Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome

• DOI: 10.1016/j.phrs.2025.107607
• Publication Date: 2025-01-16T00:19:18Z
• Authors: Sara E.L. Tolouei; Rodrigo Marcon; Fabiana Cardoso V...; Cristina Setim Fr...; Melina Heller; Edineia Lemos de ...; Sergio José Maced...; Adara Áurea dos S...; Ruth Fernandes Rocha; Guilherme Pasetto...; Naiani Ferreira M...; Jarbas Mota Sique...; João B. Calixto
• Keywords: High-fat diet; Metabolic dysfunction; Type 2 diabetes mellitus; Obesity; Therapeutics. Pharmacology; RM1-950; Nonalcoholic steatohepatitis; Ilex paraguariensis extract

Obesity is a global epidemic often associated with serious medical complications such as diabetes, hypertension and metabolic dysfunction-associated steatohepatitis. Considering the multifactorial nature of these diseases, medicinal plants could be valuable therapeutic strategy their phytoconstituents interact multiple relevant biological targets. In this context, Ilex paraguariensis emerges potential alternative to treat obesity diseases since several studies have demonstrated its anti-inflammatory, anti-obesity anti-diabetic effects. We present comprehensive complete non-clinical investigation efficacy, safety putative mechanisms action standardized aqueous extract I. (TI-076). also describe scalable preparation TI-076 demonstrate long-term stability. exhibits stability major constituents are well absorbed orally in mice rats. The five vivo proofs concept revealed that reduced obesity, hyperglycaemia, blood pressure, liver fat accumulation, levels serum insulin, leptin cholesterol, food intake, inflammation increased GLP-1 levels. through which acts seem involve modulation genes (Il1b, Nlrp3, Pparα Pparγ), white adipose metabolism (Cartpt, Mgll, Ramp3, Faah, Cck, Clps, damage fibrosis (Creb1, Col1a1 Col3a1). Finally, did not CYP3A4 proved safe. These findings strongly suggest holds great for clinical trials aimed at developing safe phytomedicine treating related diseases.