Editing GSK-3 (section)

===Curcumin===
Curcumin, which Is a constituent of [[turmeric]] spice, has flavoring and coloring properties.<ref>{{cite journal | vauthors = Maheshwari RK, Singh AK, Gaddipati J, Srimal RC | title = Multiple biological activities of curcumin: a short review | journal = Life Sciences | volume = 78 | issue = 18 | pages = 2081–2087 | date = March 2006 | pmid = 16413584 | doi = 10.1016/j.lfs.2005.12.007 }}</ref> It has two symmetrical forms: enol (the most abundant forms) and ketone.<ref>{{cite journal | vauthors = Balasubramanian K | title = Molecular orbital basis for yellow curry spice curcumin's prevention of Alzheimer's disease | journal = Journal of Agricultural and Food Chemistry | volume = 54 | issue = 10 | pages = 3512–3520 | date = May 2006 | pmid = 19127718 | doi = 10.1021/jf0603533 | bibcode = 2006JAFC...54.3512B }}</ref><ref>{{cite journal | vauthors = Payton F, Sandusky P, Alworth WL | title = NMR study of the solution structure of curcumin | journal = Journal of Natural Products | volume = 70 | issue = 2 | pages = 143–146 | date = February 2007 | pmid = 17315954 | doi = 10.1021/np060263s | bibcode = 2007JNAtP..70..143P }}</ref>

Curcumin has wide pharmacological activities: anti-inflammatory,<ref>{{cite journal | vauthors = Kohli K, Ali J, Ansari MJ, Raheman Z |doi=10.4103/0253-7613.16209 |title=Curcumin: A natural antiinflammatory agent |journal=Indian Journal of Pharmacology |volume=37 |issue=3 |pages=141 |year=2005 |url=http://www.bioline.org.br/pdf?ph05037 |doi-access=free |hdl=1807/8668 |hdl-access=free }}</ref> anti-microbial,<ref>{{cite journal | vauthors = Negi PS, Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK | title = Antibacterial activity of turmeric oil: a byproduct from curcumin manufacture | journal = Journal of Agricultural and Food Chemistry | volume = 47 | issue = 10 | pages = 4297–4300 | date = October 1999 | pmid = 10552805 | doi = 10.1021/jf990308d | bibcode = 1999JAFC...47.4297N }}</ref> hypoglycemic, anti-oxidant, and wound healing effects.<ref>{{cite journal | vauthors = Sidhu GS, Singh AK, Thaloor D, Banaudha KK, Patnaik GK, Srimal RC, Maheshwari RK | title = Enhancement of wound healing by curcumin in animals | journal = Wound Repair and Regeneration | volume = 6 | issue = 2 | pages = 167–177 | year = 1998 | pmid = 9776860 | doi = 10.1046/j.1524-475X.1998.60211.x | s2cid = 21440334 }}</ref> In animal models with Alzheimer disease, it has anti-destructive effect of beta amyloid in the brain,<ref>{{cite journal | vauthors = Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM | display-authors = 6 | title = Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo | journal = The Journal of Biological Chemistry | volume = 280 | issue = 7 | pages = 5892–5901 | date = February 2005 | pmid = 15590663 | doi = 10.1074/jbc.M404751200 | doi-access = free }}</ref> and recently it shows anti-malarial activity.<ref>{{cite journal | vauthors = Mishra S, Karmodiya K, Surolia N, Surolia A | title = Synthesis and exploration of novel curcumin analogues as anti-malarial agents | journal = Bioorganic & Medicinal Chemistry | volume = 16 | issue = 6 | pages = 2894–2902 | date = March 2008 | pmid = 18194869 | doi = 10.1016/j.bmc.2007.12.054 }}</ref>

Curcumin also has chemo preventative and anti-cancer effects,{{cn|date=September 2024}} and it has been shown to attenuate oxidative stress and renal dysfunction in diabetic animals with chronic use.<ref>{{cite journal | vauthors = Sharma S, Kulkarni SK, Chopra K | title = Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats | journal = Clinical and Experimental Pharmacology & Physiology | volume = 33 | issue = 10 | pages = 940–945 | date = October 2006 | pmid = 17002671 | doi = 10.1111/j.1440-1681.2006.04468.x | s2cid = 25193929 }}</ref>

Curcumin's mechanism of action is anti-inflammatory; it inhibits the nuclear transcriptional activator kappa B ([[NF-κB|NF-KB]]) that is activated whenever there is inflammatory response.{{citation needed|date=February 2019}}

[[NF-kB]] has two regulatory factors, IkB and GSK-3,<ref>{{cite journal | vauthors = Demarchi F, Bertoli C, Sandy P, Schneider C | title = Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability | journal = The Journal of Biological Chemistry | volume = 278 | issue = 41 | pages = 39583–39590 | date = October 2003 | pmid = 12871932 | doi = 10.1074/jbc.M305676200 | doi-access = free }}</ref> which suggests curcumin directly binds and inhibits GSK-3B. An in vitro study confirmed GSK-3B inhibition by simulating molecular docking using a silico docking technique.<ref name="Bustanji_2009">{{cite journal | vauthors = Bustanji Y, Taha MO, Almasri IM, Al-Ghussein MA, Mohammad MK, Alkhatib HS | title = Inhibition of glycogen synthase kinase by curcumin: Investigation by simulated molecular docking and subsequent in vitro/in vivo evaluation | journal = Journal of Enzyme Inhibition and Medicinal Chemistry | volume = 24 | issue = 3 | pages = 771–778 | date = June 2009 | pmid = 18720192 | doi = 10.1080/14756360802364377 | s2cid = 23137441 }}</ref> The concentration at which 50% of GK-3B would be inhibited by curcumin is 66.3 nM.<ref name="Bustanji_2009" />

Among its two forms, experimental and theoretical studies show that the enol form is the favored form due to its intra-molecular hydrogen bonding, and an NMR experiment show that enol form exist in a variety of solvents.{{citation needed|date=February 2019}}