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Potential Molecular Targets of Oleanolic Acid in Insulin Resistance and Underlying Oxidative Stress: A Systematic
Ángel Fernández-Aparicio1,2, María Correa-Rodríguez2,3, Jose M Castellano4
1Department of Nursing, Faculty of Health Sciences, Melilla Campus, University of Granada, 52005 Melilla, Spain.
Abstract:
Oleanolic acid (OA) is a natural triterpene widely found in olive leaves that possesses antioxidant, anti-inflammatory, and insulin-sensitizing properties, among others. These OA characteristics could be of special interest in the treatment and prevention of insulin resistance (IR), but greater in-depth knowledge on the pathways involved in these properties is still needed. We aimed to systematically review the effects of OA on the molecular mechanisms and signaling pathways involved in the development of IR and underlying oxidative stress in insulin-resistant animal models or cell lines. The bibliographic search was carried out on PubMed, Web of Science, Scopus, Cochrane, and CINHAL databases between January 2001 and May 2022. The electronic search produced 5034 articles but, after applying the inclusion criteria, 13 animal studies and 3 cell experiments were identified, using SYRCLE's Risk of Bias for assessing the risk of bias of the animal studies. OA was found to enhance insulin sensitivity and glucose uptake, and was found to suppress the hepatic glucose production, probably by modulating the IRS/PI3K/Akt/FoxO1 signaling pathway and by mitigating oxidative stress through regulating MAPK pathways. Future randomized controlled clinical trials to assess the potential benefit of OA as new therapeutic and preventive strategies for IR are warranted.
Insights
Oleanolic acid (OA), found in olive leaves, improves insulin sensitivity and glucose uptake. This natural compound may help manage insulin resistance by modulating key signaling pathways and reducing oxidative stress.
Area of Science:
- Pharmacology
- Biochemistry
- Molecular Biology
Background:
- Oleanolic acid (OA) is a natural triterpene with antioxidant, anti-inflammatory, and insulin-sensitizing properties.
- Insulin resistance (IR) is a metabolic condition requiring novel therapeutic strategies.
- Understanding OA's molecular mechanisms in IR is crucial for its therapeutic application.
Purpose of the Study:
- To systematically review the effects of OA on molecular mechanisms and signaling pathways in insulin resistance.
- To investigate OA's role in mitigating oxidative stress associated with IR.
- To identify relevant pathways modulated by OA in preclinical models of IR.
Main Methods:
- A systematic literature search was conducted across major scientific databases (PubMed, Web of Science, Scopus, Cochrane, CINHAL) from January 2001 to May 2022.
- Inclusion criteria were applied to 5034 retrieved articles, resulting in 13 animal studies and 3 cell experiments.
- Risk of bias assessment for animal studies was performed using SYRCLE's tool.
Main Results:
- Oleanolic acid demonstrated enhancement of insulin sensitivity and glucose uptake.
- OA was found to suppress hepatic glucose production.
- OA likely modulates the IRS/PI3K/Akt/FoxO1 signaling pathway and mitigates oxidative stress via MAPK pathways.
Conclusions:
- Oleanolic acid shows potential in improving insulin sensitivity and glucose metabolism.
- OA's mechanisms involve modulation of key signaling pathways and reduction of oxidative stress.
- Further randomized controlled clinical trials are warranted to evaluate OA for IR prevention and treatment.
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