Schisanhenol Alleviates Mycophenolic Acid-Induced Intestinal Epithelial Cell Barrier Damage by Activating the Nrf2/HO-1 Signaling Pathway

AuthorYiyun Dengen
AuthorJiawang Fanen
AuthorChunlan Yangen
AuthorYan Huangen
AuthorQingrong Xiaen
AuthorJun Liangen
AuthorDujuan Xuen
AuthorYan Duen
AuthorYong Suen
OrcidYong Su [0000-0002-2655-1412]en
Issued Date2025-12-31en
AbstractBackground: Reactive oxygen species (ROS)-mediated apoptosis of intestinal epithelial cells and tight junction (TJ) protein loss play critical roles in mycophenolic acid (MPA)-induced disruption of intestinal epithelial barrier function, yet no effective therapeutic strategies exist. Schisanhenol (Sal), a major component of the traditional Chinese medicine Wuzhi capsule, exhibits strong antioxidant activity. Objectives: The present study aimed to investigate the protective efficacy and mechanisms of Sal against MPA-induced damage to the intestinal mechanical barrier. Methods: Caco-2 cells were exposed to MPA (10 μM), Sal (5, 10, and 25 μM), or ML385 (2 μM) for 24 hours. Cell viability was measured via a Cell Counting Kit-8 (CCK-8) assay. The expression of apoptosis-related and TJ proteins was evaluated through Western blot analysis. Flow cytometry was used to quantify the percentage of apoptotic Caco-2 cells. Immunofluorescence assays were performed to assess the localization of TJ proteins. Intracellular ROS levels were measured using H2DCFDA staining. Oxidative and antioxidative biomarker levels were quantified using specific assay kits. Results: Sal significantly increased the viability of MPA-treated cells. It also upregulated Bcl-2 expression and reduced apoptosis. Furthermore, Sal increased the expression of the TJ proteins ZO-1 and occludin. Additionally, Sal upregulated the MPA-mediated decrease in Nrf2/HO-1 expression, reduced intracellular ROS accumulation, and increased the levels of antioxidants, including SOD, CAT, and GSH. However, ML385 partially abrogated the protective effects of Sal. Conclusions: Schisanhenol alleviates MPA-induced intestinal mechanical barrier damage via modulation of the Nrf2 signaling pathway, highlighting its antioxidant and antiapoptotic properties.en
DOIhttps://doi.org/10.5812/ijpr-161994en
URIhttps://brieflands.com/journals/ijpr/articles/161994en
KeywordSchisanhenolen
KeywordMycophenolic Aciden
KeywordTight Junctionsen
KeywordReactive Oxygen Speciesen
KeywordAntioxidanten
PublisherBrieflandsen
TitleSchisanhenol Alleviates Mycophenolic Acid-Induced Intestinal Epithelial Cell Barrier Damage by Activating the Nrf2/HO-1 Signaling Pathwayen
TypeResearch Articleen

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