Avaliação da composição química e do perfil toxicológico e farmacológico dos extratos obtidos do resíduo industrial dos frutos de Passiflora edulis f. flavicarpa O. Deg
Hypertension and Diabetes Mellitus are diseases on the rise in the world and can cause several cardiovascular complications. Several drugs have efficacy in the treatment of these diseases, however, many have adverse effects and limitations of efficacy. The peel of the fruit of P. edulis f. flavic...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/31014 |
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| Resumo: | Hypertension and Diabetes Mellitus are diseases on the rise in the world and can cause several
cardiovascular complications. Several drugs have efficacy in the treatment of these diseases,
however, many have adverse effects and limitations of efficacy. The peel of the fruit of P. edulis
f. flavicarpa O. Degener (yellow passion fruit), considered a waste from the food industry, is
rich in bioactive compounds. Thus, due to the need to search for new treatments for
hypertension and diabetes, and in order to stimulate the development of herbal medicines with
species native to Brazil, the study aimed to evaluate the phytochemical composition, the toxicity
profile and the pharmacological potential of P. edulis peel extracts in non-clinical models of
hypertension and diabetes. Methodology was divided into the following parts: i: phytochemical
study, assessment of antioxidant activity in vitro and acute oral toxicity ii: non-clinical
assessment of antihypertensive activity in an ex vivo model of isolated arteries and in chronic
model of spontaneously hypertensive rats; iii acute and chronic non-clinical evaluation of
antidiabetic activity in models of type 1 diabetes, induced by streptozotocin. Two extracts were
produced (aqueous, prepared by decoction-AFA and hydroethanolic -AFM, obtained by
maceration) from the peel flour (dry and crushed peel) of P. edulis. Phytochemical analysis was
performerd by CCD, UHPLC/UV-DAD and HPLC-ESI-MSn. In both extracts C-glycosylated
flavonoids were identified. Among the identified flavonoids, it was possible to quantify the
content of vicenin-2, orientin, isoorientin, vitexin and isovitexin by HPLC-QqQ-MS/MS. The
polysaccharide pectin was found only in the AFA extract, through high performance steric
exclusion chromatography and NMR, its content was 34.3%. According to the results obtained
in acute oral toxicity, extracts were classified in category 5 by GSH (Globally Harmonized
Classification System for Chemical Substances and Mixtures) with LD50> 2000mg/kg, since
they did not show signs of acute toxicity. The in vitro antioxidant assay showed that the extracts
have good antioxidant activity observed by TAC, reducing power and DPPH tests. In the
evaluation of the antihypertensive effect, it was verified in an ex vivo model of isolated artery
that the AFM extract had the best relaxation profile, when compared to AFA. It effect may be
due to the opening of the potassium channels. In addition, the AFM extract at doses 200 and
400 mg/kg, orally, showed a significant hypotensive effect after 28 days of treatment and
improved vascular function in the mesenteric artery. This was verified by a decrease in vascular
hypercontractility and an increase in the vasorelaxant effect in response to sodium nitroprusside
and acetylcholine. There was also a decrease in endothelial dysfunction that can be attributed
to the increased bioavailability of nitric oxide. Thus, our hypothesis is that all these effects were
able to contribute to the reduction of peripheral vascular resistance, causing a significant
hypotensive effect. These results are unprecedented for the pericarp of P. edulis. In addition,
there was a decrease in plasma MDA levels in the heart and an increase in glutathione,
suggesting a decrease in oxidative stress, as well as an increase in plasma of anti-inflammatory
cytokines such as IL-10. In the acute in vivo antidiabetic model, it was observed that the extracts
at doses of 400 and 600 mg/kg associated with insulin were able to significantly reduce blood
glucose, when compared to diabetic rats that received only insulin, being this effect more
significant with AFA treatment. In the chronic antidiabetic model, the treatment with the
extracts during 60 days caused a significant reduction in glycemia observed at a dose of 400
mg/kg. In addition, extracts decreased MDA in the liver and MPO in the heart and kidney,
suggesting that the extracts may act by reducing oxidative stress and inflammation caused in
diabetes. Renal fibrosis was also reduced with chronic treatment. Taken together, toxicological
and pharmacological studies proved the safe and the potential effect of P.edulis peel fruit
extracts in development new phytoterapics. |
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