Publicação
Influence of Guava Leaf Decoctions on Cholesterol Permeation through the Intestinal Barrier and Cholesterol Biosynthesis
| Resumo: | Psidium guajava L. leaf decoction has been used in traditional medicine due to its beneficial health effects, both in the prevention and treatment of diseases, namely hypercholesterolemia. This disorder consists of abnormally high levels of blood cholesterol and it’s a risk factor for the development of cardiovascular diseases. Cholesterol homeostasis is maintained through the endogenous synthesis, intestinal absorption, and hepatic excretion. The aim of this thesis was to evaluate the bioactivity and chemical composition of P. guajava leaf decoction and its influence on cholesterol absorption and metabolism. To do so, cholesterol permeation through the simulated intestinal barrier, inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and inhibition of cholesterol transporters was assessed under the decoction’s influence. The aqueous extract (PG1) and the ethanolic precipitation supernatant (PG2) and pellet (PG3) from P. guajava leaf decoction were studied. It was observed that PG1 and PG2 were rich in phenolic compounds, whereas PG3 had low concentration of these bioactive molecules. The samples also possess strong antioxidant power (EC50 7.5 ± 0.4, 11.9 ± 0.5, and 7.3 ± 0.6 µg/mL for PG1, PG2, and PG3, respectively) and acetylcholinesterase inhibitory activity was only achieved by PG1 and PG2 (48.66 ± 1.39 and 63.44 ± 1.13 µg/mL for PG1 and PG2, respectively). In addition, PG1 and PG2 weren’t cytotoxic. Some phenolic compounds from PG1 and PG2 were able to permeate the intestinal barrier, ranging from 0.07 to 9.95%. The decoction also decreased cholesterol absorption in the simulated intestinal wall (55% and 24% for PG1 and PG2, respectively). The decoction inhibited cholesterol biosynthesis by inhibiting the HMGR activity (IC50 8.4 ± 0.5 µg/mL for PG1) and decreased the expression of cholesterol transporters NPC1L1 (ranging from 16 to 94%), ABCG5 (ranging from 28 to 98%), and ABCG8 (ranging from 24 to 80%). Additionally, FTIR data suggested a decrease in protein expression related to modifications at the transcription level. In conclusion, P. guajava leaf decoction was reported to influence cholesterol homeostasis at several levels, which helps explain its use and effects in traditional medicine. |
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| Autores principais: | Lorena, Maria Constança Batista da Cunha e |
| Assunto: | Psidium guajava L. colesterol compostos fenólicos transportadores de colesterol Teses de mestrado - 2020 |
| Ano: | 2020 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Psidium guajava L. leaf decoction has been used in traditional medicine due to its beneficial health effects, both in the prevention and treatment of diseases, namely hypercholesterolemia. This disorder consists of abnormally high levels of blood cholesterol and it’s a risk factor for the development of cardiovascular diseases. Cholesterol homeostasis is maintained through the endogenous synthesis, intestinal absorption, and hepatic excretion. The aim of this thesis was to evaluate the bioactivity and chemical composition of P. guajava leaf decoction and its influence on cholesterol absorption and metabolism. To do so, cholesterol permeation through the simulated intestinal barrier, inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and inhibition of cholesterol transporters was assessed under the decoction’s influence. The aqueous extract (PG1) and the ethanolic precipitation supernatant (PG2) and pellet (PG3) from P. guajava leaf decoction were studied. It was observed that PG1 and PG2 were rich in phenolic compounds, whereas PG3 had low concentration of these bioactive molecules. The samples also possess strong antioxidant power (EC50 7.5 ± 0.4, 11.9 ± 0.5, and 7.3 ± 0.6 µg/mL for PG1, PG2, and PG3, respectively) and acetylcholinesterase inhibitory activity was only achieved by PG1 and PG2 (48.66 ± 1.39 and 63.44 ± 1.13 µg/mL for PG1 and PG2, respectively). In addition, PG1 and PG2 weren’t cytotoxic. Some phenolic compounds from PG1 and PG2 were able to permeate the intestinal barrier, ranging from 0.07 to 9.95%. The decoction also decreased cholesterol absorption in the simulated intestinal wall (55% and 24% for PG1 and PG2, respectively). The decoction inhibited cholesterol biosynthesis by inhibiting the HMGR activity (IC50 8.4 ± 0.5 µg/mL for PG1) and decreased the expression of cholesterol transporters NPC1L1 (ranging from 16 to 94%), ABCG5 (ranging from 28 to 98%), and ABCG8 (ranging from 24 to 80%). Additionally, FTIR data suggested a decrease in protein expression related to modifications at the transcription level. In conclusion, P. guajava leaf decoction was reported to influence cholesterol homeostasis at several levels, which helps explain its use and effects in traditional medicine. |
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