Oleanolic acid, a small-molecule natural product, inhibits ECM degeneration in osteoarthritis by regulating the Hippo/YAP and Wnt/β-catenin pathways

Literature Information

Publication Date 2023-10-05
DOI 10.1039/D3FO01902K
Impact Factor 5.396
Authors

Chengwei Wei, Xiaopeng Song


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Abstract

Over the past few decades, osteoarthritis (OA) has been a major health problem worldwide. It is urgent to develop new, effective, and safe drugs to treat OA. There are many pentacyclic triterpenoids in nature that are safe and have health benefits. Oleanolic acid (OLA), one of the pentacyclic triterpenoids, is a potential novel compound for treating OA; however, its mechanism of action is still unclear. In this study, the mechanism of resistance to extracellular matrix (ECM) degradation of OLA and its protective role in the amelioration of OA were investigated by in vivo and in vitro experiments. We found that OLA promoted interleukin-1β (IL-1β)-induced production of type II collagen (collagen II) in rat chondrocytes, decreased the expression of matrix metalloproteinase (MMP)-3 and MMP-13, and inhibited inflammatory cytokine (IL-1β and TNF-α) and cartilage marker (CTX-II and COMP) levels, thereby hindering the pathological process of cartilage. Mechanistically, OLA inhibited the Wnt/β-catenin pathway, activated the Hippo/YAP pathway, and hampered the ECM degradation process by inhibiting the nuclear translocation of β-catenin and YAP. When we knocked down β-catenin, OLA lost its stimulatory effect on the Hippo pathway. These findings confirm that OLA plays an anti-ECM degradation role by regulating the Wnt/β-catenin and Hippo/YAP pathways. Overall, this study provides a theoretical basis for developing highly effective and low-toxic natural products for the prevention and treatment of OA.

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Food & Function

Food & Function
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Self-citation Rate: 3.9%
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Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish novel, cutting-edge, original research focussing on food, its nutrients and their relation to human health and nutrition. We welcome research describing the: Physical properties and structure of food and how this relates to sensory perception and human health Biochemical and physiological actions of food components Interactions between foods, gut microbiota and human physiology Nutritional and biological evaluation of food Clinical and population studies using food or food components Development of biomarkers of food intake and effects on human health We also welcome systematic reviews and meta-analyses of existing studies in the literature, provided these are objective and scientifically valid Food in this context is defined as materials of plant, animal or mineral origin, which are consumed orally (by humans) for pleasure and to sustain growth and vital processes. Examples of research topics that are of interest to be published in Food & Function are: Chemistry and physics of food components and digestion processes Relationship between the physical properties/structure of food and nutrition and human health - for example, impact of food matrix or processing on nutrient release and uptake Molecular properties and physiological effects of food components (nutrients, fibres, essential micronutrients, phytochemicals, bioactives, food substitutes, novel ingredients, allergens, flavours and fragrances) Nutritional and health effects of food including bioavailability and metabolism assessment of food components (nutrients, micronutrients and other microconstituents) Efficacy and mechanisms of food constituents in the body - including biomarkers of intakes, exposure and effects Impacts of foods/food components on gut microorganisms and human physiology - For example impact of fermented foods Role of nutrition and diet in human disease prevention and development Cellular and molecular effects/mechanisms of food/food components image block The following types of research are not within the scope of Food & Function: Research relating to traditional herbal medicines, medicinal plants or active compounds extracted from such plants (materials that are primarily consumed as medicine, i.e. the intended purpose is primarily to treat, cure or prevent a non-deficiency disease) or relating to foods not recognised as human diet contributors Animal nutrition research that is not primarily designed as a model to benefit human nutrition (for example, studies of growth/accretion, heat stress, weaning, ruminant digestion, meat quality, etc.) Treatments administered by non-oral routes such as injection (subcutaneous, intramuscular, intraperitoneal, etc.), dermal/transdermal, rectal, inhalation, nasal, etc. Exceptions are when such routes of administration are used for mechanistic/control purposes in the experimental design Pharmacological/pharmaceutical approaches: Encapsulation, emulsification and/or pure controlled release of compounds or bioactives that do not come directly from edible foods, such as dietary supplements - these are better suited to a pharmaceutical journal In vitro or in vivo studies with poorly defined (insufficiently characterised) extracts and studies without appropriate controls will not be considered Cells studies not considering the metabolism of food components ingested – for example, irrelevant exposure of cells to compounds not present in the body after absorption Manuscripts with only a fully theoretical/bioinformatic approach and without appropriate support from analytical evidence will not be considered for publication Studies focussing solely on food engineering, preservation and sustainable technologies – these can be published in our companion journal Sustainable Food Technology Pure food analysis - these can be published in Analytical Methods

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