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Transient Expression in Nicotiana Benthamiana Leaves for Triterpene Production at a Preparative Scale
Published on: August 16, 2018
Major triterpenoids from Eucalyptus tereticornis have enhanced beneficial effects in cellular models when mixed with
Laura I Betancur1, Diana L Muñoz2, Alis Guillen1
1GENMOL Group/Sede de Investigación Universitaria, Cl. 62 #52-59, University of Antioquia, 050010 Medellín, Antioquia, Colombia.
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.
Insights
A natural Eucalyptus extract (OBE100) effectively combats obesity-related inflammation and insulin resistance. This extract outperformed synthesized triterpenoid mixtures, showing greater efficacy and fewer side effects.
Area of Science:
- Pharmacology
- Natural Product Chemistry
- Metabolic Diseases
Background:
- Obesity is a primary risk factor for type 2 diabetes mellitus, driven by adipose tissue expansion and chronic inflammation, leading to insulin resistance.
- Current obesity treatments often cause adverse effects, necessitating the development of safer, more effective alternatives.
- A natural extract from Eucalyptus tereticornis (OBE100) previously showed anti-inflammatory, hypoglycemic, and hypolipidemic properties.
Purpose of the Study:
- To compare the biological effects of the natural extract OBE100 with reconstituted mixtures of its major triterpenoid compounds.
- To evaluate the efficacy and safety of OBE100 and triterpenoid mixtures in cellular models relevant to metabolic dysfunction.
Main Methods:
- Utilized various cell lines to assess cytotoxicity, reactive oxygen species (ROS) production, and inflammatory cytokine expression.
- Investigated the impact on glucose uptake, leptin and adiponectin expression, and lipid accumulation.
- Compared the effects of OBE100 against five different reconstituted mixtures of its primary triterpenoids (ursolic acid, oleanolic acid, ursolic acid lactone).
Main Results:
- OBE100 demonstrated superior efficacy compared to all formulated triterpenoid mixtures.
- OBE100 exhibited lower toxicity and a significant reduction in reactive oxygen species production.
- None of the reconstituted triterpenoid mixtures showed improved biological effects over OBE100.
Conclusions:
- The natural extract OBE100 is a highly effective agent for addressing cellular mechanisms underlying obesity and insulin resistance.
- Minor secondary metabolites within the natural extract likely enhance the beneficial properties of triterpenoids, particularly anti-inflammatory effects.
- OBE100 represents a promising therapeutic candidate with improved efficacy and safety profile compared to isolated triterpenoids.

