Major triterpenoids from Eucalyptus tereticornis have enhanced beneficial effects in cellular models when mixed with minor compounds present in raw extract

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 infl ammation 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-infl ammatory, hypoglycemic and hypolipidemic activities. The major compounds identifi ed 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 fi ve different reconstituted mixtures of these triterpenoids. Different cell lines were used to evaluate cytotoxicity, reactive oxygen species production, infl ammatory cytokine expression, glucose uptake induction, leptin and adiponectin expression, and lipid accumulation. OBE100 treatment was the most effi cacious and none of the formulated triterpenoid mixtures signifi cantly improved on this. Moreover, OBE100 was less toxic and reduced reactive oxygen species production. Our study showed that the proven benefi cial properties of triterpenoids may be enhanced due to the interaction with minor secondary metabolites present in the natural extract improving their anti-infl ammatory properties.

RNA-seq analysis reveals modulation of inflammatory pathways by an enriched-triterpene natural extract in mouse and human macrophage cell lines

“…The immunomodulatory effect of the OBE100 extract on macrophages has been reported [ 11 ], but the molecules underlying this effect are not yet fully understood. It is unclear whether the main effect is due to the mixture of triterpenes (UA, UAL, and OA), the uncharacterised fraction in the OBE100 extract, or both.…”

“…A specimen was deposited in the Herbarium of the University of Antioquia (# 178511). OBE100 was extracted as previously described [ 11 ]. Briefly, the dried leaves of Eu were extracted by a liquid-liquid separation with hexane: methanol: water 4:3:1 (v/v).…”

“…The recruitment, accumulation, and activation of pro-inflammatory macrophages in hypertrophic adipose tissue leads to the increase of production of pro-inflammatory adipokines such as TNF-α and IL-6 that is shown to induce insulin resistance in different tissues [ [6] , [7] , [8] , [9] ].For this reason, new therapeutic options for managing diabetes mellitus and its complications target inflammation. An extract from Eu leaves, named OBE100, possesses hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory activities [ [10] , [11] , [12] , [13] ]. OBE100 contains three pentacyclic triterpenoids as main molecules: 47.6 % ursolic acid (UA), 14.1 % oleanolic acid (OA), and 16.3 % ursolic acid lactone (UAL) [ 11 ].…”

“…An extract from Eu leaves, named OBE100, possesses hypoglycemic, hypolipidemic, antioxidant and anti-inflammatory activities [ [10] , [11] , [12] , [13] ]. OBE100 contains three pentacyclic triterpenoids as main molecules: 47.6 % ursolic acid (UA), 14.1 % oleanolic acid (OA), and 16.3 % ursolic acid lactone (UAL) [ 11 ]. Triterpenoids are biomolecules composed of six isoprene units, and the most common and widely distributed are the pentacyclic triterpenoids [ 14 ].…”

“…We have previously shown that OBE100 significantly decreases the expression of IL-6, TNFα, IL-1β and MCP-1 in both mouse and human macrophages [ 12 ] and confirmed that this Eu extract improves the inflammation process caused by a high-fat diet reducing the expression of proinflammatory cytokines, such as MCP-1, TNF- α , IL-1, and IL-6 in mice adipose tissue [ 13 ]. Interestingly, UA, OA, and UAL mixed with unknown minor metabolites in OBE100 extract present superior anti-inflammatory, hypoglycemic, and hypolipidemic effects than reconstituted triterpenoid mixtures [ 11 ]. Transcriptome sequencing (RNA-Seq) is a high-sensitivity technique that can be used to characterise the changes in gene expression and identify novel transcriptome features and cell culture is an essential technique to expand molecular knowledge.…”