Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway
Context Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated.Objective This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms....
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Pharmaceutical Biology |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/13880209.2022.2112239 |
| _version_ | 1828408032868958208 |
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| author | Jialin Li Jiawen Zhang Meng Yang Xiaocui Huang Meng Zhang Xiansong Fang Suzhen Wu |
| author_facet | Jialin Li Jiawen Zhang Meng Yang Xiaocui Huang Meng Zhang Xiansong Fang Suzhen Wu |
| author_sort | Jialin Li |
| collection | DOAJ |
| description | Context Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated.Objective This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms.Materials and methods The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-β1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups (n = 10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n = 10) was included as the control.Results Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro. After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo, respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion.Discussion and conclusions Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol. |
| first_indexed | 2024-12-10T11:33:42Z |
| format | Article |
| id | doaj.art-8c85a54a7b2943439e3ddf34fe8b75e1 |
| institution | Directory Open Access Journal |
| issn | 1388-0209 1744-5116 |
| language | English |
| last_indexed | 2024-12-10T11:33:42Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Pharmaceutical Biology |
| spelling | doaj.art-8c85a54a7b2943439e3ddf34fe8b75e12022-12-22T01:50:30ZengTaylor & Francis GroupPharmaceutical Biology1388-02091744-51162022-12-016011690170010.1080/13880209.2022.2112239Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathwayJialin Li0Jiawen Zhang1Meng Yang2Xiaocui Huang3Meng Zhang4Xiansong Fang5Suzhen Wu6Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaSchool of Basic Medicine, Gannan Medical University, Ganzhou, ChinaFirst Affiliated Hospital, Gannan Medical University, Ganzhou, ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, ChinaContext Kirenol possesses anti-inflammatory, antifibrotic and anti-arthritic effects. However, its reno-protective effects against diabetic nephropathy (DN) have not been evaluated.Objective This study explores the reno-protective effects of kirenol against DN and clarifies the potential mechanisms.Materials and methods The mesangial cells were treated with 20 µM kirenol and 10 ng/mL human recombinant TGF-β1 or 30 mM glucose for 24 h. Then the cells were harvested to assay the expression of the target genes or proteins. Thirty C57BL/6J male mice were given high-fat diet with streptozotocin injection to induce diabetes and then were randomized into three groups (n = 10): vehicle administration (DM group), 2 mg/kg kirenol (DM + kirenol group) and 200 mg/kg metformin (Met group) for 3 months, orally. A healthy group (Con, n = 10) was included as the control.Results Compared to the DM group, kirenol treatment decreased the phosphorylation of Smad2/3 and NF-κB (0.64- and 0.43-fold) as well as the accumulation of FN and Col IV (0.58- and 0.35-fold); moreover, the expression of IκBα was restored to normal level by kirenol treatment both in vivo and in vitro. After kirenol treatment, IL-6 expression was decreased 0.35- and 0.57-fold, and TNF-α expression was decreased 0.34- and 0.46-fold, in vitro and in vivo, respectively. Furthermore, kirenol alleviated the glomerular basement membrane thickness and foot process fusion.Discussion and conclusions Kirenol could alleviate DN by downregulating the TGF-β/Smads and the NF-κB signal pathway. Our study provides a potential mechanism for the treatment of DN with kirenol.https://www.tandfonline.com/doi/10.1080/13880209.2022.2112239TNF-αIL-6mesangial cellsfibronectincollagen IV |
| spellingShingle | Jialin Li Jiawen Zhang Meng Yang Xiaocui Huang Meng Zhang Xiansong Fang Suzhen Wu Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway Pharmaceutical Biology TNF-α IL-6 mesangial cells fibronectin collagen IV |
| title | Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway |
| title_full | Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway |
| title_fullStr | Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway |
| title_full_unstemmed | Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway |
| title_short | Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway |
| title_sort | kirenol alleviates diabetic nephropathy via regulating tgf β smads and the nf κb signal pathway |
| topic | TNF-α IL-6 mesangial cells fibronectin collagen IV |
| url | https://www.tandfonline.com/doi/10.1080/13880209.2022.2112239 |
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