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

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.

Pentacyclic Triterpene Profile and Its Biosynthetic Pathway in Cecropia telenitida as a Prospective Dietary Supplement.

Promising research over the past decades has shown that some types of pentacyclic triterpenes (PTs) are associated with the prevention of type 2 diabetes (T2D), especially those found in foods. The most abundant edible sources of PTs are those belonging to the ursane and oleanane scaffold. The principal finding is that Cecropia telenitida contains abundant oleanane and ursane PT types with similar oxygenation patterns to those found in food matrices. We studied the compositional profile of a rich PT fraction (DE16-R) and carried out a viability test over different cell lines. The biosynthetic pathway connected to the isolated PTs in C. telenitida offers a specific medicinal benefit related to the modulation of T2D. This current study suggests that this plant can assemble isobaric, positional isomers or epimeric PT. Ursane or oleanane scaffolds with the same oxygenation pattern are always shared by the PTs in C. telenitida, as demonstrated by its biosynthetic pathway. Local communities have long used this plant in traditional medicine, and humans have consumed ursane and oleanane PTs in fruits since ancient times, two key points we believe useful in considering the medicinal benefits of C. telenitida and explaining how a group of molecules sharing a closely related scaffold can express effectiveness.

Triterpene-enriched fractions from Eucalyptus tereticornis ameliorate metabolic alterations in a mouse model of diet-induced obesity.

ETNOPHARMACOLOGICAL RELEVANCE: Eucalyptus tereticornis Sm. (Eu) is a plant species used in traditional medicine to treat diabetes mellitus. Eu leaf extracts have been shown to regulate immuno-metabolic activities that are associated with obesity and insulin resistance. OBE100 and OBE104 are two natural Eu extracts that are rich in pentacyclic triterpenes. The major compounds identified in OBE100 are ursolic acid (UA), oleanolic acid (OA), and ursolic acid lactone (UAL), and the major compounds identified in OBE104 are UA and OA. AIM OF THE STUDY: This study aimed to investigate the effects of two extracts from Eu leaves with different triterpene composition in a nutritional animal model of prediabetes. METHODS: A mouse model of diet-induced obesity was used to analyze the effects of the OBE100 and OBE104 treatments on metabolic markers and gene expression in liver and visceral adipose tissue. RESULTS: Treating the prediabetic mouse model with OBE100 and OBE104 increased glucose tolerance. However, only the Eu extract that contained three triterpenes reduced mouse body weight, hepatic and adipose fat content, and plasma lipid levels. OBE100 treatment also led to decreased hepatic mRNA levels of PPARA, CPT1A, and SERBP1. In visceral adipose tissue, OBE100 treatment reduced expression of PPARA and ACACA and increased UCP1 expression. CONCLUSIONS: These results suggest that developing a new multitargeting bioactive compound from the natural extract from Eu may help combat obesity and diabetes. Treatment with OBE100 had better effects than OBE104 in a diet-induced obesity mouse model, suggesting that the OBE100 extract, which contains three triterpenes, may be beneficial in combating obesity.

Metabolic Activity of Anthocyanin Extracts Loaded into Non-ionic Niosomes in Diet-Induced Obese Mice.

PURPOSE: Anthocyanins (ACNs) are polyphenols that might reduce pathological processes associated with type 2 diabetes mellitus and other chronic diseases, but their bioavailability is still controversial. In this study, the metabolic activity of oral delivery of ACN-loaded niosomes was investigated and evaluated in a diet-induced obesity (DIO) mice model. METHODS: ACNs extracted from Vaccinium Meridionale by the supercritical fluid extraction method were loaded in niosomes. The niosomal formulation was physically characterized and further administrated in drinking water to obese, insulin resistant mouse. We evaluated the effect of ACN loaded niosomes on hyperglycemia, glucose and insulin intolerance and insulin blood levels in C57BL/6 J mice fed with a high-fat diet. RESULTS: The ACN-loaded particles were moderately monodisperse, showed a negative surface charge and 57% encapsulation efficiency. The ACN-loaded niosomes ameliorated the insulin resistance and glucose intolerance in the DIO mice model. Additionally, they reduced animal weight and plasma insulin, glucose, leptin and total cholesterol levels in obese mice. CONCLUSION: ACN-loaded niosomes administration, as a functional drink, had a beneficial effect on the reversal of metabolic abnormalities associated with obesity.

Serjanic Acid Improves Immunometabolic Markers in a Diet-Induced Obesity Mouse Model.

Plant extracts from Cecropia genus have been used by Latin-American traditional medicine to treat metabolic disorders and diabetes. Previous reports have shown that roots of Cecropia telenitida that contains serjanic acid as one of the most prominent and representative pentacyclic triterpenes. The study aimed to isolate serjanic acid and evaluate its effect in a prediabetic murine model by oral administration. A semi-pilot scale extraction was established and serjanic acid purification was followed using direct MALDI-TOF analysis. A diet induced obesity mouse model was used to determine the impact of serjanic acid over selected immunometabolic markers. Mice treated with serjanic acid showed decreased levels of cholesterol and triacylglycerols, increased blood insulin levels, decreased fasting blood glucose and improved glucose tolerance, and insulin sensitivity. At transcriptional level, the reduction of inflammation markers related to adipocyte differentiation is reported.

Immunometabolic regulation by triterpenes of Eucalyptus tereticornis in adipose tissue cell line models.

BACKGROUND: Eucalyptus tereticornis Sm (Myrtaceae) is a plant used in traditional medicine to control obesity, insulin resistance and diabetes. Chronic adipose tissue inflammation is involved in generating insulin resistance, the greatest risk factor in developing type 2 diabetes mellitus and cardiovascular disease. In the present study, a mixture of triterpenes, as obtained from the starting plant material, was evaluated in inflamed adipose tissue cells models. AIM: Our goal is to advance into the understanding, at the cellular level, of the immunometabolic effects of the triterpene mixes from Eucalyptus tereticornis in in vitro models of mouse and human adipose tissues. METHODS: Triterpene mixes were obtained from Eucalyptus tereticornis leaves by organic extraction. The major compounds of these mixes were identified by 1H NMR and 13C NMR in addition to HPLC using primary and secondary standards of ursolic acid, oleanolic acid and ursolic acid lactone. To provide an approach for evaluating the cellular and molecular mechanisms through which triterpene mixes act to modify the metabolic processes associated with obesity, mouse macrophage and adipocyte cell lines, human macrophage cell line and primary culture of human adipocytes were used as models. RESULTS: Adipocytes treated with the two natural chemically characterized triterpene mixes partially reduce lipogenesis and leptin expression. Additionally, an increase in the transcriptional expression of PPARγ, and C/EBPα is observed. In macrophages, these triterpene mixes, decrease the transcriptional and translational expression of pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin 1ß (IL-1ß) and tumoral necrosis factor α (TNFα). Conditioned medium of 3T3-L1 adipocytes treated with the triterpene mix shows a stronger anti-inflammatory response on activated J774A.1 macrophages. CONCLUSION: The mixtures of the three triterpenes in the proportions obtained from the plant material may act on different components of the cell, generating a different response, which, in some cases, is more powerful than that seen when exposure to only two triterpenes. It makes this three triterpenes mix a good phytotherapeutic prototype for pathologies as complex as those associated with obesity.

Antihyperglycemic Activity of Eucalyptus tereticornis in Insulin-Resistant Cells and a Nutritional Model of Diabetic Mice.

Eucalyptus tereticornis is a plant used in traditional medicine to control diabetes, but this effect has not been proved scientifically. Here, we demonstrated through in vitro assays that E. tereticornis extracts increase glucose uptake and inhibit their production in insulin-resistant C2C12 and HepG2 cells, respectively. Furthermore, in a nutritional model using diabetic mice, the administration of ethyl acetate extract of E. tereticornis reduced fasting glycaemia, improved tolerance to glucose, and reduced resistance to insulin. Likewise, this extract had anti-inflammatory effects in adipose tissue when compared to control diabetic mice. Via bioguided assays and sequential purification of the crude extract, a triterpenoid-rich fraction from ethyl acetate extracts was shown to be responsible for the biological activity. Similarly, we identified the main compound responsible for the antihyperglycemic activity in this extract. This study shows that triterpenes found in E. tereticornis extracts act as hypoglycemic/antidiabetic compounds and contribute to the understanding of their use in traditional medicine.

Evaluation of the hypoglycemic effects of flavonoids and extracts from Jatropha gossypifolia L.

Jatropha gossypifolia L. (Euphorbiaceae) is a plant widely used in the treatment of type 2 diabetes mellitus (T2DM), but there are few scientific reports validating its activity in this area. In this work and through a bioguided assay, a crude extract stimulated glucose uptake in C2C12 myotubes up to 30%, thereby reducing insulin resistance induced by fatty acids compared to the basal control. A chromatographic fraction applied intraperitoneally (IP) in mice reduced glucose by 42% in a mouse model of T2DM, after administration of 10 doses during 20 days. A flavanone was purified from this active fraction and its structure was assigned by 1H- and 13C-NMR (1D and 2D) and MS. This compound retains the previously reported activity, stimulating in vitro the glucose uptake in a concentration-dependent manner. This study indicates that Jatropha gossypifolia L. extracts enhance glucose uptake in cultured myotubes and adipocytes and also improving glucose tolerance in an in vivo model.