{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T21:33:28Z","timestamp":1772832808686,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"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 (FCT)","doi-asserted-by":"publisher","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation (FCT)","doi-asserted-by":"publisher","award":["PB\/DB\/135330\/2017"],"award-info":[{"award-number":["PB\/DB\/135330\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Portuguese Science and Technology Foundation (FCT)","doi-asserted-by":"publisher","award":["CENTRO-01-0247-FEDER-033815"],"award-info":[{"award-number":["CENTRO-01-0247-FEDER-033815"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Project InovEP","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"Project InovEP","award":["PB\/DB\/135330\/2017"],"award-info":[{"award-number":["PB\/DB\/135330\/2017"]}]},{"name":"Project InovEP","award":["CENTRO-01-0247-FEDER-033815"],"award-info":[{"award-number":["CENTRO-01-0247-FEDER-033815"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Labdanum resin or \u201cgum\u201d can be obtained from Cistus ladanifer L. by two different extraction methods: the Zamorean and the Andalusian processes. Although its main use is in the fragrance and perfumery sectors, ethnobotanical reports describe its use for medicinal purposes in managing hyperglycemia and mental illnesses. However, data concerning the bioactivities and pharmacological applications are scarce. In this work, it was found that the yield of labdanum resin extracted by the Andalusian process was 25-fold higher than the Zamorean one. Both resins were purified as absolutes, and the Andalusian absolute was purified into diterpenoid and flavonoid fractions. GC-EI-MS analysis confirmed the presence of phenylpropanoids, labdane-type diterpenoids, and methylated flavonoids, which are already described in the literature, but revealed other compounds, and showed that the different extracts presented distinct chemical profile. The potential antidiabetic activity, by inhibition of \u03b1-amylase and \u03b1-glucosidase, and the potential neuroprotective activity, by inhibition of acetylcholinesterase, were investigated. Diterpenoid fraction produced the higher \u03b1-amylase inhibitory effect (~30% and ~40% at 0.5 and 1 mg\/mL, respectively). Zamorean absolute showed the highest \u03b1-glucosidase inhibitory effect (~14% and ~24%, at 0.5 and 1 mg\/mL, respectively). Andalusian absolute showed the highest acetylcholinesterase inhibitory effect (~70% and ~75%, at 0.5 and 1 mg\/mL, respectively). Using Caco-2 and HepG2 cell lines, Andalusian absolute and its purified fractions showed moderate cytotoxic\/anti-proliferative activity at 24 h exposure (IC50 = 45\u201370 \u00b5g\/mL, for Caco-2; IC50 = 60\u201380 \u00b5g\/mL, for HepG2), whereas Zamorean absolute did not produce cytotoxicity (IC50 \u2265 200.00 \u00b5g\/mL). Here we show, for the first time, that labdanum resin obtained by the Andalusian process, and its fractions, are composed of phytochemicals with anti-diabetic, neuroprotective and anti-proliferative potential, which are worth investigating for the pharmaceutical industry. However, toxic side-effects must also be addressed when using these products by ingestion, as done traditionally.<\/jats:p>","DOI":"10.3390\/molecules29102222","type":"journal-article","created":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T10:31:16Z","timestamp":1715250676000},"page":"2222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Labdanum Resin from Cistus ladanifer L. as a Source of Compounds with Anti-Diabetic, Neuroprotective and Anti-Proliferative Activity"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5017-6117","authenticated-orcid":false,"given":"David F.","family":"Fraz\u00e3o","sequence":"first","affiliation":[{"name":"Center for Research and Technology of Agro-Environmental and Biological Sciences (CITAB-UTAD), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal"},{"name":"Plant Biotechnology Center of Beira Interior (CBPBI), Quinta da Senhora de M\u00e9rcules, Apartado 119, 6001-909 Castelo Branco, Portugal"},{"name":"Mediterranean Institute for Agriculture, Environment and Development (MED), Centre of Agronomic and Agro-Industrial Biotechnology of Alentejo (CEBAL), 7801-908 Beja, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-3661","authenticated-orcid":false,"given":"Carlos","family":"Martins-Gomes","sequence":"additional","affiliation":[{"name":"Center for Research and Technology of Agro-Environmental and Biological Sciences (CITAB-UTAD), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-3770","authenticated-orcid":false,"given":"Teresa Sosa","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Plant Biology, Ecology and Earth Sciences, Faculty of Science, University of Extremadura, 06006 Badajoz, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1238-9386","authenticated-orcid":false,"given":"Fernanda","family":"Delgado","sequence":"additional","affiliation":[{"name":"Plant Biotechnology Center of Beira Interior (CBPBI), Quinta da Senhora de M\u00e9rcules, Apartado 119, 6001-909 Castelo Branco, Portugal"},{"name":"Research Centre for Natural Resources, Environment and Society (CERNAS), Polytechnic Institute of Castelo Branco (IPCB), Quinta da Senhora de M\u00e9rcules, Apartado 119, 6001-909 Castelo Branco, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3387-4487","authenticated-orcid":false,"given":"Jos\u00e9 C.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Plant Biotechnology Center of Beira Interior (CBPBI), Quinta da Senhora de M\u00e9rcules, Apartado 119, 6001-909 Castelo Branco, Portugal"},{"name":"Research Centre for Natural Resources, Environment and Society (CERNAS), Polytechnic Institute of Castelo Branco (IPCB), Quinta da Senhora de M\u00e9rcules, Apartado 119, 6001-909 Castelo Branco, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Center for Research and Technology of Agro-Environmental and Biological Sciences (CITAB-UTAD), University of Tr\u00e1s-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 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), Quinta de Prados, 5001-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Carta da tipologia florestal de Portugal Continental","volume":"13","author":"Azevedo","year":"2005","journal-title":"Silva Lusit."},{"key":"ref_2","unstructured":"Castroviejo, S. 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