Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome
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 a valuable therapeutic strategy as their phytoconst...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Pharmacological Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661825000325 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832573196779388928 |
|---|---|
| author | Sara E.L. Tolouei Rodrigo Marcon Fabiana Cardoso Vilela Cristina Setim Freitas Melina Heller Edineia Lemos de Andrade Sergio José Macedo Júnior Adara Áurea dos Santos Ruth Fernandes Rocha Guilherme Pasetto Fadanni Naiani Ferreira Marques Jarbas Mota Siqueira Júnior João B. Calixto |
| author_facet | Sara E.L. Tolouei Rodrigo Marcon Fabiana Cardoso Vilela Cristina Setim Freitas Melina Heller Edineia Lemos de Andrade Sergio José Macedo Júnior Adara Áurea dos Santos Ruth Fernandes Rocha Guilherme Pasetto Fadanni Naiani Ferreira Marques Jarbas Mota Siqueira Júnior João B. Calixto |
| author_sort | Sara E.L. Tolouei |
| collection | DOAJ |
| description | 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 a valuable therapeutic strategy as their phytoconstituents interact with multiple and relevant biological targets. In this context, Ilex paraguariensis emerges as a potential alternative to treat obesity and associated metabolic diseases since several studies have demonstrated its anti-inflammatory, anti-obesity and anti-diabetic effects. We present a comprehensive and complete non-clinical investigation of the efficacy, safety and putative mechanisms of action of a standardized aqueous extract of I. paraguariensis (TI-076). We also describe a scalable preparation of TI-076 and demonstrate its long-term stability. TI-076 exhibits long-term stability and its major constituents are well absorbed orally in mice and rats. The five in vivo proofs of concept studies revealed that TI-076 reduced obesity, hyperglycaemia, blood pressure, liver fat accumulation, levels of serum insulin, leptin and cholesterol, food intake, inflammation and increased GLP-1 levels. The mechanisms through which TI-076 acts seem to involve the modulation of several genes associated with inflammation (Il1b, Nlrp3, Pparα and Pparγ), white adipose and liver metabolism (Cartpt, Mgll, Ramp3, Faah, Cck, Clps, Pparα and Pparγ), liver damage and fibrosis (Creb1, Col1a1 and Col3a1). Finally, TI-076 did not interact with CYP3A4 in vivo and proved to be safe. These findings strongly suggest that TI-076 holds great potential for clinical trials aimed at developing a safe phytomedicine for treating obesity and related metabolic diseases. |
| format | Article |
| id | doaj-art-1df2746bb17148a8954d5a083ca9b01b |
| institution | Kabale University |
| issn | 1096-1186 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj-art-1df2746bb17148a8954d5a083ca9b01b2025-02-02T05:26:50ZengElsevierPharmacological Research1096-11862025-03-01213107607Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndromeSara E.L. Tolouei0Rodrigo Marcon1Fabiana Cardoso Vilela2Cristina Setim Freitas3Melina Heller4Edineia Lemos de Andrade5Sergio José Macedo Júnior6Adara Áurea dos Santos7Ruth Fernandes Rocha8Guilherme Pasetto Fadanni9Naiani Ferreira Marques10Jarbas Mota Siqueira Júnior11João B. Calixto12Centro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCentro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilCorresponding author.; Centro de Inovação e Ensaios Pré-Clínicos. Avenida Luiz Boiteux Piazza, 1302 Cachoeira do Bom Jesus, Florianópolis, Santa Catarina 88056-000, BrazilObesity 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 a valuable therapeutic strategy as their phytoconstituents interact with multiple and relevant biological targets. In this context, Ilex paraguariensis emerges as a potential alternative to treat obesity and associated metabolic diseases since several studies have demonstrated its anti-inflammatory, anti-obesity and anti-diabetic effects. We present a comprehensive and complete non-clinical investigation of the efficacy, safety and putative mechanisms of action of a standardized aqueous extract of I. paraguariensis (TI-076). We also describe a scalable preparation of TI-076 and demonstrate its long-term stability. TI-076 exhibits long-term stability and its major constituents are well absorbed orally in mice and rats. The five in vivo proofs of concept studies revealed that TI-076 reduced obesity, hyperglycaemia, blood pressure, liver fat accumulation, levels of serum insulin, leptin and cholesterol, food intake, inflammation and increased GLP-1 levels. The mechanisms through which TI-076 acts seem to involve the modulation of several genes associated with inflammation (Il1b, Nlrp3, Pparα and Pparγ), white adipose and liver metabolism (Cartpt, Mgll, Ramp3, Faah, Cck, Clps, Pparα and Pparγ), liver damage and fibrosis (Creb1, Col1a1 and Col3a1). Finally, TI-076 did not interact with CYP3A4 in vivo and proved to be safe. These findings strongly suggest that TI-076 holds great potential for clinical trials aimed at developing a safe phytomedicine for treating obesity and related metabolic diseases.http://www.sciencedirect.com/science/article/pii/S1043661825000325Ilex paraguariensis extractObesityHigh-fat dietType 2 diabetes mellitusNonalcoholic steatohepatitisMetabolic dysfunction |
| spellingShingle | Sara E.L. Tolouei Rodrigo Marcon Fabiana Cardoso Vilela Cristina Setim Freitas Melina Heller Edineia Lemos de Andrade Sergio José Macedo Júnior Adara Áurea dos Santos Ruth Fernandes Rocha Guilherme Pasetto Fadanni Naiani Ferreira Marques Jarbas Mota Siqueira Júnior João B. Calixto Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome Pharmacological Research Ilex paraguariensis extract Obesity High-fat diet Type 2 diabetes mellitus Nonalcoholic steatohepatitis Metabolic dysfunction |
| title | Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome |
| title_full | Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome |
| title_fullStr | Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome |
| title_full_unstemmed | Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome |
| title_short | Preclinical development of a standardized extract of Ilex paraguariensis A.St.-Hil for the treatment of obesity and metabolic syndrome |
| title_sort | preclinical development of a standardized extract of ilex paraguariensis a st hil for the treatment of obesity and metabolic syndrome |
| topic | Ilex paraguariensis extract Obesity High-fat diet Type 2 diabetes mellitus Nonalcoholic steatohepatitis Metabolic dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S1043661825000325 |
| work_keys_str_mv | AT saraeltolouei preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT rodrigomarcon preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT fabianacardosovilela preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT cristinasetimfreitas preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT melinaheller preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT edineialemosdeandrade preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT sergiojosemacedojunior preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT adaraaureadossantos preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT ruthfernandesrocha preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT guilhermepasettofadanni preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT naianiferreiramarques preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT jarbasmotasiqueirajunior preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome AT joaobcalixto preclinicaldevelopmentofastandardizedextractofilexparaguariensisasthilforthetreatmentofobesityandmetabolicsyndrome |