{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:49:48Z","timestamp":1760057388386,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T00:00:00Z","timestamp":1739145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union","award":["POWR.03.02.00-00-I014\/17-0"],"award-info":[{"award-number":["POWR.03.02.00-00-I014\/17-0"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Salvia apiana Jepson is an endemic North American species characterized by a rich phytochemical profile including abietane-type diterpenoids, phenolic acids, flavonoids, and thujone-free essential oil (EO). The current study was aimed at increasing EO production in bioreactor-grown S. apiana microshoot culture through biotic elicitation using chitosan, ergosterol, and yeast extract (YE). Additionally, the immunomodulatory effects of the major volatile constituent of white sage\u20141,8-cineole\u2014as well as EOs obtained from both S. apiana microshoots and leaves of field-grown plants, were assessed. EOs were isolated via hydrodistillation and analyzed by GC\/MS and GC\/FID. Biological assays included flow cytometric evaluation of the proliferation and apoptosis rates of human CD4 and CD8 T lymphocytes, obtained from healthy volunteers and subjected to different concentrations of EOs and 1,8-cineole. Elicitation with 100 mg\/L YE improved the production of EO in S. apiana microshoots by 9.4% (1.20% v\/m). EOs from both microshoots and leaves of field-grown plants, as well as 1,8-cineole, demonstrated dose-dependent anti-proliferative and pro-apoptotic effects on CD4+ and CD8+ T cells. These findings highlight the potential of S. apiana microshoot cultures capable of producing EO with significant immunomodulatory activity.<\/jats:p>","DOI":"10.3390\/molecules30040815","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:08:51Z","timestamp":1739358531000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elicited Production of Essential Oil with Immunomodulatory Activity in Salvia apiana Microshoot Culture"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8929-2999","authenticated-orcid":false,"given":"Agata","family":"Krol","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5025-7101","authenticated-orcid":false,"given":"Adam","family":"Kokotkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1699-835X","authenticated-orcid":false,"given":"Bozena","family":"Zabiegala","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, Faculty of Chemistry, Gdansk University of Technology, 11\/12 Gabriela Narutowicza Street, 80-233 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0672-4136","authenticated-orcid":false,"given":"Klaudia","family":"Ciesielska-Figlon","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gdansk, M. Sk\u0142odowskiej-Curie 3a Street, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-4287","authenticated-orcid":false,"given":"Ewa","family":"Bryl","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gdansk, M. Sk\u0142odowskiej-Curie 3a Street, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-1109","authenticated-orcid":false,"given":"Jacek Maciej","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, Medical University of Gdansk, M. Sk\u0142odowskiej-Curie 3a Street, 80-211 Gdansk, Poland"},{"name":"Department of Embryology, Faculty of Medicine, Medical University of Gdansk, M. Sk\u0142odowskiej-Curie 3a Street, 80-211 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0558-9139","authenticated-orcid":false,"given":"Adam","family":"Bucinski","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Jagiellonska Street 15, 85-067 Bydgoszcz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5490-3588","authenticated-orcid":false,"given":"Maria","family":"Luczkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Gdansk, Gen. J. Hallera Street 107, 80-416 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vieira, S.F., Reis, R.L., Ferreira, H., and Neves, N.M. (2024). Plant-Derived Bioactive Compounds as Key Players in the Modulation of Immune-Related Conditions. Phytochem. Rev.","DOI":"10.1007\/s11101-024-09955-7"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1600\/036364415X689285","article-title":"Unravelling Species Relationships and Diversification within the Iconic California Floristic Province Sages (Salvia Subgenus Audibertia, Lamiaceae)","volume":"40","author":"Walker","year":"2015","journal-title":"Syst. Bot."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1055\/a-1453-0964","article-title":"White Sage (Salvia apiana)\u2014A Ritual and Medicinal Plant of the Chaparral: Plant Characteristics in Comparison with Other Salvia Species","volume":"88","author":"Krol","year":"2022","journal-title":"Planta Med."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Krol, A., Kokotkiewicz, A., Gorniak, M., Naczk, A.M., Zabiegala, B., Gebalski, J., Graczyk, F., Zaluski, D., Bucinski, A., and Luczkiewicz, M. (2023). Evaluation of the Yield, Chemical Composition and Biological Properties of Essential Oil from Bioreactor-Grown Cultures of Salvia apiana Microshoots. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-33950-1"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hu, J., Wang, F., Liang, F., Wu, Z., Jiang, R., Li, J., Chen, J., Qiu, S., Wang, J., and Zhang, Y. (2022). Identification of Abietane-Type Diterpenoids and Phenolic Acids Biosynthesis Genes in Salvia apiana Jepson Through Full-Length Transcriptomic and Metabolomic Profiling. Front. Plant Sci., 13.","DOI":"10.3389\/fpls.2022.919025"},{"key":"ref_6","unstructured":"Leopold, S. (2019). What Is Going on with White Sage?. J. Med. Plant Conserv., 3\u20135."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1007\/s00344-024-11294-y","article-title":"Elicitation: \u201cA Trump Card\u201d for Enhancing Secondary Metabolites in Plants","volume":"43","author":"Selwal","year":"2024","journal-title":"J. Plant Growth Regul."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1016\/j.indcrop.2018.07.013","article-title":"Elicitation Strategies for the Improvement of Essential Oil Content in Rhododendron tomentosum (Ledum palustre) Bioreactor-Grown Microshoots","volume":"123","author":"Jesionek","year":"2018","journal-title":"Ind. Crops Prod."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Calgaro, L.C., dos Santos Melisinas, V.A.P., Gon\u00e7alves, J.E., and Magalh\u00e3es, H.M. (2023). Biochemical Responses and Volatile Compounds in a Peppermint Chemotype Grown in a Controlled Environment. Res. Sq.","DOI":"10.21203\/rs.3.rs-2391173\/v1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1023\/A:1005396924568","article-title":"Improved Menthol Production from Chitosan-Elicited Suspension Culture of Mentha piperita","volume":"20","author":"Chang","year":"1998","journal-title":"Biotechnol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/ffj.3715","article-title":"Influence of Biotic and Abiotic Elicitors on Artemisinin, Quercetin, Caffeic Acid and Essential Oil Production in Artemisia dracunculus L","volume":"37","author":"Coskun","year":"2022","journal-title":"Flavour Fragr. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1007\/s11627-017-9868-8","article-title":"Volatile Essential Oil Chemical Composition of Basil (Ocimum basilicum L. \u2018Green\u2019) Cultivated in a Greenhouse and Micropropagated on a Culture Medium Containing Copper Sulfate","volume":"53","author":"Trettel","year":"2017","journal-title":"In Vitr. Cell. Dev. Biol.\u2014Plant"},{"key":"ref_13","first-page":"61","article-title":"Nitric Oxide Increased the Rosmarinic Acid and Essential Oil Production in In Vitro-Cultured Melissa officinalis","volume":"17","author":"Bahabadi","year":"2018","journal-title":"J. Med. Plants"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1007\/s12298-022-01215-2","article-title":"Plant Elicitation and TiO2 Nanoparticles Application as an Effective Strategy for Improving the Growth, Biochemical Properties, and Essential Oil of Peppermint","volume":"28","author":"Ganjeali","year":"2022","journal-title":"Physiol. Mol. Biol. Plants"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10529-013-1350-z","article-title":"Sage In Vitro Cultures: A Promising Tool for the Production of Bioactive Terpenes and Phenolic Substances","volume":"36","author":"Marchev","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00253-010-2797-7","article-title":"Tanshinone Biosynthesis in Salvia Miltiorrhiza and Production in Plant Tissue Cultures","volume":"88","author":"Wang","year":"2010","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.3390\/molecules17021698","article-title":"Ergosterol-Induced Sesquiterpenoid Synthesis in Tobacco Cells","volume":"17","author":"Tugizimana","year":"2012","journal-title":"Molecules"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/glycob\/cwp201","article-title":"Glycoconjugates as Elicitors or Suppressors of Plant Innate Immunity","volume":"20","author":"Silipo","year":"2009","journal-title":"Glycobiology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Riseh, R.S., Vazvani, M.G., and Kennedy, J.F. (2023). \u03b2\u2013Glucan-Induced Disease Resistance in Plants: A Review. Int. J. Biol. Macromol., 253.","DOI":"10.1016\/j.ijbiomac.2023.127043"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.1021\/np800573j","article-title":"Effects of Elicitors on Tropane Alkaloids and Gene Expression in Atropa baetica Transgenic Hairy Roots","volume":"71","author":"Barres","year":"2008","journal-title":"J. Nat. Prod."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11240-018-01553-8","article-title":"Elicitation of Isatis tinctoria L. Hairy Root Cultures by Salicylic Acid and Methyl Jasmonate for the Enhanced Production of Pharmacologically Active Alkaloids and Flavonoids","volume":"137","author":"Gai","year":"2019","journal-title":"Plant Cell Tissue Organ Cult. (PCTOC)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.biortech.2014.12.106","article-title":"Enhanced Camptothecin Production by Ethanol Addition in the Suspension Culture of the Endophyte, Fusarium solani","volume":"188","author":"Venugopalan","year":"2015","journal-title":"Bioresour. Technol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s11240-022-02252-1","article-title":"Enhancement of Phenolic Acids Accumulation in Salvia abrotanoides (Kar.) Sytsma Shoot Cultures Under Elicitation with Nitric Oxide","volume":"149","author":"Rostami","year":"2022","journal-title":"Plant Cell Tissue Organ Cult. (PCTOC)"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Contreras, A., Leroy, B., Mariage, P.A., and Wattiez, R. (2019). Proteomic Analysis Reveals Novel Insights into Tanshinones Biosynthesis in Salvia miltiorrhiza Hairy Roots. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-42164-3"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hubai, K., and Kov\u00e1ts, N. (2024). Interaction Between Heavy Metals Posed Chemical Stress and Essential Oil Production of Medicinal Plants. Plants, 13.","DOI":"10.3390\/plants13202938"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.indcrop.2018.03.021","article-title":"Essential Oil Composition and Total Phenolic, Flavonoid Contents, and Antioxidant Activity of Sage (Salvia officinalis L.) Extract Under Chitosan Application and Irrigation Frequencies","volume":"117","author":"Vosoughi","year":"2018","journal-title":"Ind. Crops Prod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1080\/10412905.2006.9699183","article-title":"Terpenoid Essential Oil Metabolism in Basil (Ocimum basilicum L.) Following Elicitation","volume":"18","author":"Deschamps","year":"2006","journal-title":"J. Essent. Oil Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115429","DOI":"10.1016\/j.indcrop.2022.115429","article-title":"Essential Oil Composition, Physiological and Morphological Variation in Salvia abrotanoides and S. yangii Under Drought Stress and Chitosan Treatments","volume":"187","author":"Khodadadi","year":"2022","journal-title":"Ind. Crops Prod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5967","DOI":"10.1021\/cr200058f","article-title":"Constituents from Salvia Species and Their Biological Activities","volume":"112","author":"Wu","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_30","first-page":"38","article-title":"Essential Oil Composition Variability in Sage (Salvia officinalis L.)","volume":"18","author":"Bernotiene","year":"2007","journal-title":"Chemija"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1021\/jf981170m","article-title":"Essential Oils from Dalmatian Sage (Salvia officinalis L.): Variations among Individuals, Plant Parts, Seasons, and Sites","volume":"47","author":"Perry","year":"1999","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104402","DOI":"10.1016\/j.fitote.2019.104402","article-title":"Chemical Variability of Rhododendron tomentosum (Ledum palustre) Essential Oils and Their Pro-Apoptotic Effect on Lymphocytes and Rheumatoid Arthritis Synoviocytes","volume":"139","author":"Jesionek","year":"2019","journal-title":"Fitoterapia"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ciesielska-Figlon, K., Daca, A., Kokotkiewicz, A., \u0141uczkiewicz, M., Zabiega\u0142a, B., Witkowski, J.M., and Lisowska, K.A. (2022). The Influence of Nigella Sativa Essential Oil on Proliferation, Activation, and Apoptosis of Human T Lymphocytes In Vitro. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113349"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1111\/cas.16086","article-title":"Antitumor Activity of \u03b1-Pinene in T-Cell Tumors","volume":"115","author":"Abe","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y.-P., Pan, F., Wang, Y.-D., Khan, A., Liu, Y.-P., Yang, M.-L., Cao, J.-X., Zhao, T.-R., and Cheng, G.-G. (2022). Anti-Leukemic Effect and Molecular Mechanism of 11-Methoxytabersonine from Melodinus Cochinchinensis via Network Pharmacology, ROS-Mediated Mitochondrial Dysfunction and PI3K\/Akt Signaling Pathway. Bioorg. Chem., 120.","DOI":"10.1016\/j.bioorg.2022.105607"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ciesielska-Figlon, K., Wojciechowicz, K., Daca, A., Kokotkiewicz, A., \u0141uczkiewicz, M., Witkowski, J.M., and Lisowska, K.A. (2023). The Impact of  Nigella sativa Essential Oil on T Cells in Women with Hashimoto\u2019s Thyroiditis. Antioxidants, 12.","DOI":"10.3390\/antiox12061246"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101391","DOI":"10.1016\/j.ctcp.2021.101391","article-title":"Essential Oil Therapy in Rheumatic Diseases: A Systematic Review: Essential Oils in Rheumatic Diseases","volume":"43","year":"2021","journal-title":"Complement. Ther. Clin. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Abd Rashed, A., Abd Rahman, A.Z., and Rathi, D.N.G. (2021). Essential Oils as a Potential Neuroprotective Remedy for Age-Related Neurodegenerative Diseases: A Review. Molecules, 26.","DOI":"10.3390\/molecules26041107"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Brown, S.K., Garver, W.S., and Orlando, R.A. (2017). 1,8-Cineole: An Underappreciated Anti-Inflammatory Therapeutic. J. Biomol. Res. Ther., 6.","DOI":"10.4172\/2167-7956.1000154"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1080\/10286020.2020.1839432","article-title":"1,8-Cineole: A Review of Source, Biological Activities, and Application","volume":"23","author":"Cai","year":"2021","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hoch, C.C., Petry, J., Griesbaum, L., Weiser, T., Werner, K., Ploch, M., Verschoor, A., Multhoff, G., Bashiri Dezfouli, A., and Wollenberg, B. (2023). 1,8-Cineole (Eucalyptol): A Versatile Phytochemical with Therapeutic Applications across Multiple Diseases. Biomed. Pharmacother., 167.","DOI":"10.1016\/j.biopha.2023.115467"},{"key":"ref_42","first-page":"508","article-title":"Inhibition of Cytokine Production and Arachidonic Acid Metabolism by Eucalyptol (1.8-Cineole) in Human Blood Monocytes In Vitro","volume":"3","author":"Juergens","year":"1998","journal-title":"Eur. J. Med. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.pupt.2004.06.002","article-title":"Inhibitory Activity of 1,8-Cineol (Eucalyptol) on Cytokine Production in Cultured Human Lymphocytes and Monocytes","volume":"17","author":"Juergens","year":"2004","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Abdalla, A.N., Shaheen, U., Abdallah, Q.M.A., Flamini, G., Bkhaitan, M.M., Abdelhady, M.I.S., Ascrizzi, R., and Bader, A. (2020). Proapoptotic Activity of Achillea membranacea Essential Oil and Its Major Constituent 1,8-Cineole Against A2780 Ovarian Cancer Cells. Molecules, 25.","DOI":"10.3390\/molecules25071582"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.3892\/or.2013.2763","article-title":"Antitumor Effect of 1, 8-Cineole against Colon Cancer","volume":"30","author":"Murata","year":"2013","journal-title":"Oncol. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1139\/b72-026","article-title":"Medium and Techniques for Induction and Growth of Monocotyledonous and Dicotyledonous Plant Cell Cultures","volume":"50","author":"Schenk","year":"1972","journal-title":"Can. J. Bot."},{"key":"ref_47","first-page":"9.25.1","article-title":"Advanced Application of CFSE for Cellular Tracking","volume":"44","author":"Witkowski","year":"2008","journal-title":"Curr. Protoc. Cytom."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/4\/815\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:30:25Z","timestamp":1760027425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/4\/815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,10]]},"references-count":47,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["molecules30040815"],"URL":"https:\/\/doi.org\/10.3390\/molecules30040815","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2025,2,10]]}}}