Abstract

Obesity is a major risk factor for type 2 diabetes mellitus development and is characterized by an abnormal expansion of adipose tissue and low-grade chronic inflammation that contribute to insulin resistance. Although there are multiple treatments, most therapies can produce undesirable side effects and therefore, new and effective treatments with fewer side effects are necessary. Previously, we demonstrated that a natural extract from the leaves of Eucalyptus tereticornis (OBE100) has anti-inflammatory, hypoglycemic and hypolipidemic activities. The major compounds identified in OBE100 were three pentacyclic triterpenoids, ursolic acid, oleanolic acid, and ursolic acid lactone. Triterpenoids have shown multiples biological activities. This current study compared the biological effect produced by OBE100 with five different reconstituted mixtures of these triterpenoids. Different cell lines were used to evaluate cytotoxicity, reactive oxygen species production, inflammatory cytokine expression, glucose uptake induction, leptin and adiponectin expression, and lipid accumulation. OBE100 treatment was the most efficacious and none of the formulated triterpenoid mixtures significantly improved on this. Moreover, OBE100 was less toxic and reduced reactive oxygen species production. Our study showed that the proven beneficial properties of triterpenoids may be enhanced due to the interaction with minor secondary metabolites present in the natural extract improving their anti-inflammatory properties.

Highlights

  • According to a 2018 World Health Organization report, worldwide obesity has nearly tripled since 1975

  • Effect of triterpenoid mixtures on J774A.1 macrophage cell line Macrophage cell viability was affected by OBE100, M2, and M4; these treatments all have a high concentration of ursolic acid lactone (UAL) and produced less than a 20% reduction in viability of J774A.1 cells

  • We have previously determined that ursolic acid (UA), oleanolic acid (OA), and UAL are the major compounds identified in the OBE100 raw fraction

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Summary

Introduction

According to a 2018 World Health Organization report, worldwide obesity has nearly tripled since 1975. Over 1.9 billion people are obese or overweight, including 340 million children and adolescents (WHO 2018). Obesity is accompanied by low-grade inflammation that explains metabolic complications linked to increases in weight. Inflammation may play a causative role in generating insulin resistance, defective insulin secretion and disruption of other aspects of energy homeostasis in type 2 diabetes mellitus (T2DM) development (Donath & Shoelson 2011, Saltiel & Olefsky 2017). Reducing body weight using pharmacotherapy may provide benefits by lowering the risk of obesity-associated comorbidities; many weight-loss therapies present serious adverse effects and only a few are commercially available (Krentz et al 2016). Antihyperglycemic agents have similar problems, resulting in side effects or nonadherence (Polonsky & Henry 2016). Identifying novel therapeutic agents may benefit the large number of patients suffering from

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