Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation
Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not c...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023089223 |
| _version_ | 1827615916691554304 |
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| author | Lei Xiang Xiangsheng Cai Xiaoshan Zhao Yuanling Liu Ya Xiao Pingping Jiang Lianghong Yin Dan Song Xuefeng Jiang |
| author_facet | Lei Xiang Xiangsheng Cai Xiaoshan Zhao Yuanling Liu Ya Xiao Pingping Jiang Lianghong Yin Dan Song Xuefeng Jiang |
| author_sort | Lei Xiang |
| collection | DOAJ |
| description | Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not clarified. Thus, this study utilized network pharmacology, UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography - Mass Spectrometry) and animal experiments to reveal the mechanisms of QDDHG on DKD. Experimental procedure: Screening and retrieving active ingredients and corresponding targets of QDDHG on DKD through the TCMSP, ETCM, Disgenet, GeneCards, Omim and DrugBank databases. The PPI were performed with BioGrid, STRING, OmniPath, InWeb-IM. AutoDock Vina molecular docking module to estimate the validation from the compounds and target proteins. Free energy to estimate the binding affinity for identified compounds and target proteins. The ingredients of QDDHG were analyzed utilizing UHPLC-MS/MS. In vivo experiment with db/db mice were used to verify the targets and pathway predicted by network pharmacology. Results and conclusion: The results demonstrated that QDDHG has 18 active compounds and 13 target proteins of QDDHG exerted a crucial role in treatment of DKD. QDDHG affect the multiple biological processes included cellular response to lipid, response to oxidative stress, and various pathways, such as AGE-RAGE, PI3K-Akt, MAPK, TNF, EGFR, STAT3. The results of UHPLC-MS/MS showed that six ingredients predicted by network pharmacology were also verified in experiment. In vivo experiment verified the effects of QDDHG on protecting the renal function mainly through inhibited the expression of EGFR, STAT3 and pERK in the db/db mice. |
| first_indexed | 2024-03-09T09:18:27Z |
| format | Article |
| id | doaj.art-132b4c8c9970494faf1d9baebcb15c2e |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:18:27Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-132b4c8c9970494faf1d9baebcb15c2e2023-12-02T07:03:56ZengElsevierHeliyon2405-84402023-11-01911e21714Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validationLei Xiang0Xiangsheng Cai1Xiaoshan Zhao2Yuanling Liu3Ya Xiao4Pingping Jiang5Lianghong Yin6Dan Song7Xuefeng Jiang8Department of Nephrology Internal Medicine, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China; Clinical Laboratory, Guangzhou Cadre Health Management Center, Guangzhou No.11 People's Hospital, Guangzhou, 510530, China; Department of Nephrology Internal Medicine, University of Chinese Academy of Science-Shenzhen Hospital, 518107, Shenzhen, China; Corresponding author. Department of Nephrology Internal Medicine, The First Affiliated Hospital of Jinan University, No. 613, Huang-Pu Road West, Guangzhou, 510630, China.Clinical Laboratory, Guangzhou Cadre Health Management Center, Guangzhou No.11 People's Hospital, Guangzhou, 510530, ChinaSchool of Traditional Chinese Medicine, Southern Medical University, 510515, Guangzhou, ChinaAdministrative Department, Guangdong Women and Children Hospital, 510010, Guangzhou, ChinaSchool of Traditional Chinese Medicine, Jinan University, 510632, Guangzhou, ChinaDepartment of Traditional Chinese Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, 510062, Guangzhou, ChinaDepartment of Nephrology Internal Medicine, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China; Corresponding author.Department of Nephrology Internal Medicine, University of Chinese Academy of Science-Shenzhen Hospital, 518107, Shenzhen, China; Corresponding author.School of Traditional Chinese Medicine, Southern Medical University, 510515, Guangzhou, China; Corresponding author.Background and aim: Diabetic Kidney Disease (DKD) is a common microvascular complication of diabetes mellitus. Multi-center, randomized controlled trials have shown that Qidan Dihuang Granule (QDDHG) reduces the levels of albuminuria of DKD. However, the specific mechanisms of QDDHG on DKD are not clarified. Thus, this study utilized network pharmacology, UHPLC-MS/MS (Ultra-High Performance Liquid Chromatography - Mass Spectrometry) and animal experiments to reveal the mechanisms of QDDHG on DKD. Experimental procedure: Screening and retrieving active ingredients and corresponding targets of QDDHG on DKD through the TCMSP, ETCM, Disgenet, GeneCards, Omim and DrugBank databases. The PPI were performed with BioGrid, STRING, OmniPath, InWeb-IM. AutoDock Vina molecular docking module to estimate the validation from the compounds and target proteins. Free energy to estimate the binding affinity for identified compounds and target proteins. The ingredients of QDDHG were analyzed utilizing UHPLC-MS/MS. In vivo experiment with db/db mice were used to verify the targets and pathway predicted by network pharmacology. Results and conclusion: The results demonstrated that QDDHG has 18 active compounds and 13 target proteins of QDDHG exerted a crucial role in treatment of DKD. QDDHG affect the multiple biological processes included cellular response to lipid, response to oxidative stress, and various pathways, such as AGE-RAGE, PI3K-Akt, MAPK, TNF, EGFR, STAT3. The results of UHPLC-MS/MS showed that six ingredients predicted by network pharmacology were also verified in experiment. In vivo experiment verified the effects of QDDHG on protecting the renal function mainly through inhibited the expression of EGFR, STAT3 and pERK in the db/db mice.http://www.sciencedirect.com/science/article/pii/S2405844023089223Qidan Dihuang GranuleDiabetic kidney diseaseNetwork pharmacologyExperimental verificationTraditional Chinese medicine |
| spellingShingle | Lei Xiang Xiangsheng Cai Xiaoshan Zhao Yuanling Liu Ya Xiao Pingping Jiang Lianghong Yin Dan Song Xuefeng Jiang Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation Heliyon Qidan Dihuang Granule Diabetic kidney disease Network pharmacology Experimental verification Traditional Chinese medicine |
| title | Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation |
| title_full | Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation |
| title_fullStr | Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation |
| title_full_unstemmed | Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation |
| title_short | Uncovering the mechanism of Qidan Dihuang Granule in the treatment of diabetic kidney disease combined network pharmacology, UHPLC-MS/MS with experimental validation |
| title_sort | uncovering the mechanism of qidan dihuang granule in the treatment of diabetic kidney disease combined network pharmacology uhplc ms ms with experimental validation |
| topic | Qidan Dihuang Granule Diabetic kidney disease Network pharmacology Experimental verification Traditional Chinese medicine |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023089223 |
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