Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts

The <i>Cucurbita</i> genus comprises various species that are globally consumed and that are commonly used for their nutritional value but also for medicinal applications. Within the <i>Cucurbita</i> genus can be found <i>Cucurbita ficifolia</i> Bouché, a species...

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Main Authors: Tiago E. Coutinho, Carlos Martins-Gomes, Liliana Machado-Carvalho, Fernando M. Nunes, Amélia M. Silva
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/3/557
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author Tiago E. Coutinho
Carlos Martins-Gomes
Liliana Machado-Carvalho
Fernando M. Nunes
Amélia M. Silva
author_facet Tiago E. Coutinho
Carlos Martins-Gomes
Liliana Machado-Carvalho
Fernando M. Nunes
Amélia M. Silva
author_sort Tiago E. Coutinho
collection DOAJ
description The <i>Cucurbita</i> genus comprises various species that are globally consumed and that are commonly used for their nutritional value but also for medicinal applications. Within the <i>Cucurbita</i> genus can be found <i>Cucurbita ficifolia</i> Bouché, a species that is understudied regarding its potential value for the food industry, as a functional food, and for the pharmaceutical industry, as a source of nutraceuticals. Therefore, in this study we investigated the phytochemical composition and bioactivities of aqueous (AF) and methanolic (MF) fractions of <i>C. ficifolia</i> pulp and peel hydroethanolic (HE) extracts. HPLC-DAD-MS<sup>n</sup> and HPAEC-PAD analyses of extracts’ fractions revealed a low content of polyphenols and a significant content of sugars. Through in vitro inhibition assays of the enzymes alpha-amylase, acetylcholinesterase (AChE), and elastase, all fractions showed, respectively, antidiabetic, neuroprotective, and anti-aging activities. The safety profile and anti-tumoral activities were evaluated in various cell models (Caco-2, HaCaT, HepG2, and RAW 264.7), and results showed that the fractions obtained from pulp extract induce no/low cytotoxicity, while the methanolic fraction of peel induced cytotoxicity in all cell lines. At non-cytotoxic concentrations, aqueous and methanolic fractions of both extracts significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, revealing anti-inflammatory activity. Flow cytometry analysis showed that both aqueous fractions increased basal levels of glutathione (GSH) in Caco-2 cells, while not inducing oxidative stress, revealing potential as antioxidant dietary agents. However, the MF of peel HE extract induced oxidative stress in Caco-2 cells, as it increased reactive oxygen species (ROS) and lipid peroxidation. AF fraction of peel extract induced cell cycle arrest in the G0/G1 phase, while the other fractions induced cell cycle arrest in the S phase. In conclusion, <i>Cucurbita ficifolia</i> fruit presents potential as a functional food but also as a potential source of nutraceuticals, and peel waste products can be valorized by pharmaceutical and cosmeceutical industries as sources of bioactive molecules.
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spelling doaj-art-d0e53d6004f846a1a2ad882e8f6dac782025-08-20T03:12:35ZengMDPI AGMolecules1420-30492025-01-0130355710.3390/molecules30030557Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel ExtractsTiago E. Coutinho0Carlos Martins-Gomes1Liliana Machado-Carvalho2Fernando M. Nunes3Amélia M. Silva4Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, PortugalCentre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, PortugalCentre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, PortugalChemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, PortugalCentre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Trás-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, PortugalThe <i>Cucurbita</i> genus comprises various species that are globally consumed and that are commonly used for their nutritional value but also for medicinal applications. Within the <i>Cucurbita</i> genus can be found <i>Cucurbita ficifolia</i> Bouché, a species that is understudied regarding its potential value for the food industry, as a functional food, and for the pharmaceutical industry, as a source of nutraceuticals. Therefore, in this study we investigated the phytochemical composition and bioactivities of aqueous (AF) and methanolic (MF) fractions of <i>C. ficifolia</i> pulp and peel hydroethanolic (HE) extracts. HPLC-DAD-MS<sup>n</sup> and HPAEC-PAD analyses of extracts’ fractions revealed a low content of polyphenols and a significant content of sugars. Through in vitro inhibition assays of the enzymes alpha-amylase, acetylcholinesterase (AChE), and elastase, all fractions showed, respectively, antidiabetic, neuroprotective, and anti-aging activities. The safety profile and anti-tumoral activities were evaluated in various cell models (Caco-2, HaCaT, HepG2, and RAW 264.7), and results showed that the fractions obtained from pulp extract induce no/low cytotoxicity, while the methanolic fraction of peel induced cytotoxicity in all cell lines. At non-cytotoxic concentrations, aqueous and methanolic fractions of both extracts significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, revealing anti-inflammatory activity. Flow cytometry analysis showed that both aqueous fractions increased basal levels of glutathione (GSH) in Caco-2 cells, while not inducing oxidative stress, revealing potential as antioxidant dietary agents. However, the MF of peel HE extract induced oxidative stress in Caco-2 cells, as it increased reactive oxygen species (ROS) and lipid peroxidation. AF fraction of peel extract induced cell cycle arrest in the G0/G1 phase, while the other fractions induced cell cycle arrest in the S phase. In conclusion, <i>Cucurbita ficifolia</i> fruit presents potential as a functional food but also as a potential source of nutraceuticals, and peel waste products can be valorized by pharmaceutical and cosmeceutical industries as sources of bioactive molecules.https://www.mdpi.com/1420-3049/30/3/557<i>Cucurbita ficifolia</i> Bouchéantioxidantanti-inflammatoryneuroprotectoranti-agingcell cycle arrest
spellingShingle Tiago E. Coutinho
Carlos Martins-Gomes
Liliana Machado-Carvalho
Fernando M. Nunes
Amélia M. Silva
Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
Molecules
<i>Cucurbita ficifolia</i> Bouché
antioxidant
anti-inflammatory
neuroprotector
anti-aging
cell cycle arrest
title Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
title_full Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
title_fullStr Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
title_full_unstemmed Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
title_short Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from <i>Cucurbita ficifolia</i> Bouché Fruit Pulp and Peel Extracts
title_sort anti inflammatory anti hyperglycemic and anti aging activities of aqueous and methanolic fractions obtained from i cucurbita ficifolia i bouche fruit pulp and peel extracts
topic <i>Cucurbita ficifolia</i> Bouché
antioxidant
anti-inflammatory
neuroprotector
anti-aging
cell cycle arrest
url https://www.mdpi.com/1420-3049/30/3/557
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