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.

Ursolic Acid Lactone Obtained from Eucalyptus tereticornis Increases Glucose Uptake and Reduces Inflammatory Activity and Intracellular Neutral Fat: An In Vitro Study.

Obesity has a strong relationship to insulin resistance and diabetes mellitus, a chronic metabolic disease that alters many physiological functions. Naturally derived drugs have aroused great interest in treating obesity, and triterpenoids are natural compounds with multiple biological activities and antidiabetic mechanisms. Here, we evaluated the bioactivity of ursolic acid lactone (UAL), a lesser-known triterpenoid, obtained from Eucalyptus tereticornis. We used different cell lines to show for the first time that this molecule exhibits anti-inflammatory properties in a macrophage model, increases glucose uptake in insulin-resistant muscle cells, and reduces triglyceride content in hepatocytes and adipocytes. In 3T3-L1 adipocytes, UAL inhibited the expression of genes involved in adipogenesis and lipogenesis, enhanced the expression of genes involved in fat oxidation, and increased AMP-activated protein kinase phosphorylation. The range of biological activities demonstrated in vitro indicates that UAL is a promising molecule for fighting diabetes.

Bone remodeling: A tissue-level process emerging from cell-level molecular algorithms.

The human skeleton undergoes constant remodeling throughout the lifetime. Processes occurring on microscopic and molecular scales degrade bone and replace it with new, fully functional tissue. Multiple bone remodeling events occur simultaneously, continuously and independently throughout the body, so that the entire skeleton is completely renewed about every ten years.Bone remodeling is performed by groups of cells called Bone Multicellular Units (BMU). BMUs consist of different cell types, some specialized in the resorption of old bone, others encharged with producing new bone to replace the former. These processes are tightly regulated so that the amount of new bone produced is in perfect equilibrium with that of old bone removed, thus maintaining bone microscopic structure.To date, many regulatory molecules involved in bone remodeling have been identified, but the precise mechanism of BMU operation remains to be fully elucidated. Given the complexity of the signaling pathways already known, one may question whether such complexity is an inherent requirement of the process or whether some subset of the multiple constituents could fulfill the essential role, leaving functional redundancy to serve an alternative safety role. We propose in this work a minimal model of BMU function that involves a limited number of signals able to account for fully functional BMU operation. Our main assumptions were i) at any given time, any cell within a BMU can select only one among a limited choice of decisions, i.e. divide, die, migrate or differentiate, ii) this decision is irreversibly determined by depletion of an appropriate internal inhibitor and iii) the dynamics of any such inhibitor are coupled to that of specific external mediators, such as hormones, cytokines, growth factors. It was thus shown that efficient BMU operation manifests as an emergent process, which results from the individual and collective decisions taken by cells within the BMU unit in the absence of any external planning.

Effects of a Humor Therapy Program on Stress Levels in Pediatric Inpatients.

OBJECTIVE: Disease and hospitalization generate stress, which can affect the response to treatment. Humor has been used in many hospitals to decrease stress. The aim of this study was to evaluate the impact of a humor therapy program on stress levels in pediatric inpatients. METHODS: In the first phase, an intervention and a control group were studied over 2 consecutive 3-month periods; the interventions were performed by a team of artists trained in humor therapy. Salivary cortisol levels were measured by enzyme-linked immunosorbent assay, and the Weisz test, a pictorial chart that determines subjective stress perception, and the Parker test, which assesses objective stress, were applied. In the second phase, salivary cortisol levels were measured and the Weisz test was administered before and after the interventions. RESULTS: A total of 306 patients were recruited into this study: 198 in the first phase (94 in the intervention group and 104 in the nonintervention group) and 108 in the second phase. There were no differences between groups regarding age, sex, or medical diagnosis. The children in the intervention group presented lower cortisol levels, lower scores on the Parker test, and higher scores on the Weisz test than children in the nonintervention group. In the second phase, the children showed lower salivary cortisol levels and higher scores on the Weisz test after the intervention. CONCLUSIONS: Humor therapy has beneficial effects on stress and cortisol levels in pediatric inpatients. This supports the implementation and reinforcement of these therapies in pediatric hospitals.

Lathyrane Diterpenes from the Latex of Euphorbia laurifolia.

Two new macrocyclic diterpenes, 2-epi-latazienone (4) and 15ß-acetoxy-7ß-nicotinoyloxy-3ß,8α-di-(2-methylpropanoyloxy)-4αH,9αH,l1αH-lathyra- 5E,12E-dien-14-one (5), and three known lathyrane-type diterpenes (1-3) were isolated from Euphorbia laurifolia latex. Their structures were determined on the basis of a detailed analysis of their 1D and 2D NMR spectroscopic and mass spectral data.