Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease

Objective: To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses. Methods: Adriamycin (ADR) combined with hydrocortisone (HC) was used...

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Main Authors: Pengfei Zheng, Yunhua Liu, Xinjiang Zhang, Tingting Jiao, Yingjie Wu, Mengmeng Zhang, Xinxue Zhang, Zongjiang Zhao
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:Journal of Traditional Chinese Medical Sciences
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2095754823000017
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author Pengfei Zheng
Yunhua Liu
Xinjiang Zhang
Tingting Jiao
Yingjie Wu
Mengmeng Zhang
Xinxue Zhang
Zongjiang Zhao
author_facet Pengfei Zheng
Yunhua Liu
Xinjiang Zhang
Tingting Jiao
Yingjie Wu
Mengmeng Zhang
Xinxue Zhang
Zongjiang Zhao
author_sort Pengfei Zheng
collection DOAJ
description Objective: To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses. Methods: Adriamycin (ADR) combined with hydrocortisone (HC) was used to induce CKD with KYDP in rats. ADR was injected into the tail vein twice. HC was injected intramuscularly for 8 weeks. ZWD was administered by gavage for 8 weeks. The general condition was observed, 24-h urine protein was detected, serum corticosterone, triiodothyronine, thyroxine, TSH, testosterone, cAMP, and cGMP levels were determined, and pathological analysis was conducted. Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes (DEGs), differentially expressed metabolites (DEMs), and differentially expressed pathways (DEPs). The core DEMs and DEGs were input to Metaboanalyst 5.0 to identify the pathways affected by ZWD. Results: In the HC group, KYDP symptoms were observed. Compared with control group, the levels of 24-h urine protein, TSH, and cGMP significantly increased (all P < .01), and corticosterone, triiodothyronine, thyroxine, and cAMP significantly decreased (all P < .01) in the HC group. After ZWD intervention, the levels of above-mentioned indicators could be reversed to some extent. Pathological analysis in the HC group revealed kidney lesions. DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways. In the ZWD group, differences in biosynthesis of unsaturated fatty acids and butanoate metabolism were observed. The following pathways were significantly affected by ZWD: arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism. Conclusion: ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism.
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spelling doaj.art-4c7c38f342e141978846463d536b0a3f2023-09-03T09:41:12ZengElsevierJournal of Traditional Chinese Medical Sciences2095-75482023-04-01102228243Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney diseasePengfei Zheng0Yunhua Liu1Xinjiang Zhang2Tingting Jiao3Yingjie Wu4Mengmeng Zhang5Xinxue Zhang6Zongjiang Zhao7School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaCorresponding author.; School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaObjective: To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses. Methods: Adriamycin (ADR) combined with hydrocortisone (HC) was used to induce CKD with KYDP in rats. ADR was injected into the tail vein twice. HC was injected intramuscularly for 8 weeks. ZWD was administered by gavage for 8 weeks. The general condition was observed, 24-h urine protein was detected, serum corticosterone, triiodothyronine, thyroxine, TSH, testosterone, cAMP, and cGMP levels were determined, and pathological analysis was conducted. Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes (DEGs), differentially expressed metabolites (DEMs), and differentially expressed pathways (DEPs). The core DEMs and DEGs were input to Metaboanalyst 5.0 to identify the pathways affected by ZWD. Results: In the HC group, KYDP symptoms were observed. Compared with control group, the levels of 24-h urine protein, TSH, and cGMP significantly increased (all P < .01), and corticosterone, triiodothyronine, thyroxine, and cAMP significantly decreased (all P < .01) in the HC group. After ZWD intervention, the levels of above-mentioned indicators could be reversed to some extent. Pathological analysis in the HC group revealed kidney lesions. DEGs in the ZWD group were mainly associated with pathways such as nucleotide synthesis and endocrine pathways. In the ZWD group, differences in biosynthesis of unsaturated fatty acids and butanoate metabolism were observed. The following pathways were significantly affected by ZWD: arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism. Conclusion: ZWD can be used to treat KYDP in CKD through regulating arachidonic acid metabolism, valine, leucine, and isoleucine biosynthesis, linoleic acid metabolism, and alpha-linolenic acid metabolism.http://www.sciencedirect.com/science/article/pii/S2095754823000017Chronic kidney diseaseKidney yang deficiency patternZhenwu decoctionTranscriptomicsMetabolomics
spellingShingle Pengfei Zheng
Yunhua Liu
Xinjiang Zhang
Tingting Jiao
Yingjie Wu
Mengmeng Zhang
Xinxue Zhang
Zongjiang Zhao
Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
Journal of Traditional Chinese Medical Sciences
Chronic kidney disease
Kidney yang deficiency pattern
Zhenwu decoction
Transcriptomics
Metabolomics
title Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
title_full Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
title_fullStr Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
title_full_unstemmed Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
title_short Transcriptomic and metabolomic analysis of the effects of Zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
title_sort transcriptomic and metabolomic analysis of the effects of zhenwu decoction on kidney yang deficiency pattern in chronic kidney disease
topic Chronic kidney disease
Kidney yang deficiency pattern
Zhenwu decoction
Transcriptomics
Metabolomics
url http://www.sciencedirect.com/science/article/pii/S2095754823000017
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