{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T17:16:06Z","timestamp":1783185366043,"version":"3.54.6"},"reference-count":65,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lodz, Poland","award":["503\/3-022-01\/503-31-001"],"award-info":[{"award-number":["503\/3-022-01\/503-31-001"]}]},{"name":"Medical University of Lodz, Poland","award":["503\/3-015-02\/503-31-001"],"award-info":[{"award-number":["503\/3-015-02\/503-31-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(6S,9R)-vomifoliol (VO) is a natural norisoprenoid of the megastigmane type derived from Gaultheria procumbens, an aromatic, evergreen shrub whose leaves, fruits, and aerial parts are used in traditional phytotherapy to treat oxidative stress and inflammation-related disorders. The plant is known as a rich source of essential oil and polyphenols. However, the levels of other constituents of G. procumbens, including VO, have yet to be explored. There is also a knowledge gap in the pharmacological potential of VO in the context of inflammation. Therefore, the present study aimed to investigate the accumulation of VO in leaves, stems, and fruits of G. procumbens and to determine its antioxidant and anti-inflammatory effects in non-cellular in vitro and cell-based models of human immune cells ex vivo. The GC-FID-MS (gas chromatography coupled with flame ionisation detector and mass spectrometer) analysis revealed the leaves as the richest source of VO (0.36 mg\/g dw of the plant material) compared to other G. procumbens organs. In non-cellular activity tests, VO showed comparable to positive control anti-inflammatory activity against lipoxygenase, with significantly weaker impact on hyaluronidase and cyclooxygenase-2, and no effect on cyclooxygenase-1 isozyme. VO at 5\u201375 \u03bcM revealed a significant and dose-dependent ability to reduce the reactive oxygen species (ROS) level, downregulate the release of pro-inflammatory cytokines [tumour necrosis factor-\u03b1 (TNF-\u03b1), interleukin-8 (IL-8), IL-6, and IL-1\u03b2] and tissue-remodelling enzymes (elastase-2, metalloproteinase-9), and up-regulate the secretion of anti-inflammatory cytokine IL-10 in bacterial lipopolysaccharide (LPS)- and N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP)-stimulated human neutrophils and peripheral blood mononuclear cells (PBMCs) ex vivo. Furthermore, a significant reduction in IL-6, lipoxygenase (LOX), nuclear factor \u03ba-light-chain-enhancer of activated B cells 1 (NF-\u03baB1), and NF-\u03baB2 gene expression in LPS-stimulated peripheral blood lymphocytes was demonstrated by real-time PCR. The cellular safety of VO at 5\u201375 \u03bcM was confirmed by flow cytometry, with the viability of neutrophils and PBMCs after incubation with VO at 93.8\u201398.4%. The results encourage further studies of VO as a promising non-cytotoxic natural anti-inflammatory agent and support the use of leaves of G. procumbens in the adjuvant treatment of oxidative stress and inflammation-related diseases of affluence.<\/jats:p>","DOI":"10.3390\/ijms26041571","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T05:10:22Z","timestamp":1739423422000},"page":"1571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Anti-Inflammatory and Antioxidant Effects of (6S,9R)-Vomifoliol from Gaultheria procumbens L.: In Vitro and Ex Vivo Study in Human Immune Cell Models"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-2339","authenticated-orcid":false,"given":"Piotr","family":"Michel","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2134-2654","authenticated-orcid":false,"given":"Anna","family":"Wajs-Bonikowska","sequence":"additional","affiliation":[{"name":"Institute of Natural Products and Cosmetics, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2\/22, 90-537 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2437-3242","authenticated-orcid":false,"given":"Anna","family":"Magiera","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1732-0233","authenticated-orcid":false,"given":"Agnieszka","family":"Wosiak","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5257-2914","authenticated-orcid":false,"given":"Ewa","family":"Balcerczak","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8159-0174","authenticated-orcid":false,"given":"Monika Ewa","family":"Czerwi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland"},{"name":"Centre for Preclinical Research, Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8468-1365","authenticated-orcid":false,"given":"Monika Anna","family":"Olszewska","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Medical University of Lodz, Muszy\u0144skiego 1, 90-151 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.phytol.2024.01.008","article-title":"Comprehensive review on megastigmane glycosides: Sources, bioactivities, and 13C NMR spectroscopic data","volume":"60","author":"Samra","year":"2024","journal-title":"Phytochem. 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