Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway

Objectives This study investigates whether curcumin/piperine (C/P) modulates butyrate levels and mitigates diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods Eight-week-old mice were treated with C/P for 12 weeks...

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Main Authors: Yinan Zhu, Lina Sun, Zhaoan Guo, Peiqing Xin, Feng Huang, Lei Song, Yulin Man, Miaomiao Ren, Zhongwei Ma, Ying Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2538117
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author Yinan Zhu
Lina Sun
Zhaoan Guo
Peiqing Xin
Feng Huang
Lei Song
Yulin Man
Miaomiao Ren
Zhongwei Ma
Ying Wang
author_facet Yinan Zhu
Lina Sun
Zhaoan Guo
Peiqing Xin
Feng Huang
Lei Song
Yulin Man
Miaomiao Ren
Zhongwei Ma
Ying Wang
author_sort Yinan Zhu
collection DOAJ
description Objectives This study investigates whether curcumin/piperine (C/P) modulates butyrate levels and mitigates diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods Eight-week-old mice were treated with C/P for 12 weeks, fecal samples were analyzed for short-chain fatty acids, and inflammatory markers in blood and kidneys were measured. Pathological staining and microscopy assessed the kidney and intestinal tissue morphology. Immunohistochemical detection of the expression of inflammatory markers in the kidneys and intestines. In vitro, the human proximal renal tubular cell line (HK-2) cells were exposed to high glucose (HG) and pretreated with C/P and sodium butyrate (NaB) to observe changes in inflammatory and oxidative stress markers. ML385 helped assess the role of the Nrf2/HO-1 pathway in the effects of C/P and NaB on inflammation and oxidative stress in DKD.Results Curcumin/piperine significantly improved renal injury and intestinal structural integrity, upregulated the expression of macrophage antigen CD68 and other inflammatory markers in the kidneys, and increased NaB levels in feces (p < .05). High glucose conditions enhanced inflammation and oxidative stress in HK-2 cells, whereas C/P and NaB pretreatment significantly inhibited these effects, reducing interleukin-6, IL-1β and other markers (p < .05), and increasing Nrf2 and HO-1 expression. Nrf2 inhibitor ML385 reduces the expression of Nrf2 and HO-1, and weakens the beneficial effects of C/P and NaB on HK-2 cells.Conclusions Curcumin/piperine enhances renal and intestinal integrity and modulates NaB levels to alleviate DKD through the Nrf2/HO-1 signaling pathway.
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series Renal Failure
spelling doaj-art-ab71a982dc034e0a9677872d12cdd25f2025-08-20T03:59:36ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2538117Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathwayYinan Zhu0Lina Sun1Zhaoan Guo2Peiqing Xin3Feng Huang4Lei Song5Yulin Man6Miaomiao Ren7Zhongwei Ma8Ying Wang9School of Clinical Medicine, Shandong Second Medical University, Weifang, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaSchool of Clinical Medicine, Shandong Second Medical University, Weifang, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaDepartment of Nephrology, Linyi People’s Hospital, Linyi, ChinaObjectives This study investigates whether curcumin/piperine (C/P) modulates butyrate levels and mitigates diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.Methods Eight-week-old mice were treated with C/P for 12 weeks, fecal samples were analyzed for short-chain fatty acids, and inflammatory markers in blood and kidneys were measured. Pathological staining and microscopy assessed the kidney and intestinal tissue morphology. Immunohistochemical detection of the expression of inflammatory markers in the kidneys and intestines. In vitro, the human proximal renal tubular cell line (HK-2) cells were exposed to high glucose (HG) and pretreated with C/P and sodium butyrate (NaB) to observe changes in inflammatory and oxidative stress markers. ML385 helped assess the role of the Nrf2/HO-1 pathway in the effects of C/P and NaB on inflammation and oxidative stress in DKD.Results Curcumin/piperine significantly improved renal injury and intestinal structural integrity, upregulated the expression of macrophage antigen CD68 and other inflammatory markers in the kidneys, and increased NaB levels in feces (p < .05). High glucose conditions enhanced inflammation and oxidative stress in HK-2 cells, whereas C/P and NaB pretreatment significantly inhibited these effects, reducing interleukin-6, IL-1β and other markers (p < .05), and increasing Nrf2 and HO-1 expression. Nrf2 inhibitor ML385 reduces the expression of Nrf2 and HO-1, and weakens the beneficial effects of C/P and NaB on HK-2 cells.Conclusions Curcumin/piperine enhances renal and intestinal integrity and modulates NaB levels to alleviate DKD through the Nrf2/HO-1 signaling pathway.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2538117Diabetic kidney diseasecurcuminpiperineinflammationoxidative stressNrf2/HO-1 signaling pathway
spellingShingle Yinan Zhu
Lina Sun
Zhaoan Guo
Peiqing Xin
Feng Huang
Lei Song
Yulin Man
Miaomiao Ren
Zhongwei Ma
Ying Wang
Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
Renal Failure
Diabetic kidney disease
curcumin
piperine
inflammation
oxidative stress
Nrf2/HO-1 signaling pathway
title Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
title_full Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
title_fullStr Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
title_full_unstemmed Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
title_short Curcumin/piperine modulates the butyrate levels and alleviates diabetic kidney disease via Nrf2/HO-1 signaling pathway
title_sort curcumin piperine modulates the butyrate levels and alleviates diabetic kidney disease via nrf2 ho 1 signaling pathway
topic Diabetic kidney disease
curcumin
piperine
inflammation
oxidative stress
Nrf2/HO-1 signaling pathway
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2538117
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