Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway
Gaofei Ren,1 Pengfei Jiao,2 Yushan Yan,1 Xiaojun Ma,1 Guijun Qin1 1Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’...
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| Format: | Article |
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Dove Medical Press
2023-04-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
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| Online Access: | https://www.dovepress.com/baicalin-exerts-a-protective-effect-in-diabetic-nephropathy-by-repress-peer-reviewed-fulltext-article-DMSO |
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| author | Ren G Jiao P Yan Y Ma X Qin G |
| author_facet | Ren G Jiao P Yan Y Ma X Qin G |
| author_sort | Ren G |
| collection | DOAJ |
| description | Gaofei Ren,1 Pengfei Jiao,2 Yushan Yan,1 Xiaojun Ma,1 Guijun Qin1 1Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Xiaojun Ma; Guijun Qin, Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-0371-66295052, Email fccmaxj1@zzu.edu.cn; hyqingj@zzu.edu.cnBackground: Inflammation and oxidative stress contribute to the development of diabetic nephropathy (DN). Baicalin (BA) shows renal protection against DN through its anti-inflammatory and anti-oxidant properties. However, the molecular mechanism by which BA exerts the therapeutic effects on DN remains to be investigated.Methods: The db/db mice and high glucose (HG)-induced HK-2 cells were used as the in vivo and in vitro model of DN, respectively. The effects of BA were assessed by detecting the related blood and urine biochemical parameters, kidney histopathology, inflammatory cytokine production, oxidative stress indicators, and apoptosis. Cell viability and apoptosis were detected by CCK-8 assay and TUNEL assay, respectively. Related protein levels were measured by an immunoblotting method.Results: In db/db model mice, BA reduced serum glucose concentration, decreased blood lipid levels, ameliorated kidney functions, and decreased histopathological changes in kidney tissues. BA also alleviated oxidative stress and inflammation in db/db mice. In addition, BA blocked the activation of sphingosine kinases type 1/sphingosine 1-phosphate (SphK1/S1P)/NF-κB pathway in db/db mice. In HK-2 cells, BA hindered HG-induced apoptosis, oxidative stress and inflammation, while overexpression of SphK1 or S1P could reverse these effects. BA alleviated HG-induced apoptosis, oxidative stress and inflammation in HK-2 cells through the S1P/NF-κB pathway. Furthermore, BA blocked the NF-κB signaling by diminishing p65 nuclear translocation via the SphK1/S1P pathway.Conclusion: Our study strongly suggests that BA protects against DN via ameliorating inflammation, oxidative stress and apoptosis through the SphK1/S1P/NF-κB pathway. This study provides a novel insight into the therapeutic effects of BA in DN.Keywords: diabetic nephropathy, baicalin, SphK1/S1P/NF-κB pathway, inflammation, oxidative stress |
| first_indexed | 2024-04-09T15:35:29Z |
| format | Article |
| id | doaj.art-6bdb1eec85134ebe836dc6ea39844b32 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-09T15:35:29Z |
| publishDate | 2023-04-01 |
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| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-6bdb1eec85134ebe836dc6ea39844b322023-04-27T19:02:46ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072023-04-01Volume 161193120583304Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling PathwayRen GJiao PYan YMa XQin GGaofei Ren,1 Pengfei Jiao,2 Yushan Yan,1 Xiaojun Ma,1 Guijun Qin1 1Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Xiaojun Ma; Guijun Qin, Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-0371-66295052, Email fccmaxj1@zzu.edu.cn; hyqingj@zzu.edu.cnBackground: Inflammation and oxidative stress contribute to the development of diabetic nephropathy (DN). Baicalin (BA) shows renal protection against DN through its anti-inflammatory and anti-oxidant properties. However, the molecular mechanism by which BA exerts the therapeutic effects on DN remains to be investigated.Methods: The db/db mice and high glucose (HG)-induced HK-2 cells were used as the in vivo and in vitro model of DN, respectively. The effects of BA were assessed by detecting the related blood and urine biochemical parameters, kidney histopathology, inflammatory cytokine production, oxidative stress indicators, and apoptosis. Cell viability and apoptosis were detected by CCK-8 assay and TUNEL assay, respectively. Related protein levels were measured by an immunoblotting method.Results: In db/db model mice, BA reduced serum glucose concentration, decreased blood lipid levels, ameliorated kidney functions, and decreased histopathological changes in kidney tissues. BA also alleviated oxidative stress and inflammation in db/db mice. In addition, BA blocked the activation of sphingosine kinases type 1/sphingosine 1-phosphate (SphK1/S1P)/NF-κB pathway in db/db mice. In HK-2 cells, BA hindered HG-induced apoptosis, oxidative stress and inflammation, while overexpression of SphK1 or S1P could reverse these effects. BA alleviated HG-induced apoptosis, oxidative stress and inflammation in HK-2 cells through the S1P/NF-κB pathway. Furthermore, BA blocked the NF-κB signaling by diminishing p65 nuclear translocation via the SphK1/S1P pathway.Conclusion: Our study strongly suggests that BA protects against DN via ameliorating inflammation, oxidative stress and apoptosis through the SphK1/S1P/NF-κB pathway. This study provides a novel insight into the therapeutic effects of BA in DN.Keywords: diabetic nephropathy, baicalin, SphK1/S1P/NF-κB pathway, inflammation, oxidative stresshttps://www.dovepress.com/baicalin-exerts-a-protective-effect-in-diabetic-nephropathy-by-repress-peer-reviewed-fulltext-article-DMSOdiabetic nephropathybaicalinsphk1/s1p/nf-κb pathwayinflammationoxidative stress |
| spellingShingle | Ren G Jiao P Yan Y Ma X Qin G Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway Diabetes, Metabolic Syndrome and Obesity diabetic nephropathy baicalin sphk1/s1p/nf-κb pathway inflammation oxidative stress |
| title | Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway |
| title_full | Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway |
| title_fullStr | Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway |
| title_full_unstemmed | Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway |
| title_short | Baicalin Exerts a Protective Effect in Diabetic Nephropathy by Repressing Inflammation and Oxidative Stress Through the SphK1/S1P/NF-κB Signaling Pathway |
| title_sort | baicalin exerts a protective effect in diabetic nephropathy by repressing inflammation and oxidative stress through the sphk1 s1p nf kappa b signaling pathway |
| topic | diabetic nephropathy baicalin sphk1/s1p/nf-κb pathway inflammation oxidative stress |
| url | https://www.dovepress.com/baicalin-exerts-a-protective-effect-in-diabetic-nephropathy-by-repress-peer-reviewed-fulltext-article-DMSO |
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