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The molecular mechanisms underpinning the therapeutic properties of oleanolic acid, its isomer and derivatives for type 2 diabetes and associated complications

Authors

  • Danielle Camer,

    1. Centre for Translational Neuroscience, School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
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  • Yinghua Yu,

    1. Centre for Translational Neuroscience, School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
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  • Alexander Szabo,

    1. Centre for Translational Neuroscience, School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
    2. ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, NSW, Australia
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  • Xu-Feng Huang

    Corresponding author
    1. Centre for Translational Neuroscience, School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW, Australia
    • Correspondence: Professor Xu-Feng Huang, Centre for Translational Neuroscience, School of Medicine, Illawarra Health and Medical Research Institute, University of Wollongong, NSW 2522, Australia

      E-mail: xhuang@uow.edu.au

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Abstract

Recent research has uncovered the molecular mechanisms responsible for the therapeutic properties of oleanolic acid (OA), its isomer ursolic acid (UA), and derivatives. In particular, recent reports have highlighted the benefits of these compounds in the prevention and treatment of type 2 diabetes and associated life-threatening complications, such as nonalcoholic fatty liver disease, nephropathy, retinopathy, and atherosclerosis. The prevalence of type 2 diabetes is of major concern since it is reaching global epidemic levels. Treatments targeting the signaling pathways altered in type 2 diabetes are being actively investigated, and OA and UA in natural and derivative forms are potential candidates to modulate these pathways. We will explore the findings from in vitro and in vivo studies showing that these compounds: (i) improve insulin signaling and reduce hyperglycemia; (ii) reduce oxidative stress by upregulating anti-oxidants and; (iii) reduce inflammation by inhibiting proinflammatory signaling. We will discuss the molecular mechanisms underpinning these therapeutic properties in this review in order to provide a rationale for the future use of OA, UA, and their derivatives for the prevention and treatment of type 2 diabetes and associated comorbidities.

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