{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:15:34Z","timestamp":1774541734733,"version":"3.50.1"},"reference-count":71,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020 (CITAB; https:\/\/doi.org\/10.54499\/UIDB\/04033\/2020)"],"award-info":[{"award-number":["UIDB\/04033\/2020 (CITAB; https:\/\/doi.org\/10.54499\/UIDB\/04033\/2020)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","doi-asserted-by":"publisher","award":["UIDB\/00616\/2020 (CQVR; https:\/\/doi.org\/10.54499\/UIDP\/00616\/2020)"],"award-info":[{"award-number":["UIDB\/00616\/2020 (CQVR; https:\/\/doi.org\/10.54499\/UIDP\/00616\/2020)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","doi-asserted-by":"publisher","award":["LA\/P\/0126\/2020 (Inov4Agro)"],"award-info":[{"award-number":["LA\/P\/0126\/2020 (Inov4Agro)"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The Cucurbita genus comprises various species that are globally consumed and that are commonly used for their nutritional value but also for medicinal applications. Within the Cucurbita genus can be found Cucurbita ficifolia Bouch\u00e9, 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 C. ficifolia pulp and peel hydroethanolic (HE) extracts. HPLC-DAD-MSn and HPAEC-PAD analyses of extracts\u2019 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, Cucurbita ficifolia 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.<\/jats:p>","DOI":"10.3390\/molecules30030557","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T09:42:23Z","timestamp":1737970943000},"page":"557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Anti-Inflammatory, Anti-Hyperglycemic, and Anti-Aging Activities of Aqueous and Methanolic Fractions Obtained from Cucurbita ficifolia Bouch\u00e9 Fruit Pulp and Peel Extracts"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6533-6205","authenticated-orcid":false,"given":"Tiago E.","family":"Coutinho","sequence":"first","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-3661","authenticated-orcid":false,"given":"Carlos","family":"Martins-Gomes","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Chemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3230-4650","authenticated-orcid":false,"given":"Liliana","family":"Machado-Carvalho","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-318X","authenticated-orcid":false,"given":"Fernando M.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Chemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Department of Chemistry, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4gro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Nunes, F.M., and Silva, A.M. 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