
Background:
Membranous nephropathy (MN) is an autoimmune kidney disease, and its pathogenesis is related to inflammation and podocyte injury. Both disulfiram and baicalin can relieve the symptoms of MN through anti-inflammatory effects. However, it is still unclear whether disulfiram and baicalin can enhance the therapeutic effect of MN by combination therapy.
Methods:
We screened the optimal drug concentration of disulfiram and baicalin for incubation of AB8/13 cells by CCK-8 assay. Angiotensin II was used to stimulate AB8/13 cells to construct a MN cell model. Subsequently, cell proliferation assays, network pharmacology analysis, ELISA assay, and pyroptosis detection were employed to investigate the effects of disulfiram combined with baicalin in MN.
Results:
Firstly, 250 nM disulfiram and 5 μmol/L baicalin were selected as the optimal dose for the treatment of MN. Cell proliferation assay showed that the combined administration of disulfiram and baicalin could reduce Angiotensin II-induced podocyte injury. Subsequently, a total of 129 genes were identified as potential therapeutic targets of the combination therapy involving disulfiram and baicalin for MN. These targets mainly focused on regulating inflammatory-related functions and pathways. Disulfiram combined with baicalin inhibited the inflammation of MN by suppressing the levels of TNF-α, IL-8 and C-reactive protein and promoting the levels of TGF-β and IL-10. Disulfiram combined with baicalin significantly attenuated Angiotensin II-induced podocyte pyroptosis, as indicated by reduction of Caspase-1 and GSDMD-N, lactate dehydrogenase release and the percentage of podocytes stained with propidium iodide.
Conclusion:
Compared with monotherapy using either disulfiram or baicalin alone for MN, the combination has a protective role in podocyte injury by inhibiting inflammation and pyroptosis. This discovery provides a new perspective for clarifying the pharmacological effects of disulfiram and baicalin to podocyte injury in MN.
Insights
Combination therapy with disulfiram and baicalin offers a protective effect against membranous nephropathy (MN) by reducing inflammation and pyroptosis in kidney podocytes. This approach shows enhanced therapeutic potential compared to individual treatments for MN.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Membranous nephropathy (MN) is an autoimmune kidney disease driven by inflammation and podocyte injury.
- Disulfiram and baicalin exhibit anti-inflammatory properties beneficial for MN.
- The combined therapeutic effect of disulfiram and baicalin in MN remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of combined disulfiram and baicalin therapy in a cellular model of membranous nephropathy (MN).
- To explore the underlying mechanisms, including inflammation and pyroptosis, affected by this combination therapy.
Main Methods:
- Optimal drug concentrations of disulfiram and baicalin were determined using CCK-8 assays.
- A membranous nephropathy (MN) cell model was established by stimulating AB8/13 cells with Angiotensin II.
- Cell proliferation, network pharmacology, ELISA, and pyroptosis assays were performed to assess treatment effects.
Main Results:
- Combined disulfiram and baicalin treatment reduced Angiotensin II-induced podocyte injury and inflammation.
- Network pharmacology identified 129 potential therapeutic targets related to inflammatory pathways.
- The combination therapy suppressed key inflammatory markers (TNF-α, IL-8, C-reactive protein) and promoted anti-inflammatory cytokines (TGF-β, IL-10), while attenuating pyroptosis indicators (Caspase-1, GSDMD-N).
Conclusions:
- Combination therapy with disulfiram and baicalin demonstrates a significant protective role in podocyte injury in MN.
- This combination effectively inhibits inflammation and pyroptosis, offering advantages over monotherapy.
- The findings provide a novel perspective on the pharmacological mechanisms of disulfiram and baicalin in mitigating podocyte damage in MN.
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