Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis
Abstract Background Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were...
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-023-00842-5 |
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| author | Rong Zheng Weijie Zhang Jufang Song Yifei Zhong Rong Zhu |
| author_facet | Rong Zheng Weijie Zhang Jufang Song Yifei Zhong Rong Zhu |
| author_sort | Rong Zheng |
| collection | DOAJ |
| description | Abstract Background Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were used to evaluate the diagnostic value of CRD. Methods Quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence analysis, and immunohistochemical staining were used to assess changes in mRNA and protein expression. Oxidative stress was evaluated by detecting the production of reactive oxygen species (ROS) and the activity of antioxidant enzymes. Cell apoptosis was detected by the TUNEL and flow cytometric methods. The interaction of miR-193b-5p and myeloid leukemia 1 (MCL-1) was examined by bioinformatics analysis and luciferase reporter assay. The protective effects of CRD on DN mice were evaluated by examining DN related biochemical indicators and renal histopathology. Results In response to HG, the level of miR-193b-5p was elevated, whilst the level of MCL-1 was downregulated, and CRD therapy reversed this behavior. MCL-1 was further identified to be miR-193b-5p target. CRD attenuated HG-induced cell damage, inflammation and abnormal energy metabolism. Mechanistic investigations on in vitro models confirmed that protective effect of CRD against HG challenge to HK-2 cells is mediated through the regulation of expression of miR-193b-5p/MCL-1 axis. By examining DN related biochemical markers and renal histopathology, the protective effects of CRD on DN mice was assessed. Conclusions In summary, CRD decreased oxidative stress and inflammation by increasing miR-193b-5p and inactivating downstream MCL-1 in DN, hinting the pivotal values of CRD and miR-193b-5p in the management of DN. |
| first_indexed | 2024-03-09T14:55:05Z |
| format | Article |
| id | doaj.art-4b50cc5238c1412e84422e411d06fafb |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-03-09T14:55:05Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-4b50cc5238c1412e84422e411d06fafb2023-11-26T14:13:57ZengBMCChinese Medicine1749-85462023-10-0118111910.1186/s13020-023-00842-5Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axisRong Zheng0Weijie Zhang1Jufang Song2Yifei Zhong3Rong Zhu4Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineAbstract Background Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were used to evaluate the diagnostic value of CRD. Methods Quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence analysis, and immunohistochemical staining were used to assess changes in mRNA and protein expression. Oxidative stress was evaluated by detecting the production of reactive oxygen species (ROS) and the activity of antioxidant enzymes. Cell apoptosis was detected by the TUNEL and flow cytometric methods. The interaction of miR-193b-5p and myeloid leukemia 1 (MCL-1) was examined by bioinformatics analysis and luciferase reporter assay. The protective effects of CRD on DN mice were evaluated by examining DN related biochemical indicators and renal histopathology. Results In response to HG, the level of miR-193b-5p was elevated, whilst the level of MCL-1 was downregulated, and CRD therapy reversed this behavior. MCL-1 was further identified to be miR-193b-5p target. CRD attenuated HG-induced cell damage, inflammation and abnormal energy metabolism. Mechanistic investigations on in vitro models confirmed that protective effect of CRD against HG challenge to HK-2 cells is mediated through the regulation of expression of miR-193b-5p/MCL-1 axis. By examining DN related biochemical markers and renal histopathology, the protective effects of CRD on DN mice was assessed. Conclusions In summary, CRD decreased oxidative stress and inflammation by increasing miR-193b-5p and inactivating downstream MCL-1 in DN, hinting the pivotal values of CRD and miR-193b-5p in the management of DN.https://doi.org/10.1186/s13020-023-00842-5Cordycepin (CRD)Diabetic nephropathy (DN)miR-193b-5p/MCL-1 axisInflammationOxidative stress |
| spellingShingle | Rong Zheng Weijie Zhang Jufang Song Yifei Zhong Rong Zhu Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis Chinese Medicine Cordycepin (CRD) Diabetic nephropathy (DN) miR-193b-5p/MCL-1 axis Inflammation Oxidative stress |
| title | Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis |
| title_full | Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis |
| title_fullStr | Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis |
| title_full_unstemmed | Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis |
| title_short | Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis |
| title_sort | cordycepin from cordyceps militaris ameliorates diabetic nephropathy via the mir 193b 5p mcl 1 axis |
| topic | Cordycepin (CRD) Diabetic nephropathy (DN) miR-193b-5p/MCL-1 axis Inflammation Oxidative stress |
| url | https://doi.org/10.1186/s13020-023-00842-5 |
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