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Background <p>The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor to chronic kidney disease (CKD), are urgently&#xa0;needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, the renoprotective effects of Notoginsenoside R2 (NR2), an active component of PNG, on DN have not been investigated. This study aimed to assess the therapeutic potential of NR2 in DN and explore its underlying mechanisms.</p> Methods <p><i>In&#xa0;vivo</i>&#xa0;models were&#xa0;developed&#xa0;using&#xa0;db/db&#xa0;mice,&#xa0;while&#xa0;in vitro models&#xa0;utilized&#xa0;HK-2&#xa0;cells&#xa0;exposed&#xa0;to high glucose and palmitic acid (HGPA). Online databases and Cytoscape software were&#xa0;employed&#xa0;to predict the potential&#xa0;targets&#xa0;of NR2. The expression of associated proteins was measured using immunohistochemistry and western blot. Lipid accumulation, oxidative stress&#xa0;levels, mitochondrial&#xa0;function and cell apoptosis were also&#xa0;assessed.&#xa0;Small&#xa0;interfering RNA was used in in vitro&#xa0;experiments&#xa0;to examine the effect of&#xa0;c-Src.</p> Results <p>NR2 ameliorated albuminuria, renal function and renal pathology in db/db&#xa0;mice. The activation of c-Src was suppressed in db/db mice and in HK-2 cells exposed to HGPA. NR2 inhibited JNK/STAT1 phosphorylation and CD36 overexpression. NR2 also ameliorated lipid accumulation, oxidative stress, mitochondrial dysfunction and cell apoptosis in vivo and in vitro. By&#xa0;inhibiting&#xa0;c-Src,&#xa0;HK-2 cells exposed to HGPA experienced less&#xa0;lipid deposition and mitochondrial&#xa0;damage,&#xa0;indicating the renoprotective effects of NR2 were correlated with the inhibition of c-Src.</p> Conclusion <p>NR2 ameliorated mitochondrial dysfunction and delayed the progression of DN partly through suppression of c-Src. The protective effects of NR2 might be related to a reduction in lipid accumulation.</p> Graphical Abstract <p></p>

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Protective effects of Notoginsenoside R2 on reducing lipid accumulation and mitochondrial dysfunction in diabetic nephropathy through regulation of c-Src

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月15日

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  • Xieyi Guo,
  • Liu Yang,
  • Xiaoning An,
  • Maofang Hu,
  • Yilan Shen,
  • Niansong Wang,
  • Youhua Xu,
  • Dingkun Gui

摘要

Background

The treatment options to delay the progression of diabetic nephropathy (DN), a key contributor to chronic kidney disease (CKD), are urgently needed. Previous studies reported that traditional Chinese medicine Panax notoginseng (PNG) exerted beneficial effects on DN. However, the renoprotective effects of Notoginsenoside R2 (NR2), an active component of PNG, on DN have not been investigated. This study aimed to assess the therapeutic potential of NR2 in DN and explore its underlying mechanisms.

Methods

In vivo models were developed using db/db mice, while in vitro models utilized HK-2 cells exposed to high glucose and palmitic acid (HGPA). Online databases and Cytoscape software were employed to predict the potential targets of NR2. The expression of associated proteins was measured using immunohistochemistry and western blot. Lipid accumulation, oxidative stress levels, mitochondrial function and cell apoptosis were also assessed. Small interfering RNA was used in in vitro experiments to examine the effect of c-Src.

Results

NR2 ameliorated albuminuria, renal function and renal pathology in db/db mice. The activation of c-Src was suppressed in db/db mice and in HK-2 cells exposed to HGPA. NR2 inhibited JNK/STAT1 phosphorylation and CD36 overexpression. NR2 also ameliorated lipid accumulation, oxidative stress, mitochondrial dysfunction and cell apoptosis in vivo and in vitro. By inhibiting c-Src, HK-2 cells exposed to HGPA experienced less lipid deposition and mitochondrial damage, indicating the renoprotective effects of NR2 were correlated with the inhibition of c-Src.

Conclusion

NR2 ameliorated mitochondrial dysfunction and delayed the progression of DN partly through suppression of c-Src. The protective effects of NR2 might be related to a reduction in lipid accumulation.

Graphical Abstract