Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity
ObjectiveTo investigate the protective effect of ginsenoside Rb1 on renal tubular epithelial cell injury in diabetic kidney disease and its mechanism.MethodsPrimary human renal cortical proximal tubular epithelial cells （HK-2） were cultured in vitro. HK-2 cells were divided into the control group， c...
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Editorial Department of Journal of Clinical Nephrology
2025-07-01
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| Series: | Linchuang shenzangbing zazhi |
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| author | Wang Meng-jing Luo Yi Liu Shu-fen Yuan Shuang Huang Hao |
| author_facet | Wang Meng-jing Luo Yi Liu Shu-fen Yuan Shuang Huang Hao |
| author_sort | Wang Meng-jing |
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| description | ObjectiveTo investigate the protective effect of ginsenoside Rb1 on renal tubular epithelial cell injury in diabetic kidney disease and its mechanism.MethodsPrimary human renal cortical proximal tubular epithelial cells （HK-2） were cultured in vitro. HK-2 cells were divided into the control group， control ＋ ginsenoside Rb1 （10 μmol/L） group， high glucose （30 mmol/L） group， high glucose （30 mmol/L） ＋ ginsenoside Rb1 （10 μmol/L） group， and high glucose （30 mmol/L） ＋ epalrestat （100 μmol/L） group. db/m and db/db mice at 16 weeks of age were randomly divided into the db/m group， db/m ＋ ginsenoside Rb1 （40 mg/kg oral gavage） group， db/db group， and db/db ＋ ginsenoside Rb1 （40 mg/kg oral gavage） group. Western blotting was used to detect expression levels of the apoptosis-related proteins ［B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved caspase-3］， oxidative stress-related proteins ［caspase 9， cytochrome complex （Cyt C）， and NADPH oxidase 4 （NOX4）］， and aldose reductase （AR）. Flow cytometry was used to observe the apoptotic rate of HK-2 cells. Reactive oxygen species （ROS） and Mitochondrial Superoxide Indicator （MitoSOX） fluorescence staining were used to detect the oxidative stress level of HK-2 cells. The binding ability of ginsenoside Rb1 to AR was detected by molecular docking. The changes in renal tubular mesangium were observed by PAS staining.ResultsIn comparison to the control group， protein level of Bcl-2 （0.37±0.12 <italic>vs</italic> 1.16±0.10） was significantly lower， while those of Bax （2.18±0.08 <italic>vs</italic> 1.16±0.03）， cleaved caspase 3 （2.17±0.09 <italic>vs</italic> 1.14±0.02）， caspase 9 （2.16±0.08 <italic>vs</italic> 1.20±0.03）， Cyt C （1.98±0.09 <italic>vs</italic> 1.13±0.06） and NOX4 （2.15±0.11 <italic>vs</italic> 1.20±0.07） were significantly higher in the high glucose group （<italic>P</italic><0.001）. In comparison to the high glucose group， protein level of Bcl-2 （0.62±0.30 <italic>vs</italic> 0.37±0.12） was significantly higher， while those of Bax （0.73±0.08 <italic>vs</italic> 2.18±0.08）， cleaved caspase 3 （0.68±0.10 <italic>vs</italic> 2.17±0.09）， caspase 9 （1.62±0.12 <italic>vs</italic> 2.16±0.08）， Cyt C （1.59±0.10 <italic>vs</italic> 1.98±0.09） and NOX4 （1.52±0.08 <italic>vs</italic> 2.15±0.11） were significantly lower in the high glucose ＋ ginsenoside Rb1 group （<italic>P</italic><0.01）. In comparison to the control group， ROS （43.85±3.25 <italic>vs</italic> 25.06±2.68） and MitoSOX levels （60.08±2.32 <italic>vs</italic> 22.50±0.68） were significantly higher in the high glucose group （<italic>P</italic><0.001）. In comparison to the high glucose group， ROS （30.15±3.52 <italic>vs</italic> 43.85±3.25） and MitoSOX levels （32.06±1.89 <italic>vs</italic> 60.08±2.32） were significantly lower in the high glucose ＋ ginsenoside Rb1 group （<italic>P</italic><0.01）. Molecular docking showed that ginsenoside Rb1 could stably bind to AR protein. Compared with the high glucose group， MitoSOX level was both significantly reduced in the high glucose ＋ ginsenoside Rb1 group （21.08±2.48 <italic>vs</italic> 44.85±2.08） and high glucose ＋ epalrestat group （23.62±2.28 <italic>vs</italic> 44.85±2.08）， showing a similar outcome （<italic>P</italic><0.01）. Compared with the db/db group， mice in the db/db ＋ ginsenoside Rb1 group had significantly lower body weight ［（41.49±2.54） g <italic>vs</italic> （46.80±5.16） g］， blood sugar ［（26.98±3.53） mmol/L <italic>vs</italic> （30.22±3.49） mmol/L］ and urine albumin-creatinine ratio ［（8.43±3.31） mg/g <italic>vs</italic> （11.40±2.20） mg/g］ （<italic>P</italic><0.001）. Compared with the db/m group， mice in the db/db group showed obvious glycogen deposition in renal tubules， mesangial matrix expansion， and higher mesangial area fraction （0.67±0.10 <italic>vs</italic> 0.24±0.05） （<italic>P</italic><0.001）. Compared with the db/db group， mice in the db/db ＋ ginsenoside Rb1 group presented significantly alleviated glycogen deposition and mesangial matrix expansion in the renal tubules， with a significantly lower mesangial area fraction （0.36±0.04 <italic>vs</italic> 0.67±0.10） （<italic>P</italic><0.01）.ConclusionGinsenoside Rb1 can bind to AR and inhibit its activity to reduce renal tubular epithelial cell injury in high glucose environment. |
| format | Article |
| id | doaj-art-06d6b45cedbe4f67a2ea206e52faa7b0 |
| institution | Matheson Library |
| issn | 1671-2390 |
| language | zho |
| publishDate | 2025-07-01 |
| publisher | Editorial Department of Journal of Clinical Nephrology |
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| spelling | doaj-art-06d6b45cedbe4f67a2ea206e52faa7b02025-07-26T19:00:07ZzhoEditorial Department of Journal of Clinical NephrologyLinchuang shenzangbing zazhi1671-23902025-07-0125594603117476006Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activityWang Meng-jingLuo YiLiu Shu-fenYuan ShuangHuang HaoObjectiveTo investigate the protective effect of ginsenoside Rb1 on renal tubular epithelial cell injury in diabetic kidney disease and its mechanism.MethodsPrimary human renal cortical proximal tubular epithelial cells （HK-2） were cultured in vitro. HK-2 cells were divided into the control group， control ＋ ginsenoside Rb1 （10 μmol/L） group， high glucose （30 mmol/L） group， high glucose （30 mmol/L） ＋ ginsenoside Rb1 （10 μmol/L） group， and high glucose （30 mmol/L） ＋ epalrestat （100 μmol/L） group. db/m and db/db mice at 16 weeks of age were randomly divided into the db/m group， db/m ＋ ginsenoside Rb1 （40 mg/kg oral gavage） group， db/db group， and db/db ＋ ginsenoside Rb1 （40 mg/kg oral gavage） group. Western blotting was used to detect expression levels of the apoptosis-related proteins ［B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved caspase-3］， oxidative stress-related proteins ［caspase 9， cytochrome complex （Cyt C）， and NADPH oxidase 4 （NOX4）］， and aldose reductase （AR）. Flow cytometry was used to observe the apoptotic rate of HK-2 cells. Reactive oxygen species （ROS） and Mitochondrial Superoxide Indicator （MitoSOX） fluorescence staining were used to detect the oxidative stress level of HK-2 cells. The binding ability of ginsenoside Rb1 to AR was detected by molecular docking. The changes in renal tubular mesangium were observed by PAS staining.ResultsIn comparison to the control group， protein level of Bcl-2 （0.37±0.12 <italic>vs</italic> 1.16±0.10） was significantly lower， while those of Bax （2.18±0.08 <italic>vs</italic> 1.16±0.03）， cleaved caspase 3 （2.17±0.09 <italic>vs</italic> 1.14±0.02）， caspase 9 （2.16±0.08 <italic>vs</italic> 1.20±0.03）， Cyt C （1.98±0.09 <italic>vs</italic> 1.13±0.06） and NOX4 （2.15±0.11 <italic>vs</italic> 1.20±0.07） were significantly higher in the high glucose group （<italic>P</italic><0.001）. In comparison to the high glucose group， protein level of Bcl-2 （0.62±0.30 <italic>vs</italic> 0.37±0.12） was significantly higher， while those of Bax （0.73±0.08 <italic>vs</italic> 2.18±0.08）， cleaved caspase 3 （0.68±0.10 <italic>vs</italic> 2.17±0.09）， caspase 9 （1.62±0.12 <italic>vs</italic> 2.16±0.08）， Cyt C （1.59±0.10 <italic>vs</italic> 1.98±0.09） and NOX4 （1.52±0.08 <italic>vs</italic> 2.15±0.11） were significantly lower in the high glucose ＋ ginsenoside Rb1 group （<italic>P</italic><0.01）. In comparison to the control group， ROS （43.85±3.25 <italic>vs</italic> 25.06±2.68） and MitoSOX levels （60.08±2.32 <italic>vs</italic> 22.50±0.68） were significantly higher in the high glucose group （<italic>P</italic><0.001）. In comparison to the high glucose group， ROS （30.15±3.52 <italic>vs</italic> 43.85±3.25） and MitoSOX levels （32.06±1.89 <italic>vs</italic> 60.08±2.32） were significantly lower in the high glucose ＋ ginsenoside Rb1 group （<italic>P</italic><0.01）. Molecular docking showed that ginsenoside Rb1 could stably bind to AR protein. Compared with the high glucose group， MitoSOX level was both significantly reduced in the high glucose ＋ ginsenoside Rb1 group （21.08±2.48 <italic>vs</italic> 44.85±2.08） and high glucose ＋ epalrestat group （23.62±2.28 <italic>vs</italic> 44.85±2.08）， showing a similar outcome （<italic>P</italic><0.01）. Compared with the db/db group， mice in the db/db ＋ ginsenoside Rb1 group had significantly lower body weight ［（41.49±2.54） g <italic>vs</italic> （46.80±5.16） g］， blood sugar ［（26.98±3.53） mmol/L <italic>vs</italic> （30.22±3.49） mmol/L］ and urine albumin-creatinine ratio ［（8.43±3.31） mg/g <italic>vs</italic> （11.40±2.20） mg/g］ （<italic>P</italic><0.001）. Compared with the db/m group， mice in the db/db group showed obvious glycogen deposition in renal tubules， mesangial matrix expansion， and higher mesangial area fraction （0.67±0.10 <italic>vs</italic> 0.24±0.05） （<italic>P</italic><0.001）. Compared with the db/db group， mice in the db/db ＋ ginsenoside Rb1 group presented significantly alleviated glycogen deposition and mesangial matrix expansion in the renal tubules， with a significantly lower mesangial area fraction （0.36±0.04 <italic>vs</italic> 0.67±0.10） （<italic>P</italic><0.01）.ConclusionGinsenoside Rb1 can bind to AR and inhibit its activity to reduce renal tubular epithelial cell injury in high glucose environment.http://www.lcszb.com/thesisDetails#10.3969/j.issn.1671-2390.2025.07.009Ginsenoside Rb1Diabetic kidney diseaseAldose reductaseRenal tubular epithelial cell |
| spellingShingle | Wang Meng-jing Luo Yi Liu Shu-fen Yuan Shuang Huang Hao Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity Linchuang shenzangbing zazhi Ginsenoside Rb1 Diabetic kidney disease Aldose reductase Renal tubular epithelial cell |
| title | Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| title_full | Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| title_fullStr | Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| title_full_unstemmed | Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| title_short | Ginsenoside Rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| title_sort | ginsenoside rb1 alleviates renal tubular epithelial cell injury in diabetic kidney disease by inhibiting the aldose reductase activity |
| topic | Ginsenoside Rb1 Diabetic kidney disease Aldose reductase Renal tubular epithelial cell |
| url | http://www.lcszb.com/thesisDetails#10.3969/j.issn.1671-2390.2025.07.009 |
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