Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway

IntroductionChronic kidney disease (CKD) is a chronic progressive disease characterized by abnormalities in kidney structure or function caused by variousfactors. It has become a significant public health problem, posing a threat to human health worldwide. Shenshuaikang enema (SSKE) has demonstrated...

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Main Authors: Yan Ye, Xiaopeng Huang, Xueying Li, Fei Gao, Wenzhen Zhong, Anqi Tang, Liangbin Zhao, Dengpiao Xie, Naijing Ye
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1453668/full
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author Yan Ye
Yan Ye
Xiaopeng Huang
Xiaopeng Huang
Xiaopeng Huang
Xueying Li
Xueying Li
Fei Gao
Wenzhen Zhong
Anqi Tang
Anqi Tang
Liangbin Zhao
Dengpiao Xie
Naijing Ye
Naijing Ye
author_facet Yan Ye
Yan Ye
Xiaopeng Huang
Xiaopeng Huang
Xiaopeng Huang
Xueying Li
Xueying Li
Fei Gao
Wenzhen Zhong
Anqi Tang
Anqi Tang
Liangbin Zhao
Dengpiao Xie
Naijing Ye
Naijing Ye
author_sort Yan Ye
collection DOAJ
description IntroductionChronic kidney disease (CKD) is a chronic progressive disease characterized by abnormalities in kidney structure or function caused by variousfactors. It has become a significant public health problem, posing a threat to human health worldwide. Shenshuaikang enema (SSKE) has demonstrated notable efficacy and safety in treating CKD, although its mechanism of action remains unclear.MethodsThe CKD rat model was induced using 2.5% adenine, and the effect of SSKE was evaluated by detecting uremic toxins, inflammatory cytokines, and renal function. The structure of the intestine and kidney was observed using electron microscopy. Pathological changes in the intestine and kidney were detected by H&E staining. The expression of Occludin, Claudin-1, and ZO-1 in the intestine was detected by immunohistochemistry. The degree of renal fibrosis was observed using Masson and PAS staining. The expression of NF-κB and MyD88 protein in the intestine, and the expression of F4/80, TLR4, NF-κB and MyD88 in the kidney were detected by immunofluorescence staining. NF-κB-RE-Luc transgenic mice were used to construct a CKD mouse model, and changes in fluorescence intensity in mice and isolated kidney tissues were detected within 1–6 days using a small animal live imager. Finally, 16S rRNA amplicon sequencing was used to monitor changes in intestinal flora in CKD patients before and after SSKE treatment.ResultsWe found that SSKE improves renal function, attenuates renal fibrosis, reduces inflammatory factor levels, and decreases damage to intestinal and renal structures in adenine-induced CKD rats. Additionally, our results suggest that SSKE regulates NF-κB pathways, increases the expression of tight junction proteins, improves intestinal permeability, promotes the growth of beneficial bacteria, inhibits the proliferation of harmful bacteria, and reduces metabolic disorders. Ultimately, these effects contribute to the efficacy of SSKE in treating CKD.ConclusionThese results indicate that SSKE restores intestinal barrier function by regulating the microbiota-gut-kidney axis, thereby treating CKD.
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spelling doaj-art-a9c21cc85c45404b9e71acc8fb020edc2025-01-21T04:11:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.14536681453668Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathwayYan Ye0Yan Ye1Xiaopeng Huang2Xiaopeng Huang3Xiaopeng Huang4Xueying Li5Xueying Li6Fei Gao7Wenzhen Zhong8Anqi Tang9Anqi Tang10Liangbin Zhao11Dengpiao Xie12Naijing Ye13Naijing Ye14TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Ministry of Science, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaSchool of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaState Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaTCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaHospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaIntroductionChronic kidney disease (CKD) is a chronic progressive disease characterized by abnormalities in kidney structure or function caused by variousfactors. It has become a significant public health problem, posing a threat to human health worldwide. Shenshuaikang enema (SSKE) has demonstrated notable efficacy and safety in treating CKD, although its mechanism of action remains unclear.MethodsThe CKD rat model was induced using 2.5% adenine, and the effect of SSKE was evaluated by detecting uremic toxins, inflammatory cytokines, and renal function. The structure of the intestine and kidney was observed using electron microscopy. Pathological changes in the intestine and kidney were detected by H&E staining. The expression of Occludin, Claudin-1, and ZO-1 in the intestine was detected by immunohistochemistry. The degree of renal fibrosis was observed using Masson and PAS staining. The expression of NF-κB and MyD88 protein in the intestine, and the expression of F4/80, TLR4, NF-κB and MyD88 in the kidney were detected by immunofluorescence staining. NF-κB-RE-Luc transgenic mice were used to construct a CKD mouse model, and changes in fluorescence intensity in mice and isolated kidney tissues were detected within 1–6 days using a small animal live imager. Finally, 16S rRNA amplicon sequencing was used to monitor changes in intestinal flora in CKD patients before and after SSKE treatment.ResultsWe found that SSKE improves renal function, attenuates renal fibrosis, reduces inflammatory factor levels, and decreases damage to intestinal and renal structures in adenine-induced CKD rats. Additionally, our results suggest that SSKE regulates NF-κB pathways, increases the expression of tight junction proteins, improves intestinal permeability, promotes the growth of beneficial bacteria, inhibits the proliferation of harmful bacteria, and reduces metabolic disorders. Ultimately, these effects contribute to the efficacy of SSKE in treating CKD.ConclusionThese results indicate that SSKE restores intestinal barrier function by regulating the microbiota-gut-kidney axis, thereby treating CKD.https://www.frontiersin.org/articles/10.3389/fphar.2024.1453668/fullchronic kidney disease (CKD)shenshuaikang enema (SSKE)microbiota-gutkidney axisNF-κB pathwayintestinal barrier
spellingShingle Yan Ye
Yan Ye
Xiaopeng Huang
Xiaopeng Huang
Xiaopeng Huang
Xueying Li
Xueying Li
Fei Gao
Wenzhen Zhong
Anqi Tang
Anqi Tang
Liangbin Zhao
Dengpiao Xie
Naijing Ye
Naijing Ye
Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
Frontiers in Pharmacology
chronic kidney disease (CKD)
shenshuaikang enema (SSKE)
microbiota-gutkidney axis
NF-κB pathway
intestinal barrier
title Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
title_full Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
title_fullStr Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
title_full_unstemmed Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
title_short Shenshuaikang enema restores the intestinal barrier and microbiota-gut-kidney axis balance to alleviate chronic kidney disease via NF-κB pathway
title_sort shenshuaikang enema restores the intestinal barrier and microbiota gut kidney axis balance to alleviate chronic kidney disease via nf κb pathway
topic chronic kidney disease (CKD)
shenshuaikang enema (SSKE)
microbiota-gutkidney axis
NF-κB pathway
intestinal barrier
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1453668/full
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