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Updated: Mar 2, 2026
Author Spotlight: Investigating the Potential of Chinese Herbal Medicinal Active Dioscin in Treating IgA Nephropathy
Published on: October 13, 2023
Protective effects of dioscin against cisplatin-induced nephrotoxicity via the microRNA-34a/sirtuin 1 signalling
Yimeng Zhang1, Xufeng Tao1, Lianhong Yin1
1College of Pharmacy, Dalian Medical University, Dalian, China.
Background And Purpose:
Dioscin exhibits a range of pharmacological actions but little is known of its effects on cisplatin (CDDP)-induced nephrotoxicity. Here, we have assessed the effects and the possible mechanisms of dioscin against CDDP-induced nephrotoxicity.
Experimental Approach:
We used an in vivo model of CDDP-induced nephrotoxicity in rats and mice and, in vitro, cultures of NRK-52E and HK-2 cells. The dual luciferase reporter assay was used to demonstrate modulation, by dioscin, of the targeting of sirtuin 1 (Sirt1) by microRNA (miR)-34a. Molecular docking assays were used to analyse the effects of dioscin with Sirt1, Keap1 and NF-κB.
Key Results:
Dioscin attenuated cell damage in vitro and decreased renal injury in rats and mice, treated with CDDP. In terms of mechanisms, dioscin reversed CDDP-induced up-regulation of miR-34a and thus up-regulated Sirt1 levels. In addition, dioscin altered levels of haem oxygenase 1, glutathione-cysteine ligase subunits (GCLC, GCLM) and Keap1, along with increased nuclear translocation of Nrf2, thus decreasing oxidative stress. Also, dioscin affected levels of AP-1, COX-2, HMGB1, IκB-α, IL-1β, IL-6 and TNF-α and decreased the ratio of acetylated NF-κB and normal NF-κB, to suppress inflammation. From molecular docking assays, dioscin directly bound to Sirt1, Keap1 and NF-κBp65 by hydrogen bonding and/or hydrophobic interactions.
Conclusions And Implications:
Our results have linked CDDP-induced nephrotoxicity and the miR-34a/Sirt1 signalling pathway, which was modulated by dioscin. This natural product could be developed as a new candidate to alleviate CDDP-induced renal injury.
Insights
Dioscin protects against cisplatin-induced kidney damage by modulating the miR-34a/Sirt1 pathway, reducing oxidative stress and inflammation. This natural compound shows potential for alleviating renal injury.
Area of Science:
- Pharmacology
- Nephrology
- Molecular Biology
Background:
- Cisplatin (CDDP) is a widely used chemotherapy agent with significant nephrotoxicity.
- The protective effects of dioscin against CDDP-induced nephrotoxicity are largely unknown.
- Understanding dioscin's mechanisms against kidney injury is crucial for its therapeutic development.
Purpose of the Study:
- To investigate the protective effects of dioscin against cisplatin-induced nephrotoxicity.
- To elucidate the underlying molecular mechanisms of dioscin's action.
- To explore the role of the miR-34a/Sirt1 signaling pathway in dioscin's renoprotective effects.
Main Methods:
- In vivo studies using CDDP-treated rats and mice.
- In vitro experiments with NRK-52E and HK-2 kidney cell lines.
- Dual luciferase reporter assay to assess miR-34a and Sirt1 interaction.
- Molecular docking to analyze dioscin's binding to key proteins (Sirt1, Keap1, NF-κB).
Main Results:
- Dioscin significantly attenuated CDDP-induced renal cell damage and kidney injury.
- Dioscin reversed CDDP-induced upregulation of miR-34a, leading to increased Sirt1 levels.
- Dioscin reduced oxidative stress by modulating Nrf2 pathway components and suppressed inflammation by inhibiting NF-κB signaling.
- Molecular docking confirmed direct binding of dioscin to Sirt1, Keap1, and NF-κBp65.
Conclusions:
- Dioscin effectively protects against cisplatin-induced nephrotoxicity.
- The protective effects are mediated through modulation of the miR-34a/Sirt1 pathway, reduction of oxidative stress, and suppression of inflammation.
- Dioscin represents a promising natural product candidate for preventing or treating chemotherapy-induced kidney injury.
