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Oleanolic acid inhibits mesangial cell proliferation and inflammatory response in mesangial proliferative
Dan Pan1, Jikai Xia2, Yilun Qu3
1Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China; The College Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Background:
Mesangial proliferative glomerulonephritis (MsPGN) is a common form of glomerulonephritis characterized by mesangial cell proliferation and inflammatory responses. However, current clinical treatment options for MsPGN are rather limited. Oleanolic acid (OA), a natural pentacyclic triterpenoid compound, exhibits anti-tumor and anti-inflammatory properties and has been proven to have renal protective effects. We speculate that OA could potentially serve as an alternative therapy for MsPGN.
Objective:
This study aimed to investigate the therapeutic efficacy and mechanism of OA against MsPGN.
Methods:
Tail vein injection of anti-Thy1 antibody was used to establish the MsPGN model, followed by a comprehensive assessment of the effects of OA on renal function, histopathological changes, and inflammatory responses in anti-Thy1 nephritis rats. Subsequently, network pharmacology was employed to predict the key targets and pathways of OA in treating MsPGN. Finally, in vivo and in vitro experiments were conducted to validate the results of network pharmacology.
Results:
OA significantly improved renal function, and attenuated mesangial cell proliferation and inflammatory reactions in anti-Thy1 nephritis rats. Network pharmacology analysis identified TNF-α, IL-6, IL-1β, MAPK3, and AKT1 as key targets of OA in the treatment of MsPGN, and involved the IL-17 signaling pathway. Additionally, we observed increased phosphorylation levels of ERK and AKT, as well as activation of downstream inflammatory responses, in both anti-Thy1 nephritis rats and mesangial cells stimulated with IL-17. In contrast, treatment with OA and the ERK inhibitor PD98059 reversed these effects. Furthermore, we identified IL17RA within this pathway as a potential target of OA.
Conclusions:
Our study demonstrates that OA can modulate the IL-17/ERK/AKT signaling pathway, thereby improving anti-Thy1 antibody-induced MsPGN. This establishes a theoretical basis for OA to potentially serve as a therapeutic agent for treating MsPGN.
Insights
Oleanolic acid (OA) effectively treats mesangial proliferative glomerulonephritis (MsPGN) by modulating the IL-17/ERK/AKT pathway. This natural compound shows promise as a novel therapeutic agent for MsPGN.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Mesangial proliferative glomerulonephritis (MsPGN) is a prevalent kidney disease with limited treatment options.
- Oleanolic acid (OA), a natural compound, possesses anti-inflammatory and renal-protective properties.
- OA is a potential candidate for alternative MsPGN therapy.
Purpose of the Study:
- To investigate the therapeutic effects of Oleanolic acid (OA) on MsPGN.
- To elucidate the underlying mechanism of OA in treating MsPGN.
Main Methods:
- An anti-Thy1 antibody-induced rat model of MsPGN was established.
- OA's effects on renal function, histology, and inflammation were assessed.
- Network pharmacology predicted OA's targets and pathways, validated by in vivo and in vitro experiments.
Main Results:
- OA treatment significantly improved renal function and reduced mesangial cell proliferation and inflammation in MsPGN rats.
- Network pharmacology identified key targets (TNF-α, IL-6, IL-1β, MAPK3, AKT1) and the IL-17 signaling pathway.
- OA modulated the IL-17/ERK/AKT pathway, with IL17RA identified as a potential target.
Conclusions:
- Oleanolic acid (OA) effectively ameliorates anti-Thy1 antibody-induced MsPGN.
- OA exerts its therapeutic effects by modulating the IL-17/ERK/AKT signaling pathway.
- OA presents a promising theoretical basis for its use as a therapeutic agent for MsPGN.
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