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<p>Stachydrine, the primary alkaloid component of <i>Leonurus japonicus</i> Houtt., Lamiaceae, has exhibited diverse bioactivities in the treatment of brain injuries, uterine diseases, cardiovascular diseases, fibrosis, inflammation, and cancers. Nevertheless, the significance of stachydrine in diabetic nephropathy remains unclear. In this research, our objective is to determine the functions and roles of stachydrine in rats with diabetic nephropathy and the underlying mechanisms of stachydrine in renal cells (NRK-52E) exposed to high glucose <i>in vitro</i>. For <i>in vivo</i> analysis, Sprague–Dawley rats were randomly assigned to the control, stachydrine, streptozotocin, streptozotocin + stachydrine, and streptozotocin + metformin (positive control) groups, with 10 rats in each group. Renal pathological lesions were evaluated using hematoxylin and eosin staining and periodic acid-Schiff staining. Immunofluorescence staining, western blotting, and TUNEL staining were also conducted on kidney samples. For <i>in vitro</i> analysis, NRK-52E cells were exposed to high glucose and stachydrine treatment. CCK-8 assays, flow cytometry, DCFH-DA assays, western blotting were carried out using NRK-52E cells. The results of this study revealed that stachydrine significantly alleviated renal function impairment and renal histopathological lesions in streptozotocin-induced diabetic rats. Specifically, stachydrine enhanced kidney autophagy by activating the AMPK/mTOR pathway, suppressed oxidative stress by activating the Nrf2/HO-1 pathway, and also restricted renal apoptosis in diabetic rats. Moreover, <i>in vitro</i> experiments demonstrated that stachydrine inhibited high glucose–induced oxidative stress and apoptosis and promoted autophagy by regulating the AMPK/mTOR and Nrf2/HO-1 pathways. In conclusion, this study demonstrated the protective effects of stachydrine on the kidneys of diabetic rats, which might exert by regulating autophagy, oxidative stress, and apoptosis through the AMPK/mTOR and Nrf2/HO-1 pathways.</p> Graphical Abstract <p></p>

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Stachydrine Protects Against Diabetic Nephropathy Through Modulating Autophagy, Oxidative Stress, and Apoptosis via the AMPK/mTOR and Nrf2/HO-1 Pathways

  • 期刊论文

  • 发表日期：

    2025年9月4日

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  • Fang Xie,
  • Chao Wang

摘要

Stachydrine, the primary alkaloid component of Leonurus japonicus Houtt., Lamiaceae, has exhibited diverse bioactivities in the treatment of brain injuries, uterine diseases, cardiovascular diseases, fibrosis, inflammation, and cancers. Nevertheless, the significance of stachydrine in diabetic nephropathy remains unclear. In this research, our objective is to determine the functions and roles of stachydrine in rats with diabetic nephropathy and the underlying mechanisms of stachydrine in renal cells (NRK-52E) exposed to high glucose in vitro. For in vivo analysis, Sprague–Dawley rats were randomly assigned to the control, stachydrine, streptozotocin, streptozotocin + stachydrine, and streptozotocin + metformin (positive control) groups, with 10 rats in each group. Renal pathological lesions were evaluated using hematoxylin and eosin staining and periodic acid-Schiff staining. Immunofluorescence staining, western blotting, and TUNEL staining were also conducted on kidney samples. For in vitro analysis, NRK-52E cells were exposed to high glucose and stachydrine treatment. CCK-8 assays, flow cytometry, DCFH-DA assays, western blotting were carried out using NRK-52E cells. The results of this study revealed that stachydrine significantly alleviated renal function impairment and renal histopathological lesions in streptozotocin-induced diabetic rats. Specifically, stachydrine enhanced kidney autophagy by activating the AMPK/mTOR pathway, suppressed oxidative stress by activating the Nrf2/HO-1 pathway, and also restricted renal apoptosis in diabetic rats. Moreover, in vitro experiments demonstrated that stachydrine inhibited high glucose–induced oxidative stress and apoptosis and promoted autophagy by regulating the AMPK/mTOR and Nrf2/HO-1 pathways. In conclusion, this study demonstrated the protective effects of stachydrine on the kidneys of diabetic rats, which might exert by regulating autophagy, oxidative stress, and apoptosis through the AMPK/mTOR and Nrf2/HO-1 pathways.

Graphical Abstract