{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:14:09Z","timestamp":1790957649997,"version":"4.1.0"},"reference-count":126,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc\u2013curcumin Zn (II)\u2013curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc\u2013curcumin Zn (II)\u2013curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62\/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62\/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives\/analogs via regulation of Nrf2 regulation.<\/jats:p>","DOI":"10.3390\/molecules27010167","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T02:31:27Z","timestamp":1640745087000},"page":"167","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":153,"title":["Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects"],"prefix":"10.3390","volume":"27","author":[{"given":"Seyed Hossein","family":"Shahcheraghi","sequence":"first","affiliation":[{"name":"Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd 8916978477, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fateme","family":"Salemi","sequence":"additional","affiliation":[{"name":"School of Medicine, Islamic Azad University of Medical Sciences, Yazd 19395\/1495, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloufar","family":"Peirovi","sequence":"additional","affiliation":[{"name":"School of Medicine, Tehran University of Medical Sciences, Tehran 1417614411, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamshid","family":"Ayatollahi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Research Center, Shahid Sadoughi Hospital, Shahid Sadoughi University of Medical Sciences, Yazd 8916978477, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8329-9180","authenticated-orcid":false,"given":"Waqas","family":"Alam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haroon","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4530-8706","authenticated-orcid":false,"given":"Luciano","family":"Saso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cVittorio Erspamer\u201d, Sapienza University, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.phymed.2010.11.007","article-title":"Modulation of pentylenetetrazole-induced kindling and oxidative stress by curcumin in mice","volume":"18","author":"Agarwal","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"106131","DOI":"10.1016\/j.intimp.2019.106131","article-title":"Dimethyl fumarate and curcumin attenuate hepatic ischemia\/reperfusion injury via Nrf2\/HO-1 activation and anti-inflammatory properties","volume":"80","author":"Ibrahim","year":"2020","journal-title":"Int. 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