Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology
Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients.Methods: We searched for available randomized controlled studies on DKD patients’ treatment with CaD through open databases. Continuous variables were expressed as standa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.850167/full |
| _version_ | 1798036923297562624 |
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| author | Bingyu Du Bingyu Du Bingyu Du Bingyu Du Yanyan Yin Yanyan Yin Yanyan Yin Yuqing Wang Hui Fu Helin Sun Zhaodi Yue Zhaodi Yue Shaohong Yu Shaohong Yu Shaohong Yu Zhongwen Zhang Zhongwen Zhang Zhongwen Zhang |
| author_facet | Bingyu Du Bingyu Du Bingyu Du Bingyu Du Yanyan Yin Yanyan Yin Yanyan Yin Yuqing Wang Hui Fu Helin Sun Zhaodi Yue Zhaodi Yue Shaohong Yu Shaohong Yu Shaohong Yu Zhongwen Zhang Zhongwen Zhang Zhongwen Zhang |
| author_sort | Bingyu Du |
| collection | DOAJ |
| description | Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients.Methods: We searched for available randomized controlled studies on DKD patients’ treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes.Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD.Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients. |
| first_indexed | 2024-04-11T21:19:37Z |
| format | Article |
| id | doaj.art-94e91398428e457480cd5c084b6ba42d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T21:19:37Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-94e91398428e457480cd5c084b6ba42d2022-12-22T04:02:42ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.850167850167Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacologyBingyu Du0Bingyu Du1Bingyu Du2Bingyu Du3Yanyan Yin4Yanyan Yin5Yanyan Yin6Yuqing Wang7Hui Fu8Helin Sun9Zhaodi Yue10Zhaodi Yue11Shaohong Yu12Shaohong Yu13Shaohong Yu14Zhongwen Zhang15Zhongwen Zhang16Zhongwen Zhang17Department of Endocrinology and Metabology, Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Clinical Medical College and Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaCollege of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Endocrinology and Metabology, Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Clinical Medical College and Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaCollege of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ChinaShandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, Shandong Institute of Nephrology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaThe Clinical Medical College, Cheeloo Medical College of Shandong University, Jinan, ChinaShandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, Shandong Institute of Nephrology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaCollege of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Endocrinology and Metabology, Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Clinical Medical College and Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Endocrinology and Metabology, Shandong University of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaDepartment of Rehabilitation Medicine, The Second Clinical Medical College and Medical College, Shandong University of Traditional Chinese Medicine, Jinan, ChinaShandong Key Laboratory of Rheumatic Disease and Translational Medicine, Department of Endocrinology and Metabology, Shandong Institute of Nephrology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, ChinaAims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients.Methods: We searched for available randomized controlled studies on DKD patients’ treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes.Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD.Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients.https://www.frontiersin.org/articles/10.3389/fphar.2022.850167/fullcalcium dobesilatediabetic kidney diseasenetwork pharmacologyMAPK signaling pathwaychemokine signaling pathway |
| spellingShingle | Bingyu Du Bingyu Du Bingyu Du Bingyu Du Yanyan Yin Yanyan Yin Yanyan Yin Yuqing Wang Hui Fu Helin Sun Zhaodi Yue Zhaodi Yue Shaohong Yu Shaohong Yu Shaohong Yu Zhongwen Zhang Zhongwen Zhang Zhongwen Zhang Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology Frontiers in Pharmacology calcium dobesilate diabetic kidney disease network pharmacology MAPK signaling pathway chemokine signaling pathway |
| title | Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| title_full | Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| title_fullStr | Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| title_full_unstemmed | Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| title_short | Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| title_sort | calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing mapk and chemokine signaling pathways based on clinical evaluation and network pharmacology |
| topic | calcium dobesilate diabetic kidney disease network pharmacology MAPK signaling pathway chemokine signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.850167/full |
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