{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:04:44Z","timestamp":1785416684271,"version":"3.56.0"},"reference-count":34,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T00:00:00Z","timestamp":1783814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031311","name":"Wroclaw University of Economics and Business","doi-asserted-by":"crossref","award":["Otwarta Nauka"],"award-info":[{"award-number":["Otwarta Nauka"]}],"id":[{"id":"10.13039\/100031311","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Otwarta Nauka"],"award-info":[{"award-number":["Otwarta Nauka"]}],"id":[{"id":"https:\/\/ror.org\/013sm1c65","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sideritis species (Lamiaceae), the aromatic mountain teas of the Mediterranean and Balkans, accumulate a phytochemically rich array of bioactive compounds\u2014phenylethanoid glycosides (notably verbascoside), flavonoid aglycones and glycosides, phenolic acids, and terpenoids\u2014whose pharmacological relevance is increasingly defined at the molecular level. This review synthesizes current evidence on the molecular mechanisms through which these constituents act in human health and disease, integrating in vitro, in vivo, in silico, and clinical data. Anti-inflammatory activity is attributed to modulation of the NF-\u03baB and NLRP3 inflammasome pathways; direct verbascoside binding to both targets has been demonstrated in vitro by microscale thermophoresis (nanomolar-to-micromolar Kd), with suppression of TNF-\u03b1 and IL-1\u03b2 observed in cell-based and animal models. Neuroprotective effects are proposed to operate through amyloid-\u03b2 clearance via ADAM10 upregulation and enhanced microglial phagocytosis in transgenic mouse models, together with in vitro triple monoamine (serotonin, noradrenaline, dopamine) reuptake inhibition, and are supported at the functional level by small randomized clinical trials reporting cognitive and anxiolytic benefits. Antioxidant and cytoprotective actions reflect radical scavenging, metal chelation, and restoration of SOD\/CAT\/GSH with attenuation of lipid peroxidation, underpinning documented hepatoprotective and gastroprotective outcomes. Preliminary cardiometabolic findings from small clinical trials include cholesterol modulation and sex-dependent effects on insulin sensitivity that remain to be confirmed in larger, adequately powered cohorts. We further evaluate structure\u2013activity relationships, species- and tissue-level chemical variability, and green extraction strategies relevant to standardized bioactivity-preserving preparations. Critical gaps\u2014in vivo validation of antiproliferative effects documented only in cell-based and in silico studies so far, systematic toxicological assessment, and bioavailability characterization\u2014are identified to guide translation. Collectively, Sideritis-derived phytochemicals, exemplified by S. scardica, represent a mechanistically coherent group of plant bioactives with defined molecular targets in inflammatory, neurodegenerative, and metabolic disorders.<\/jats:p>","DOI":"10.3390\/ijms27146217","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:53:58Z","timestamp":1783932838000},"page":"6217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioactive Compounds of Sideritis Species in Inflammation, Neuroprotection and Cardiometabolic Health: A Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Gonxhe Kajtazi","family":"\u00c7itaku","sequence":"first","affiliation":[{"name":"Department of Food Technology, Faculty of Food Technology, University \u2018\u2019Isa Boletini\u2019 Str. Ukshin Kovacica, 40000 Mitrovica, Kosovo"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-7106","authenticated-orcid":false,"given":"Joanna","family":"Harasym","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Analysis, Wroclaw University of Economics and Business, Komandorska 118\/120, 53-345 Wroclaw, Poland"},{"name":"Adaptive Food Systems Accelerator-Science Centre, Wroclaw University of Economics and Business, 53-345 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"\u017by\u017celewicz, D., Kulbat-Warycha, K., Oracz, J., and \u017by\u017celewicz, K. (2020). Polyphenols and Other Bioactive Compounds of Sideritis Plants and Their Potential Biological Activity. 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