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Oleanolic acid attenuates hydrogen peroxide-induced apoptosis of IPEC-J2 cells through suppressing c-Jun and MAPK
Mingyang Hu1, Lei Zhang1, Hongpeng Jia1
1Laboratory of Molecular Nutrition and Immunity, College of Animal Science and Technology, Northeast Agricultural University, Harbin, People's Republic of China.
Abstract:
Oleanolic acid (OA) is a natural triterpenoid with therapeutic potential for a multitude of diseases. However, the precise mechanism by which OA influences stress-induced apoptosis of intestinal epithelial cells remains elusive. Therefore, the effect of OA on intestinal diseases under stressful conditions and its possible mechanisms have been investigated. In a hydrogen peroxide (H2 O2 )-induced oxidative stress model, OA attenuated H2 O2 -induced apoptosis in a concentration-dependent manner. To investigate the underlying mechanisms, the gene expression profile of OA on IPEC-J2 cells was analyzed using an RNA sequencing system. Results from gene ontology and Kyoto encyclopedia of genes and genomes analysis confirmed that OA may mitigate the cytotoxic effects of H2 O2 by downregulating gene expression through the MAPK signaling pathway. Furthermore, Quantitative real-time polymerase chain reaction results validated the differentially expressed genes data. Western blot analysis further demonstrated that OA effectively suppressed the expression level of c-Jun protein induced by H2 O2 in IPEC-J2 cells. Collectively, our results indicate that OA pretreatment significantly attenuated H2 O2 -induced apoptosis in intestinal epithelial cells through suppressing c-Jun and MAPK pathway.
Insights
Oleanolic acid (OA) protects intestinal cells from oxidative stress by reducing apoptosis. It achieves this by downregulating the c-Jun and MAPK signaling pathways, offering therapeutic potential for intestinal diseases.
Area of Science:
- Cell Biology
- Molecular Biology
- Pharmacology
Background:
- Oleanolic acid (OA) is a natural triterpenoid with broad therapeutic potential.
- The exact mechanisms by which OA affects stress-induced apoptosis in intestinal epithelial cells are not fully understood.
- Intestinal epithelial cells are vulnerable to oxidative stress, which can lead to apoptosis and disease.
Purpose of the Study:
- To investigate the protective effects of Oleanolic acid (OA) against oxidative stress in intestinal epithelial cells.
- To elucidate the underlying molecular mechanisms of OA's action in an oxidative stress model.
- To determine OA's impact on stress-induced apoptosis and related signaling pathways.
Main Methods:
- An in vitro model of oxidative stress was created using hydrogen peroxide (H₂O₂) in IPEC-J2 intestinal cells.
- Gene expression profiling was performed using RNA sequencing.
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to validate gene and protein expression levels.
Main Results:
- Oleanolic acid (OA) demonstrated a concentration-dependent attenuation of H₂O₂-induced apoptosis in intestinal cells.
- RNA sequencing and pathway analysis indicated that OA mitigates H₂O₂ cytotoxicity by downregulating gene expression via the MAPK signaling pathway.
- Western blot analysis confirmed that OA suppressed the H₂O₂-induced expression of c-Jun protein.
Conclusions:
- Oleanolic acid (OA) pretreatment significantly protects intestinal epithelial cells against H₂O₂-induced apoptosis.
- The protective effect is mediated by the suppression of the c-Jun protein and the MAPK signaling pathway.
- OA shows promise as a therapeutic agent for managing intestinal diseases associated with oxidative stress.
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