{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T15:57:19Z","timestamp":1770911839990,"version":"3.50.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":105,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"SATREPS Project","award":["JPMJSA1506"],"award-info":[{"award-number":["JPMJSA1506"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>Squalene (SQ), a natural precursor of many steroids, can inhibit tumor progression and decrease serum cholesterol levels. However, it is difficult to discern the effect of highly active molecules in the treatment of diseases because not enough active compounds reach the site of pathology in crowded biosystems. Therefore, it is necessary to design artificial probes that work effectively within crowded systems. In this study, to facilitate cell penetration, the ethylene glycol moiety (used as a probe) was chemically added to SQ to form 2\u2010(2\u2010hydroxyethoxy)\u20103\u2010hydroxysqualene (HEHSQ). HEHSQ was prepared from 2,3\u2010epoxysqualene and characterized by R<jats:sub>f<\/jats:sub>, FT\u2010IR, <jats:sup>1<\/jats:sup>H NMR, <jats:sup>13<\/jats:sup>C NMR, and high\u2010resolution mass spectrometry. We then evaluated the anti\u2010inflammatory effects of SQ and HEHSQ on lipopolysaccharide\u2010 (LPS\u2010) stimulated RAW264.7 murine macrophages. To determine the effect of SQ and HEHSQ on the viability of RAW264.7 cells, an MTT assay was performed. To quantify the anti\u2010inflammatory effect of SQ and HEHSQ, we measured nitric oxide (NO) production, gene expression, and secretion of the proinflammatory cytokine tumor necrosis factor <jats:italic>\u03b1<\/jats:italic> (TNF\u2010<jats:italic>\u03b1<\/jats:italic>) and chemokine C\u2010C motif chemokine 2 (CCL2) in LPS\u2010stimulated RAW264.7 cells using an <jats:italic>in vitro<\/jats:italic> inflammatory model. 2,3\u2010Epoxysqualene was prepared according to a reported methodology. The reaction of 2,3\u2010epoxysqualene and ethylene glycol in 2\u2010propanol produced 49% HEHSQ. MTT results showed that 10 and 100\u2009<jats:italic>\u00b5<\/jats:italic>g\/mL HEHSQ treatment decreased cell viability, whereas SQ treatment (1\u2013100\u2009<jats:italic>\u00b5<\/jats:italic>g\/mL) did not have any effect on viability. SQ (100\u2009<jats:italic>\u00b5<\/jats:italic>g\/mL) and HEHSQ (1\u2009<jats:italic>\u00b5<\/jats:italic>g\/mL) treatment significantly reduced the production of LPS\u2010stimulated NO and decreased the expression and secretion of proinflammatory TNF\u2010<jats:italic>\u03b1<\/jats:italic> and CCL2. Therefore, our results suggested that the anti\u2010inflammatory effects of HEHSQ are 100 times higher than that of unmodified SQ. To the best of our knowledge, this study has demonstrated for the first time that HEHSQ can be potentially used as a safe alternative treatment to anti\u2010inflammatory drugs.<\/jats:p>","DOI":"10.1155\/2020\/9584567","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T23:37:51Z","timestamp":1586993871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Synthesis of 2\u2010(2\u2010Hydroxyethoxy)\u20103\u2010hydroxysqualene and Characterization of Its Anti\u2010Inflammatory Effects"],"prefix":"10.1155","volume":"2020","author":[{"given":"Kazunori","family":"Sasaki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Inami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideo","family":"Kigoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0790-4048","authenticated-orcid":false,"given":"Takashi","family":"Arimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-9541","authenticated-orcid":false,"given":"Hiroko","family":"Isoda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.5053\/ejobios.2009.3.0.17"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2016.02.025"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3073"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.35.040195.003255"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/s30800276"},{"key":"e_1_2_11_6_2","first-page":"32","article-title":"The role of chronic inflammation in cardiovascular disease and its regulation by nutrients","volume":"9","author":"Osiecki H.","year":"2004","journal-title":"Alternative Medicine Review"},{"key":"e_1_2_11_7_2","first-page":"826","article-title":"Overproduction of nitric oxide in pathophysiology of blood vessels","volume":"63","author":"Stoclet J. 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