{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:22:11Z","timestamp":1790709731019,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T00:00:00Z","timestamp":1643673600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002531","name":"Kyungpook National University","doi-asserted-by":"publisher","award":["University Development Project Research Fund, 2019"],"award-info":[{"award-number":["University Development Project Research Fund, 2019"]}],"id":[{"id":"10.13039\/501100002531","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Classically activated M1 macrophages reprogram their metabolism towards enhanced glycolysis to obtain energy and produce pro-inflammatory cytokines after activation by mammalian target of rapamycin complex 1 (mTORC1) and hypoxia-inducible factor (HIF)-1\u03b1. Thus, a strategy that constrains M1 polarization of macrophages via downregulation of glycolysis is essential for treating chronic inflammatory diseases. Cassiae semen has pharmacological activity against various inflammatory diseases. However, it is unclear whether specific compounds within Cassia seeds affect M1 polarization of macrophages. Here, we investigated whether Cassiaside C napthopyrone from Cassiae semen inhibits M1 polarization by downregulating glycolysis. We found that Cassiaside C reduced expression of inducible nitric oxide synthase and cyclooxygenase-2 and the phosphorylation of nuclear factor kappa B, all of which are upregulated in lipopolysaccharide (LPS)\/interferon (IFN)-\u03b3-treated Raw264.7 cells and peritoneal macrophages. Moreover, Cassiaside C-treated macrophages showed marked suppression of LPS\/IFN-\u03b3-induced HIF-1\u03b1, pyruvate dehydrogenase kinase 1, and lactate dehydrogenase A expression, along with downregulation of the phosphoinositide 3-kinases (PI3K)\/AKT\/mTORC1 signaling pathway. Consequently, Cassiaside C attenuated enhanced glycolysis and lactate production, but rescued diminished oxidative phosphorylation, in M1 polarized macrophages. Thus, Cassiaside C dampens M1 polarization of macrophages by downregulating glycolysis, which could be exploited as a therapeutic strategy for chronic inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms23031696","type":"journal-article","created":{"date-parts":[[2022,2,1]],"date-time":"2022-02-01T09:59:21Z","timestamp":1643709561000},"page":"1696","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cassiaside C Inhibits M1 Polarization of Macrophages by Downregulating Glycolysis"],"prefix":"10.3390","volume":"23","author":[{"given":"Ye Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea"},{"name":"Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoo","family":"Lee","sequence":"additional","affiliation":[{"name":"New Drug Development Center, Daegu Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonghwa","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyein","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Kyung","family":"Choi","sequence":"additional","affiliation":[{"name":"Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41566, Korea"},{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu 41404, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8403-1298","authenticated-orcid":false,"given":"Keun-Gyu","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu 41944, Korea"},{"name":"Research Institute of Aging and Metabolism, Kyungpook National University, Daegu 41566, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Cantley","year":"2009","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2007.10.002","article-title":"The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation","volume":"7","author":"DeBerardinis","year":"2008","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Park, H.Y., Kim, M.J., Lee, S., Jin, J., Lee, S., Kim, J.G., Choi, Y.K., and Park, K.G. 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