View source for Crocin

{{Short description|Carotenoid chemical compound}}
{{About|a naturally occurring compound|the Indian brand of painkiller of the same name|paracetamol}}
{{Chembox
| ImageFile = crocin.png
| ImageSize = 250px
| IUPACName = Bis[β-<small>D</small>-glucopyranosyl-(1→6)-β-<small>D</small>-glucopyranosyl] 8,8′-diapocarotene-8,8′-dioate
| SystematicName = Bis[(2''S'',3''R'',4''S'',5''S'',6''R'')-3,4,5-trihydroxy-6-({[(2''R'',3''R'',4''S'',5''S'',6''R'')-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl] (2''E'',4''E'',6''E'',8''E'',10''E'',12''E'',14''E'')-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate
| OtherNames =
|Section1={{Chembox Identifiers
| CASNo = 42553-65-1
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 877GWI46C2
| PubChem = 5281233
| ChemSpiderID = 4444645
| ChEBI = 79068
| SMILES = O=C(O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)CO[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)\C(=C\C=C\C(=C\C=C\C=C(\C=C\C=C(\C(=O)O[C@@H]4O[C@H](CO[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)[C@@H](O)[C@H](O)[C@H]4O)C)C)C)C
| InChI = 1/C44H64O24/c1-19(11-7-13-21(3)39(59)67-43-37(57)33(53)29(49)25(65-43)17-61-41-35(55)31(51)27(47)23(15-45)63-41)9-5-6-10-20(2)12-8-14-22(4)40(60)68-44-38(58)34(54)30(50)26(66-44)18-62-42-36(56)32(52)28(48)24(16-46)64-42/h5-14,23-38,41-58H,15-18H2,1-4H3/b6-5+,11-7+,12-8+,19-9+,20-10+,21-13+,22-14+/t23-,24-,25-,26-,27-,28-,29-,30-,31+,32+,33+,34+,35-,36-,37-,38-,41-,42-,43+,44+/m1/s1
| InChIKey = SEBIKDIMAPSUBY-RTJKDTQDBE
| StdInChI = 1S/C44H64O24/c1-19(11-7-13-21(3)39(59)67-43-37(57)33(53)29(49)25(65-43)17-61-41-35(55)31(51)27(47)23(15-45)63-41)9-5-6-10-20(2)12-8-14-22(4)40(60)68-44-38(58)34(54)30(50)26(66-44)18-62-42-36(56)32(52)28(48)24(16-46)64-42/h5-14,23-38,41-58H,15-18H2,1-4H3/b6-5+,11-7+,12-8+,19-9+,20-10+,21-13+,22-14+/t23-,24-,25-,26-,27-,28-,29-,30-,31+,32+,33+,34+,35-,36-,37-,38-,41-,42-,43+,44+/m1/s1
| StdInChIKey = SEBIKDIMAPSUBY-RTJKDTQDSA-N
}}
|Section2={{Chembox Properties
| C=44 | H=64 | O=24
| Appearance =
| Density =
| MeltingPt =
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|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
}}
}}
'''Crocin''' is a [[carotenoid]] chemical compound that is found in the flowers of [[crocus]] and [[gardenia]].<ref>{{cite web |url=http://sun.ars-grin.gov:8080/npgspub/xsql/duke/chemdisp.xsql?chemical=CROCIN |title=Chemical Information |publisher=sun.ars-grin.gov |access-date=2008-03-02 |archive-url=https://web.archive.org/web/20041108234208/http://sun.ars-grin.gov:8080/npgspub/xsql/duke/chemdisp.xsql?chemical=CROCIN |archive-date=2004-11-08 |url-status=dead }}</ref> Its oxygen content also chemically makes it a [[xanthene]]. Crocin is the chemical primarily responsible for the color of [[saffron]].
Chemically, crocin is the [[ester|diester]] formed from the [[disaccharide]] [[gentiobiose]] and the [[dicarboxylic acid]] [[crocetin]]. When isolated as a pure chemical compound, it has a deep red color and forms crystals with a melting point of 186&nbsp;°C. When dissolved in water, it forms an orange solution.
The term ''crocins'' may also refer to members of a series of related [[hydrophile|hydrophilic]] carotenoids that are either [[glycosyl|monoglycosyl]] or diglycosyl [[polyene]] esters of crocetin.<ref name="Abdullaev_2002">{{cite journal | vauthors = Abdullaev FI | title = Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.) | journal = Experimental Biology and Medicine | volume = 227 | issue = 1 | pages = 20–25 | date = January 2002 | pmid = 11788779 | doi = 10.1177/153537020222700104 | s2cid = 40798771 }}</ref> The crocin underlying saffron's aroma is α-crocin (a carotenoid pigment that may compose more than 10% of dry saffron's mass): trans-[[crocetin]] di-(β-D-[[gentiobiose|gentiobiosyl]]) [[ester]]; it bears the [[IUPAC nomenclature|systematic (IUPAC) name]] 8,8-diapo-8,8-carotenoic acid.<ref name="Abdullaev_2002" />{{rp|20}}
The major active component of saffron is the yellow pigment crocin 2 (three other derivatives with different glycosylations are known) containing a gentiobiose (disaccharide) group at each end of the molecule. The five major biologically active components of saffron, namely the four crocins and crocetin, can be measured with HPLC-UV.<ref name=Li999>{{cite journal | vauthors = Li N, Lin G, Kwan YW, Min ZD | title = Simultaneous quantification of five major biologically active ingredients of saffron by high-performance liquid chromatography | journal = Journal of Chromatography A | volume = 849 | issue = 2 | pages = 349–355 | date = July 1999 | pmid = 10457433 | doi = 10.1016/S0021-9673(99)00600-7 }}</ref>
== Research ==
=== Absorption ===
Crocin ingested orally is hydrolised to crocetin in the gut which is absorbed across the intestinal barrier, and that crocetin can permeate the [[blood–brain barrier]].<ref>{{cite book |title=Chapter 1 - Biochemistry and metabolism |vauthors=Popović-Djordjević JB, Stanković JS, Mihailović V, Akram M |date=2021-01-01 |journal=Saffron |publisher=Academic Press |isbn=978-0-12-821219-6 |veditors=Galanakis CM |pages=1–40 |language=en |chapter=Chapter 1 - Biochemistry and metabolism∗ |doi=10.1016/b978-0-12-821219-6.00001-4 |access-date=2022-08-20 |chapter-url=https://www.sciencedirect.com/science/article/pii/B9780128212196000014 |s2cid=228897923}}</ref><ref>{{cite journal | vauthors = Lautenschläger M, Sendker J, Hüwel S, Galla HJ, Brandt S, Düfer M, Riehemann K, Hensel A | display-authors = 6 | title = Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier | journal = Phytomedicine | volume = 22 | issue = 1 | pages = 36–44 | date = January 2015 | pmid = 25636868 | doi = 10.1016/j.phymed.2014.10.009 }}</ref>
=== Antioxidant ===
Crocin has been shown to be an [[antioxidant]],<ref name="aggregation-Papandreou">{{cite journal | vauthors = Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, Lamari FN | title = Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents | journal = Journal of Agricultural and Food Chemistry | volume = 54 | issue = 23 | pages = 8762–8768 | date = November 2006 | pmid = 17090119 | doi = 10.1021/jf061932a }}</ref><ref name="Crocin-DFT">{{cite journal |author1=Akhtari K |author2=Hassanzadeh K |author3=Fakhraei B |author4=Fakhraei N |author5=Hassanzadeh H |author6=Zarei S A |title= A density functional theory study of the reactivity descriptors and antioxidant behavior of Crocin |journal=Computational and Theoretical Chemistry |year=2013 |pages=123–129 |volume=1013 |doi=10.1016/j.comptc.2013.03.015}}</ref> and neural protective agent.<ref name="carotenoids-Ochiai">{{cite journal | vauthors = Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, Shoyama Y, Toda A, Eyanagi R, Soeda S | display-authors = 6 | title = Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1770 | issue = 4 | pages = 578–584 | date = April 2007 | pmid = 17215084 | doi = 10.1016/j.bbagen.2006.11.012 | name-list-style = vanc }}</ref><ref name="oxidativestress-Zheng">{{cite journal | vauthors = Zheng YQ, Liu JX, Wang JN, Xu L | title = Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia | journal = Brain Research | volume = 1138 | pages = 86–94 | date = March 2007 | pmid = 17274961 | doi = 10.1016/j.brainres.2006.12.064 | s2cid = 25495517 }}</ref> Crocin can reduce oxidative stress and ROS ([[Reactive oxygen species|Reactive Oxygen Species]]) through enhancement of gene expression of Nrf2, HO-1, and anti-oxidant enzymes, such as CAT, GSH, and SOD.<ref>{{Cite journal | vauthors = Khoshandam A, Razavi BM, Hosseinzadeh H |date= July 2022 |title=Interaction of saffron and its constituents with Nrf2 signaling pathway: A review |journal=Iranian Journal of Basic Medical Sciences |volume=25 |issue=7 |pages=789–798 |doi=10.22038/ijbms.2022.61986.13719 |pmid= 36033950 |pmc= 9392575 |issn=2008-3866}}</ref><ref name="Abdullaev_2002" /><ref name="Crocin-DFT" />
=== Neuroprotective ===
Crocin and its derivative crocetin may counteract oxidative stress, mitochondrial dysfunction and neuroinflammation, which are closely linked to initiation and progression of major brain pathologies such as [[Alzheimer's disease|Alzheimer's]] and [[Parkinson's disease]].<ref>{{cite journal | vauthors = Scuto M, Modafferi S, Rampulla F, Zimbone V, Tomasello M, Spano' S, Ontario ML, Palmeri A, Trovato Salinaro A, Siracusa R, Di Paola R, Cuzzocrea S, Calabrese EJ, Wenzel U, Calabrese V | display-authors = 6 | title = Redox modulation of stress resilience by Crocus sativus L. for potential neuroprotective and anti-neuroinflammatory applications in brain disorders: From molecular basis to therapy | journal = Mechanisms of Ageing and Development | volume = 205 | pages = 111686 | date = July 2022 | pmid = 35609733 | doi = 10.1016/j.mad.2022.111686 | s2cid = 248950035 }}</ref>
In an animal model of malathion-induced Parkinson's disease, crocin reduced the neurotoxic effect of malathion by its anti-apoptotic activity and  it regulated the expression of proteins involved in Parkinson's disease pathogenesis.<ref>{{cite journal | vauthors = Mohammadzadeh L, Ghasemzadeh Rahbardar M, Razavi BM, Hosseinzadeh H | title = Crocin Protects Malathion-Induced Striatal Biochemical Deficits by Inhibiting Apoptosis and Increasing α-Synuclein in Rats' Striatum | journal = Journal of Molecular Neuroscience | volume = 72 | issue = 5 | pages = 983–993 | date = May 2022 | pmid = 35274200 | doi = 10.1007/s12031-022-01990-3 | s2cid = 247383603 }}</ref>
Crocins can suppress the active forms of GSK3β and ERK1/2 kinases,  significantly reducing  tau phosphorylation, thus suppressing key molecular pathways of Alzheimer's disease pathogenesis.<ref>{{cite journal | vauthors = Chalatsa I, Arvanitis DA, Koulakiotis NS, Giagini A, Skaltsounis AL, Papadopoulou-Daifoti Z, Tsarbopoulos A, Sanoudou D | display-authors = 6 | title = The ''Crocus sativus'' Compounds ''trans''-Crocin 4 and ''trans''-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models | journal = Frontiers in Neuroscience | volume = 13 | pages = 249 | date = 2019-03-26 | pmid = 30971876 | pmc = 6443833 | doi = 10.3389/fnins.2019.00249 | doi-access = free }}</ref>
=== Mood ===
Crocin displays possible antidepressant properties in mice<ref>{{cite journal | vauthors = Hosseinzadeh H, Jahanian Z | title = Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice | journal = Phytotherapy Research | volume = 24 | issue = 5 | pages = 726–730 | date = May 2010 | pmid = 19827024 | doi = 10.1002/ptr.3011 | s2cid = 38143210 }}</ref> and humans.<ref>{{cite journal | vauthors = Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F | title = Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816] | journal = BMC Complementary and Alternative Medicine | volume = 4 | pages = 12 | date = September 2004 | pmid = 15341662 | pmc = 517724 | doi = 10.1186/1472-6882-4-12 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati M, Khademi M, Foroutan-Tanha M, Ghayour-Mobarhan M, Hadizadeh F, Ferns G, Abbasi M | display-authors = 6 | title = The effects of crocin on the symptoms of depression in subjects with metabolic syndrome | journal = Advances in Clinical and Experimental Medicine | volume = 26 | issue = 6 | pages = 925–930 | date = September 2017 | pmid = 29068592 | doi = 10.17219/acem/62891 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Siddiqui SA, Ali Redha A, Snoeck ER, Singh S, Simal-Gandara J, Ibrahim SA, Jafari SM | title = Anti-Depressant Properties of Crocin Molecules in Saffron | journal = Molecules | volume = 27 | issue = 7 | pages = 2076 | date = March 2022 | pmid = 35408474 | pmc = 9000812 | doi = 10.3390/molecules27072076 | doi-access = free }}</ref>
=== Cancer ===
Crocin has also shown [[cytostasis|antiproliferative]] action against cancer cells ''[[in vitro]]''.<ref name="cancer1-Escribano">{{cite journal | vauthors = Escribano J, Alonso GL, Coca-Prados M, Fernandez JA | title = Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro | journal = Cancer Letters | volume = 100 | issue = 1–2 | pages = 23–30 | date = February 1996 | pmid = 8620447 | doi = 10.1016/0304-3835(95)04067-6 | doi-access = free }}</ref><ref name="cancer2-Chryssanthi">{{cite journal | vauthors = Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P | title = Inhibition of breast cancer cell proliferation by style constituents of different Crocus species | journal = Anticancer Research | volume = 27 | issue = 1A | pages = 357–362 | year = 2007 | pmid = 17352254 }}</ref><ref name="cancer3-Abdullaev">{{cite journal | vauthors = Abdullaev Jafarova F, Caballero-Ortega H, Riverón-Negrete L, Pereda-Miranda R, Rivera-Luna R, Manuel Hernández J, Pérez-López I, Espinosa-Aguirre JJ | display-authors = 6 | title = [In vitro evaluation of the chemopreventive potential of saffron] | journal = Revista de Investigacion Clinica | volume = 54 | issue = 5 | pages = 430–436 | year = 2002 | pmid = 12587418 }}</ref>  and  ''in vivo'' .<ref>{{cite journal | vauthors = Bakshi HA, Quinn GA, Nasef MM, Mishra V, Aljabali AA, El-Tanani M, Serrano-Aroca Á, Webba Da Silva M, McCarron PA, Tambuwala MM | display-authors = 6 | title = Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways | journal = Cells | volume = 11 | issue = 9 | pages = 1502 | date = April 2022 | pmid = 35563808 | pmc = 9104358 | doi = 10.3390/cells11091502 | doi-access = free }}</ref>
Crocin through the PI3K/AKT/mTOR, MAPK, VEGF, Wnt/β-catenin, and JAK-STAT suppression has antiproliferative properties. Also, the Nrf2 and p53 signaling pathway activation may be effective in the antiproliferative effect of crocin.<ref>{{cite journal | vauthors = Boozari M, Hosseinzadeh H | title = Crocin molecular signaling pathways at a glance: A comprehensive review | journal = Phytotherapy Research | pages = 3859–3884 | date = August 2022 | volume = 36 | issue = 10 | pmid = 35989419 | doi = 10.1002/ptr.7583 | s2cid = 251721130 }}</ref>
=== Behavior ===
[[Aphrodisiac]] properties of crocin in male rats has been observed at very high doses.<ref>{{cite journal | vauthors = Hosseinzadeh H, Ziaee T, Sadeghi A | title = The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats | journal = Phytomedicine | volume = 15 | issue = 6–7 | pages = 491–495 | date = June 2008 | pmid = 17962007 | doi = 10.1016/j.phymed.2007.09.020 }}</ref>
=== Retinal diseases===
Emerging evidence highlights the cytoprotective, antioxidative, and anti-inflammatory potential of crocin in [[retina|retinal]] tissue, which positions it as a promising candidate for enhancing vision and [[eye]] health. Nevertheless, it's important to note that the majority of research has primarily focused on animal models, and there remains a shortage of robust clinical data to firmly establish the benefits of crocin in addressing eye health and related diseases.<ref>{{cite journal |last1=Heydari |first1=Mojtaba |last2=Zare |first2=Mousa |last3=Badie |first3=Mohammad Reza |last4=Watson |first4=Ronald Ross |last5=Talebnejad |first5=Mohammad Reza |last6=Afarid |first6=Mehrdad |title=Crocin as a vision supplement |journal=Clinical & Experimental Optometry |date=April 2023 |volume=106 |issue=3 |pages=249–256 |doi=10.1080/08164622.2022.2039554 |pmid=35231199 |url=https://pubmed.ncbi.nlm.nih.gov/35231199/ |issn=1444-0938}}</ref>
== References ==
{{Reflist}}
== Bibliography ==
{{refbegin}}
* {{cite web |last1=NCBI |authorlink=NCBI|title=CID 5281233, Crocin |url=https://pubchem.ncbi.nlm.nih.gov/compound/Crocin |website=[[PubChem]] |publisher=[[United States National Library of Medicine|National Library of Medicine]] |location=Bethesda MD|date=2022|access-date=24 January 2022 }}
{{refend}}
== External links ==
*{{Commons category-inline}}
{{Carotenoids}}
[[Category:Carotenoid glycosides]]
[[Category:Dietary antioxidants]]
[[Category:Food colorings]]
[[Category:Saffron]]