The chemical structure of crocetin forms the central core ofcrocin, the compound responsible for the color ofsaffron. Crocetin is usually extracted commercially from gardenia fruit, due to the high cost of saffron.
A 2009 study involving 14 individuals indicated that oral administration of crocetin may decrease the effects of physical fatigue in healthy men.[6]
A 2010 pilot study investigated the effect of crocetin on sleep. The clinical trial comprised a double-blind, placebo-controlled, crossover trial of 21 healthy adult men with a mild sleep complaint. It concluded that crocetin may (p=0.025) contribute to improving the quality of sleep.[7]
In high concentrations, it has protective effects against retinal damagein vitro andin vivo.[8]
Thesodiumsalt of crocetin, transcrocetinate sodium (INN, also known as trans sodium crocetinate or TSC) is an experimental drug that increases the movement ofoxygen fromred blood cells intohypoxic (oxygen-starved) tissues.[9] Transcrocetinate sodium belongs to a group of substances known as bipolar trans carotenoid salts, which constitute a subclass ofoxygen diffusion-enhancing compounds.[10] Transcrocetinate sodium was one of the first such compounds discovered.[9][11]
Transcrocetinate sodium
Transcrocetinate sodium can be prepared by reactingsaffron withsodium hydroxide and extracting thesalt of the trans crocetinisomer from the solution.[11]John L. Gainer and colleagues have investigated the effects of transcrocetinate sodium in animal models.[11][12] They discovered that the drug could reverse the potentially fatal decrease in blood pressure produced by the loss of large volumes of blood in severehemorrhage, and thereby improve survival.[12]
Early investigations of transcrocetinate sodium suggested that it had potential applications inbattlefield medicine, specifically in treatment of the many combat casualties withhemorrhagic shock.[9][12] Additional studies, carried out in animal models, and in clinical trials in humans, indicated that transcrocetinate sodium might prove beneficial in the treatment of a variety of conditions associated withhypoxia andischemia (a lack of oxygen reaching the tissues, usually due to a disruption in the circulatory system), includingcancer,myocardial infarction (heart attack), andstroke.[9][10][13][14][15]
Transcrocetinate sodium has shown promise of effectiveness in restoring tissue oxygen levels and improving the ability to walk in a clinical trial of patients withperipheral artery disease (PAD)[14] in which reduced delivery of oxygen-rich blood to tissues can cause severe leg pain and impair mobility. The drug has also been under investigation in a clinical trial sponsored by drug developerDiffusion Pharmaceuticals for potential use as aradiosensitizer, increasing the susceptibility ofhypoxic cancer cells toradiation therapy, in patients with a form of brain cancer known asglioblastoma.[15] The drug is currently under investigation for its possible use in enhancing the oxygenation status ofCOVID-19 patients at risk for developing multiple organ failure due to severe respiratory distress.[16]
Similar to otheroxygen diffusion-enhancing compounds, transcrocetinate sodium appears to improve oxygenation in hypoxic tissues by exertinghydrophobic effects on water molecules inblood plasma and thereby increasing thehydrogen bonding between the water molecules.[17] This in turn causes the overall organization of water molecules in plasma to become more structured, which facilitates the diffusion of oxygen through plasma and promotes the movement of oxygen into tissues.[17][18][19]
^Umigai N, Murakami K, Ulit MV, et al. (May 2011). "The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration".Phytomedicine.18 (7):575–8.doi:10.1016/j.phymed.2010.10.019.PMID21112749.
^Mizuma H, Tanaka M, Nozaki S, Mizuno K, Tahara T, Ataka S, Sugino T, Shirai T, Kajimoto Y, Kuratsune H, Kajimoto O, Watanabe Y (March 2009). "Daily oral administration of crocetin attenuates physical fatigue in human subjects".Nutrition Research.29 (3):145–50.doi:10.1016/j.nutres.2009.02.003.PMID19358927.
^Kuratsune H, Umigai N, Takeno R, Kajimoto Y, Nakano T (September 2010). "Effect of crocetin fromGardenia jasminoides Ellis on sleep: a pilot study".Phytomedicine.17 (11):840–3.doi:10.1016/j.phymed.2010.03.025.PMID20537515.
^Yamauchi, M; Tsuruma, K; Imai, S; Nakanishi, T; Umigai, N; Shimazawa, M; Hara, H (2011). "Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase activity".European Journal of Pharmacology.650 (1):110–9.doi:10.1016/j.ejphar.2010.09.081.PMID20951131.
^abUS patent 8,206,751, Gainer J, "New Class of Therapeutics that Enhance Small Molecule Diffusion", issued 2009-04-30
^abcUS patent 6,060,511, Gainer J, "Trans-sodium crocetinate, methods of making and methods of use thereof", issued 2000-05-09
^abcGiassi L; et al. (2001). "Trans-Sodium Crocetinate Restores Blood Pressure, Heart Rate, and Plasma Lactate after Hemorrhagic Shock".Journal of Trauma-Injury Infection & Critical Care.51 (5):932–938.doi:10.1097/00005373-200111000-00018.PMID11706343.
^Lapchak P (2010). "Efficacy and safety profile of the carotenoid trans sodium crocetinate administered to rabbits following multiple infarct ischemic strokes: A combination therapy study with tissue plasminogen activator".Brain Research.1309:136–145.doi:10.1016/j.brainres.2009.10.067.PMID19891959.S2CID25369069.
^abStennett a; et al. (2006). "Trans sodium crocetinate and diffusion enhancement".The Journal of Physical Chemistry B.110 (37):18078–18080.doi:10.1021/jp064308+.PMID16970413.
^Laidig, K.E.; J.L. Gainer; V. Daggett (1998). "Altering Diffusivity in Biological Solutions through Modification of Solution Structure and Dynamics".Journal of the American Chemical Society.120 (36):9394–9395.doi:10.1021/ja981656j.
^Lautenschläger M, Lechtenberg M, Sendker J, Hensel A (2014). "Effective isolation protocol for secondary metabolites from saffron: semi-preparative scale preparation of crocin-1 and trans-crocetin".Fitoterapia.92:290–5.doi:10.1016/j.fitote.2013.11.014.PMID24321578.
^Lautenschläger M, Sendker J, Hüwel S, Galla HJ, Brandt S, Düfer M, Riehemann K, Hensel A (2015). "Intestinal formation of trans-crocetin from saffron extract (Crocus sativus L.) and in vitro permeation through intestinal and blood brain barrier".Phytomedicine.22 (1):36–44.doi:10.1016/j.phymed.2014.10.009.PMID25636868.
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