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Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis.

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Title: Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis.
Authors: Pan F; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China., Lu J; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China., Ye G; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China., Zhu H; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China., Ma H; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China., Li J; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China., Yang X; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China., Yang H; Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.; Tianjin University of Traditional Chinese Medicine, Tianjin, China., Tong A; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.
Source: Clinical and experimental pharmacology & physiology [Clin Exp Pharmacol Physiol] 2026 Sep; Vol. 53 (9), pp. e70151.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Wiley-Blackwell Country of Publication: Australia NLM ID: 0425076 Publication Model: Print Cited Medium: Internet ISSN: 1440-1681 (Electronic) Linking ISSN: 03051870 NLM ISO Abbreviation: Clin Exp Pharmacol Physiol Subsets: MEDLINE
Imprint Name(s): Publication: Oxford, England : Wiley-Blackwell
Original Publication: Oxford, Blackwell Scientific Publications.
MeSH Terms: MicroRNAs*/genetics , MicroRNAs*/metabolism , Exosomes*/drug effects , Exosomes*/metabolism , Exosomes*/genetics , Drugs, Chinese Herbal*/pharmacology , Drugs, Chinese Herbal*/therapeutic use , Ferroptosis*/drug effects , Epithelial Cells*/drug effects , Epithelial Cells*/pathology , Epithelial Cells*/metabolism , Heme Oxygenase-1*/metabolism , Heme Oxygenase-1*/genetics , Kidney Tubules*/pathology , Kidney Tubules*/drug effects , Endothelial Cells*/drug effects , Endothelial Cells*/metabolism , Endothelial Cells*/pathology , Membrane Proteins*/metabolism , Membrane Proteins*/genetics, Animals ; Fibrosis ; Mice ; Male ; Capsules ; Mice, Inbred C57BL
Abstract: Objective: Chronic renal failure (CRF) represents the advanced stage of chronic kidney disease, for which no specific pharmacological treatments are currently available. Traditional Chinese medicine has demonstrated notable efficacy in managing CRF. Shengqingjiangzhuo capsules (SQJZ capsules), a traditional Chinese medicinal formulation, are employed clinically in the treatment of CRF. However, the precise mechanisms underlying its therapeutic effects remain insufficiently understood.
Methods: The SQJZ capsule's chemical components were identified using UPLC-Q-Exactive-Orbitrap-MS. TGFβ1-induced GECs and adenine-induced CRF models in mice were developed. Exosome miRNA sequencing, quantitative polymerase chain reaction (qPCR), Western blot and dual-luciferase reporter assays explored the interaction between miR-31-5p and HO-1, and their effects on ferroptosis markers (ROS, GSH, MDA, Fe2+, SLC7A11, GCLC), mitochondrial membrane potential and fibrosis markers α-SMA and collagen I.
Results: This study is the first to employ UPLC-Q-Exactive-Orbitrap-MS technology to analyse SQJZ capsules, identifying 82 active components. It indicates that TGF-β1-stimulated GECs-derived exosomes increase miR-31-5p in TECs, causing HO-1 inhibition and ferroptosis. The active drug in SQJZ capsules serum counteracts these effects, suggesting anti-ferroptosis and anti-fibrosis properties and improving renal function in cell and CRF animal models. Overall, SQJZ capsules reduce renal fibrosis by modulating the miR-31-5p/HO-1 axis and inhibiting ferroptosis in TECs.
Conclusion: SQJZ capsules is associated with amelioration of renal fibrosis by suppressing GECs-derived exosomal miR-31-5p, which derepresses HO-1 expression in TECs, thereby inhibiting ferroptosis and subsequent renal fibrosis.
(© 2026 John Wiley & Sons Australia, Ltd.)
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Grant Information: 2022AAC05053 Natural Science Foundation of Ningxia Province; Zyyzdxk-2023210 high-level key discipline construction project of National Administration of Traditional Chinese Medicine of China; 2022BEG02036 the key Research and Development Program of Ningxia Hui Autonomous Region
Contributed Indexing: Keywords: Shengqingjiangzhuo capsules; endothelial cells; epithelial cells; exosomes; fibrosis
Substance Nomenclature: 0 (MicroRNAs)
0 (Drugs, Chinese Herbal)
0 (Capsules)
EC 1.14.14.18 (Heme Oxygenase-1)
0 (Membrane Proteins)
EC 1.14.14.18 (Hmox1 protein, mouse)
Entry Date(s): Date Created: 20260828 Date Completed: 20260828 Latest Revision: 20260830
Update Code: 20260830
PubMed Central ID: PMC13522403
DOI: 10.1111/1440-1681.70151
PMID: 42661282
Database: MEDLINE
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Text:
  Availability: 0
Header DbId: cmedm
DbLabel: MEDLINE
An: 42661282
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Pan+F%22">Pan F</searchLink>; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Lu+J%22">Lu J</searchLink>; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Ye+G%22">Ye G</searchLink>; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Zhu+H%22">Zhu H</searchLink>; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Ma+H%22">Ma H</searchLink>; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Li+J%22">Li J</searchLink>; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Yang+X%22">Yang X</searchLink>; College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.<br /><searchLink fieldCode="AU" term="%22Yang+H%22">Yang H</searchLink>; Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.; National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.; Tianjin University of Traditional Chinese Medicine, Tianjin, China.<br /><searchLink fieldCode="AU" term="%22Tong+A%22">Tong A</searchLink>; Department of Nephrology, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Ningxia Hui Autonomous Region Academy of Traditional Chinese Medicine, Yinchuan, Ningxia, China.
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  Data: <searchLink fieldCode="JN" term="%220425076%22">Clinical and experimental pharmacology & physiology</searchLink> [Clin Exp Pharmacol Physiol] 2026 Sep; Vol. 53 (9), pp. e70151.
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Wiley-Blackwell%22">Wiley-Blackwell </searchLink><i>Country of Publication: </i>Australia <i>NLM ID: </i>0425076 <i>Publication Model: </i>Print <i>Cited Medium: </i>Internet <i>ISSN: </i>1440-1681 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2203051870%22">03051870 </searchLink><i>NLM ISO Abbreviation: </i>Clin Exp Pharmacol Physiol <i>Subsets: </i>MEDLINE
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  Data: <i>Publication</i>: Oxford, England : Wiley-Blackwell<br /><i>Original Publication</i>: Oxford, Blackwell Scientific Publications.
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  Data: <searchLink fieldCode="MM" term="%22MicroRNAs%22">MicroRNAs*</searchLink>/<searchLink fieldCode="MM" term="%22MicroRNAs+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22MicroRNAs%22">MicroRNAs*</searchLink>/<searchLink fieldCode="MM" term="%22MicroRNAs+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Exosomes%22">Exosomes*</searchLink>/<searchLink fieldCode="MM" term="%22Exosomes+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Exosomes%22">Exosomes*</searchLink>/<searchLink fieldCode="MM" term="%22Exosomes+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Exosomes%22">Exosomes*</searchLink>/<searchLink fieldCode="MM" term="%22Exosomes+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Drugs%2C+Chinese+Herbal%22">Drugs, Chinese Herbal*</searchLink>/<searchLink fieldCode="MM" term="%22Drugs%2C+Chinese+Herbal+pharmacology%22">pharmacology</searchLink> <br /><searchLink fieldCode="MM" term="%22Drugs%2C+Chinese+Herbal%22">Drugs, Chinese Herbal*</searchLink>/<searchLink fieldCode="MM" term="%22Drugs%2C+Chinese+Herbal+therapeutic+use%22">therapeutic use</searchLink> <br /><searchLink fieldCode="MM" term="%22Ferroptosis%22">Ferroptosis*</searchLink>/<searchLink fieldCode="MM" term="%22Ferroptosis+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Epithelial+Cells%22">Epithelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Epithelial+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Heme+Oxygenase-1%22">Heme Oxygenase-1*</searchLink>/<searchLink fieldCode="MM" term="%22Heme+Oxygenase-1+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Heme+Oxygenase-1%22">Heme Oxygenase-1*</searchLink>/<searchLink fieldCode="MM" term="%22Heme+Oxygenase-1+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%22">Kidney Tubules*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Kidney+Tubules%22">Kidney Tubules*</searchLink>/<searchLink fieldCode="MM" term="%22Kidney+Tubules+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Endothelial+Cells%22">Endothelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Endothelial+Cells+drug+effects%22">drug effects</searchLink> <br /><searchLink fieldCode="MM" term="%22Endothelial+Cells%22">Endothelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Endothelial+Cells+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Endothelial+Cells%22">Endothelial Cells*</searchLink>/<searchLink fieldCode="MM" term="%22Endothelial+Cells+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Membrane+Proteins%22">Membrane Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Membrane+Proteins+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Membrane+Proteins%22">Membrane Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Membrane+Proteins+genetics%22">genetics</searchLink><br /><searchLink fieldCode="MH" term="%22Animals%22">Animals</searchLink> ; <searchLink fieldCode="MH" term="%22Fibrosis%22">Fibrosis</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%22">Mice</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Capsules%22">Capsules</searchLink> ; <searchLink fieldCode="MH" term="%22Mice%2C+Inbred+C57BL%22">Mice, Inbred C57BL</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Objective: Chronic renal failure (CRF) represents the advanced stage of chronic kidney disease, for which no specific pharmacological treatments are currently available. Traditional Chinese medicine has demonstrated notable efficacy in managing CRF. Shengqingjiangzhuo capsules (SQJZ capsules), a traditional Chinese medicinal formulation, are employed clinically in the treatment of CRF. However, the precise mechanisms underlying its therapeutic effects remain insufficiently understood.<br />Methods: The SQJZ capsule's chemical components were identified using UPLC-Q-Exactive-Orbitrap-MS. TGFβ1-induced GECs and adenine-induced CRF models in mice were developed. Exosome miRNA sequencing, quantitative polymerase chain reaction (qPCR), Western blot and dual-luciferase reporter assays explored the interaction between miR-31-5p and HO-1, and their effects on ferroptosis markers (ROS, GSH, MDA, Fe<superscript>2+</superscript>, SLC7A11, GCLC), mitochondrial membrane potential and fibrosis markers α-SMA and collagen I.<br />Results: This study is the first to employ UPLC-Q-Exactive-Orbitrap-MS technology to analyse SQJZ capsules, identifying 82 active components. It indicates that TGF-β1-stimulated GECs-derived exosomes increase miR-31-5p in TECs, causing HO-1 inhibition and ferroptosis. The active drug in SQJZ capsules serum counteracts these effects, suggesting anti-ferroptosis and anti-fibrosis properties and improving renal function in cell and CRF animal models. Overall, SQJZ capsules reduce renal fibrosis by modulating the miR-31-5p/HO-1 axis and inhibiting ferroptosis in TECs.<br />Conclusion: SQJZ capsules is associated with amelioration of renal fibrosis by suppressing GECs-derived exosomal miR-31-5p, which derepresses HO-1 expression in TECs, thereby inhibiting ferroptosis and subsequent renal fibrosis.<br /> (© 2026 John Wiley & Sons Australia, Ltd.)
– Name: Ref
  Label: References
  Group: RefInfo
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– Name: GrantInfo
  Label: Grant Information
  Group: Grant
  Data: 2022AAC05053 Natural Science Foundation of Ningxia Province; Zyyzdxk-2023210 high-level key discipline construction project of National Administration of Traditional Chinese Medicine of China; 2022BEG02036 the key Research and Development Program of Ningxia Hui Autonomous Region
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Shengqingjiangzhuo capsules; endothelial cells; epithelial cells; exosomes; fibrosis
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (MicroRNAs)<br />0 (Drugs, Chinese Herbal)<br />0 (Capsules)<br />EC 1.14.14.18 (Heme Oxygenase-1)<br />0 (Membrane Proteins)<br />EC 1.14.14.18 (Hmox1 protein, mouse)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260828 <i>Date Completed: </i>20260828 <i>Latest Revision: </i>20260830
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260830
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13522403
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1111/1440-1681.70151
– Name: AN
  Label: PMID
  Group: ID
  Data: 42661282
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42661282
RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1111/1440-1681.70151
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: e70151
    Subjects:
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Fibrosis
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Capsules
        Type: general
      – SubjectFull: Mice, Inbred C57BL
        Type: general
      – SubjectFull: MicroRNAs genetics
        Type: general
      – SubjectFull: MicroRNAs metabolism
        Type: general
      – SubjectFull: Exosomes drug effects
        Type: general
      – SubjectFull: Exosomes metabolism
        Type: general
      – SubjectFull: Exosomes genetics
        Type: general
      – SubjectFull: Drugs, Chinese Herbal pharmacology
        Type: general
      – SubjectFull: Drugs, Chinese Herbal therapeutic use
        Type: general
      – SubjectFull: Ferroptosis drug effects
        Type: general
      – SubjectFull: Epithelial Cells drug effects
        Type: general
      – SubjectFull: Epithelial Cells pathology
        Type: general
      – SubjectFull: Epithelial Cells metabolism
        Type: general
      – SubjectFull: Heme Oxygenase-1 metabolism
        Type: general
      – SubjectFull: Heme Oxygenase-1 genetics
        Type: general
      – SubjectFull: Kidney Tubules pathology
        Type: general
      – SubjectFull: Kidney Tubules drug effects
        Type: general
      – SubjectFull: Endothelial Cells drug effects
        Type: general
      – SubjectFull: Endothelial Cells metabolism
        Type: general
      – SubjectFull: Endothelial Cells pathology
        Type: general
      – SubjectFull: Membrane Proteins metabolism
        Type: general
      – SubjectFull: Membrane Proteins genetics
        Type: general
    Titles:
      – TitleFull: Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis.
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            NameFull: Pan F
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            NameFull: Lu J
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            NameFull: Yang H
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            NameFull: Tong A
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          Dates:
            – D: 01
              M: 09
              Text: 2026 Sep
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1440-1681
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              Value: 53
            – Type: issue
              Value: 9
          Titles:
            – TitleFull: Clinical and experimental pharmacology & physiology
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