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To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a selected group of monoterpenes especially abundant in mint species was screened by measuring bacterial lipopolysacharide (LPS)-induced nitric oxide (NO) production in murine macrophages. Nine compounds significantly decreased LPS-induced NO production by more than 30%. IC<jats:sub>50<\/jats:sub> values were calculated showing that the order of potency is: (S)-(+)-carvone\u2009&gt;\u2009(R)-(\u2212)-carvone\u2009&gt;\u2009(+)-dihydrocarveol\u2009&gt;\u2009(S)-8-hydroxycarvotanacetone\u2009&gt;\u2009(R)-8-hydroxycarvotanacetone\u2009&gt;\u2009(+)-dihydrocarvone\u2009&gt;\u2009(\u2212)-carveol\u2009&gt;\u2009(\u2212)-dihydrocarveol\u2009&gt;\u2009(S)-(-)-pulegone. Considering the carbon numbering relative to the common precursor, limonene, the presence of an oxygenated group at C6 conjugated to a double bond at C1 and an isopropenyl group and S configuration at C4 are the major chemical features relevant for activity and potency. The most potent compound, (S)-(+)-carvone, significantly decreased the expression of NOS2 and IL-1\u03b2 in macrophages and in a cell model of osteoarthritis using primary human chondrocytes. (S)-(+)-carvone may be efficient in halting inflammation-related diseases, like osteoarthritis.<\/jats:p>","DOI":"10.1038\/s41598-020-64032-1","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T10:03:17Z","timestamp":1588154597000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Standardised comparison of limonene-derived monoterpenes identifies structural determinants of anti-inflammatory activity"],"prefix":"10.1038","volume":"10","author":[{"given":"C\u00e1tia","family":"Sousa","sequence":"first","affiliation":[]},{"given":"Alcino Jorge","family":"Leit\u00e3o","sequence":"additional","affiliation":[]},{"given":"Bruno Miguel","family":"Neves","sequence":"additional","affiliation":[]},{"given":"Fernando","family":"Judas","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Cavaleiro","sequence":"additional","affiliation":[]},{"given":"Alexandrina Ferreira","family":"Mendes","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,4,29]]},"reference":[{"key":"64032_CR1","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1096\/fj.201601326R","volume":"31","author":"M Antonelli","year":"2017","unstructured":"Antonelli, M. & Kushner, I. 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