Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Online First

Angiotensin-(1-7) is a crucial endocrine modulatory peptide that can enhance conditions like diabetes, obesity, and other features of metabolic syndrome. However, there is a lack of data on its long-term effects.

This study aimed to assess the impact of chronic oral administration of Angiotensin-(1-7) on adipose tissue modulation and metabolic processes in mice.

The Angiotensin-(1-7) peptide oral formulation was encapsulated within the hydroxypropyl-β-cyclodextrin oligosaccharide (HPβCD) matrix. Male Swiss mice were divided into 4 groups: standard diet (ST)+HPßCD; ST+Ang-(1-7); high-fat diet HFD+HPßCD, and HFD+Ang-(1-7). The treatment lasted for 12 months, during which body weight, food intake, glycemic and lipid profiles, visceral adiposity, oxidative stress indicators, histological parameters, quantitative real-time PCR assessments, and comprehensive in silico bioinformatics analyses were conducted.

Prolonged treatment with Ang-(1-7) led to improvements in glucose levels, visceral body adiposity, decreased cholesterol and triglyceride levels, and reduced oxidative stress. Bioinformatics analysis revealed that AKT1, an insulin signaling effector (INS), and key inflammatory markers like IL-6 and VEGF may be potential molecular mediators of Angiotensin-(1-7) effects. Non-obese animals treated with Angiotensin-(1-7) showed increased expression levels of AKT1, supporting the findings from the bioinformatics analysis.

This study demonstrates that chronic oral use of Ang-(1-7) enhances adipose and metabolic parameters, suggesting its potential as a long-term therapeutic agent for regulating metabolic disorders.

Eleutherine bulbosa (Miller) Urb, popularly known as “marupazinho”, is frequently used in traditional medicine for treating various diseases, including hypertension, ulcers, constipation, and intestinal infection. However, there is little scientific knowledge available regarding the pharmacological effects of this species. Thus in vivo and in silico phytochemical studies are required to establish whether this plant has these effects. Further tests were necessary to evaluate the pharmacological activity of the compounds found in this plant, and demonstrate results related to the anti-inflammatory process, which will serve as the basis for future research in this area.

Therefore, our study aimed to determine the acute toxicity levels of the hexanoic fraction of the ethanolic extract of Eleutherine bulbosa (referred to as ExtHF) using adult zebrafish, with the determination of the LD50, behavioral and histopathological evaluations, as well as the anti-inflammatory potential of ExtHF, at different doses, in abdominal edema induced by carrageenan. The acute toxicity study and histopathological analysis in zebrafish showed that ExtHF has a high toxic potential, with an LD50 of 346.74 mg/kg. However, ExtHF showed an anti-inflammatory effect by inhibiting abdominal edema at all doses tested.

The inhibition rate of 66.2% and 62.4%, respectively, was observed with the 2.5 mg/kg dose, respectively, indicating that ExtHF is safe in terms of acute toxicity based on behavioral changes, mortality rate, and histopathological examination. Therefore, ExtHF has an acceptable level of safety for acute toxicity, defined by the analysis of behavioral changes, mortality, and histopathology, showing a significant anti-inflammatory effect in zebrafish at all doses, showing that ExtHF was very efficient in preventing the formation of edema, in addition, it was also revealed that ExtHF has a great effect in reversing the edema which is already installed.

Molecular docking studies revealed that the eleutherol molecule isolated from E. bulbosa has a dual inhibition profile against cyclooxygenase-1 and 2.