Crocin

Last updated
Crocin
Crocin.png
Names
IUPAC name
Bis[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] 8,8′-diapocarotene-8,8′-dioate
Systematic IUPAC name
Bis[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-({[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}methyl)oxan-2-yl] (2E,4E,6E,8E,10E,12E,14E)-2,6,11,15-tetramethylhexadeca-2,4,6,8,10,12,14-heptaenedioate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.050.783 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=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
    Key: SEBIKDIMAPSUBY-RTJKDTQDSA-N
  • 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
    Key: SEBIKDIMAPSUBY-RTJKDTQDBE
  • 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
Properties
C44H64O24
Molar mass 976.972 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Crocin is a carotenoid chemical compound that is found in the flowers of crocus and gardenia. [1] Its oxygen content also chemically makes it a xanthene. Crocin is the chemical primarily responsible for the color of saffron.

Contents

Chemically, crocin is the 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 °C. When dissolved in water, it forms an orange solution.

The term crocins may also refer to members of a series of related hydrophilic carotenoids that are either monoglycosyl or diglycosyl polyene esters of crocetin. [2] 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-gentiobiosyl) ester; it bears the systematic (IUPAC) name 8,8-diapo-8,8-carotenoic acid. [2] :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. [3]

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. [4] [5]

Antioxidant

Crocin has been shown to be an antioxidant, [6] [7] and neural protective agent. [8] [9] Crocin can reduce oxidative stress and ROS (Reactive Oxygen Species) through enhancement of gene expression of Nrf2, HO-1, and anti-oxidant enzymes, such as CAT, GSH, and SOD. [10] [2] [7]

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 and Parkinson's disease. [11]

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. [12]

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. [13]

Mood

Crocin displays possible antidepressant properties in mice [14] and humans. [15] [16] [17]

Cancer

Crocin has also shown antiproliferative action against cancer cells in vitro . [18] [19] [20] and in vivo . [21]

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. [22]

Behavior

Aphrodisiac properties of crocin in male rats has been observed at very high doses. [23]

Retinal diseases

Emerging evidence highlights the cytoprotective, antioxidative, and anti-inflammatory potential of crocin in 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. [24]

Related Research Articles

<span class="mw-page-title-main">Saffron</span> Spice made from crocus flowers

Saffron is a spice derived from the flower of Crocus sativus, commonly known as the "saffron crocus". The vivid crimson stigma and styles, called threads, are collected and dried for use mainly as a seasoning and colouring agent in food. Although some doubts remain on its origin, it is believed that saffron originated in Iran. However, Greece and Mesopotamia have also been suggested as the possible region of origin of this plant. The saffron crocus slowly propagated throughout much of Eurasia and was later brought to parts of North Africa, North America, and Oceania.

<i>Crocus</i> Genus of flowering plants in the family Iridaceae

Crocus is a genus of seasonal flowering plants in the family Iridaceae comprising about 100 species of perennials growing from corms. They are low growing plants, whose flower stems remain underground, that bear relatively large white, yellow, orange or purple flowers and then become dormant after flowering. Many are cultivated for their flowers, appearing in autumn, winter, or spring. The flowers close at night and in overcast weather conditions. The crocus has been known throughout recorded history, mainly as the source of saffron. Saffron is obtained from the dried stigma of Crocus sativus, an autumn-blooming species. It is valued as a spice and dyestuff, and is one of the most expensive spices in the world. Iran is the center of saffron production. Crocuses are native to woodland, scrub, and meadows from sea level to alpine tundra from the Mediterranean, through North Africa, central and southern Europe, the islands of the Aegean, the Middle East and across Central Asia to Xinjiang in western China. Crocuses may be propagated from seed or from daughter cormels formed on the corm, that eventually produce mature plants. They arrived in Europe from Turkey in the 16th century and became valued as an ornamental flowering plant.

<span class="mw-page-title-main">GSK-3</span> Class of enzymes

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS), GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways. In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction and bipolar disorder.

In organic chemistry, a dicarboxylic acid is an organic compound containing two carboxyl groups. The general molecular formula for dicarboxylic acids can be written as HO2C−R−CO2H, where R can be aliphatic or aromatic. In general, dicarboxylic acids show similar chemical behavior and reactivity to monocarboxylic acids.

<span class="mw-page-title-main">Neuroprotection</span> Relative preservation of neuronal structure and/or function

Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption. Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative stress, mitochondrial dysfunction, excitotoxicity, inflammatory changes, iron accumulation, and protein aggregation. Of these mechanisms, neuroprotective treatments often target oxidative stress and excitotoxicity—both of which are highly associated with CNS disorders. Not only can oxidative stress and excitotoxicity trigger neuron cell death but when combined they have synergistic effects that cause even more degradation than on their own. Thus limiting excitotoxicity and oxidative stress is a very important aspect of neuroprotection. Common neuroprotective treatments are glutamate antagonists and antioxidants, which aim to limit excitotoxicity and oxidative stress respectively.

<span class="mw-page-title-main">Zeaxanthin</span> Chemical compound

Zeaxanthin is one of the most common carotenoids in nature, and is used in the xanthophyll cycle. Synthesized in plants and some micro-organisms, it is the pigment that gives paprika, corn, saffron, goji (wolfberries), and many other plants and microbes their characteristic color.

<i>Crocus sativus</i> Species of plant, saffron crocus

Crocus sativus, commonly known as saffron crocus or autumn crocus, is a species of flowering plant in the iris family Iridaceae. A cormous autumn-flowering cultivated perennial, unknown in the wild, it is best known for the culinary use of its floral stigmas as the spice saffron. Human cultivation of saffron crocus and the trade and use of saffron have endured for more than 3,500 years and span different cultures, continents, and civilizations.

<span class="mw-page-title-main">Safranal</span> Chemical compound

Safranal is an organic compound isolated from saffron, the spice consisting of the stigmas of crocus flowers. It is the constituent primarily responsible for the aroma of saffron.

<span class="mw-page-title-main">Picrocrocin</span> Chemical compound

Picrocrocin is a monoterpene glycoside precursor of safranal. It is found in the spice saffron, which comes from the crocus flower. Picrocrocin has a bitter taste, and is the chemical most responsible for the taste of saffron.

<i>Crocus cartwrightianus</i> Species of flowering plant

Crocus cartwrightianus is a species of flowering plant in the family Iridaceae, native to mainland Greece and Crete. It is a cormous perennial growing to 5 cm (2 in). The flowers, in shades of lilac or white with purple veins and prominent red stigmas, appear with the leaves in autumn and winter.

<span class="mw-page-title-main">Crocetin</span> Carotenoid Chemical compound

Crocetin is a natural apocarotenoid dicarboxylic acid that is found in the crocus flower together with its glycoside, crocin, and Gardenia jasminoides fruits. It is also known as crocetic acid. It forms brick red crystals with a melting point of 285°C.

<span class="mw-page-title-main">Genistein</span> Chemical compound

Genistein (C15H10O5) is a naturally occurring compound that structurally belongs to a class of compounds known as isoflavones. It is described as an angiogenesis inhibitor and a phytoestrogen.

<span class="mw-page-title-main">Betulinic acid</span> Chemical compound

Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

Divicine (2,6-diamino-4,5-dihydroxypyrimidine) is an oxidant and a base with alkaloidal properties found in fava beans and Lathyrus sativus. It is an aglycone of vicine. A common derivative is the diacetate form (2,6-diamino-1,6-dihydro-4,5-pyrimidinedione).

<span class="mw-page-title-main">Valorphin</span> Chemical compound

Valorphin, also known as VV-hemorphin-5, is a naturally occurring, endogenous opioid heptapeptide of the hemorphin family with the amino acid sequence H-Val-Val-Tyr-Pro-Trp-Thr-Gln-OH (VVYPWTQ). It is produced in the body via proteolyic cleavage of residues 33-39 of the β-chain of hemoglobin. Valorphin binds preferentially to the μ-opioid receptor and produces effects such as analgesia and self-administration in animals. It also possesses cytotoxic and antiproliferative properties against tumor cells, the mediation of which, because they are reversed by naloxone, appears to be dependent on the opioid receptors.

An oxygen diffusion-enhancing compound is any substance that increases the availability of oxygen in body tissues by influencing the molecular structure of water in blood plasma and thereby promoting the movement (diffusion) of oxygen through plasma. Oxygen diffusion-enhancing compounds have shown promise in the treatment of conditions associated with hypoxia and ischemia. Such conditions include hemorrhagic shock, myocardial infarction, and stroke.

Crocetin glucosyltransferase is an enzyme with systematic name UDP-glucose:crocetin 8-O-D-glucosyltransferase. This enzyme catalyses the following chemical reaction

Saffron is one of the world's most expensive spices by weight due to its difficulty to harvest. Saffron consists of stigmas plucked from the vegetatively propagated and sterile Crocus sativus, known popularly as the saffron crocus. The resulting dried "threads" are distinguished by their bitter taste, hay-like fragrance, and slight metallic notes. The saffron crocus is unknown in the wild; its most likely precursor, Crocus cartwrightianus, originated in Crete or Central Asia; The saffron crocus is native to Southwest Asia, and is believed to have been first cultivated in Iran. Greece, Turkey, and Kashmir (India) have also been suggested as possible sites of origin.

"Saffron, for example, was once less regarded than it is today because the crocus from which it is extracted was not particularly mysterious. It flourished in European locations extending from Asia Minor, where it originated, to Saffron Walden in England, where it was naturalised. Only subsequently, when its labour-intensive cultivation became largely centred in Kashmir (India), did it seem sufficiently exotic to qualify as one of the most precious of spices."

<span class="mw-page-title-main">DCAF11</span> Protein-coding gene in the species Danio rerio

DDB1- and CUL4-associated factor 11 also known as WD Repeat Domain 23 (WDR23) is a protein that in humans is encoded by the DCAF11 gene.

References

  1. "Chemical Information". sun.ars-grin.gov. Archived from the original on 2004-11-08. Retrieved 2008-03-02.
  2. 1 2 3 Abdullaev FI (January 2002). "Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.)". Experimental Biology and Medicine. 227 (1): 20–25. doi:10.1177/153537020222700104. PMID   11788779. S2CID   40798771.
  3. Li N, Lin G, Kwan YW, Min ZD (July 1999). "Simultaneous quantification of five major biologically active ingredients of saffron by high-performance liquid chromatography". Journal of Chromatography A. 849 (2): 349–355. doi:10.1016/S0021-9673(99)00600-7. PMID   10457433.
  4. Popović-Djordjević JB, Stanković JS, Mihailović V, Akram M (2021-01-01). "Chapter 1 - Biochemistry and metabolism∗". In Galanakis CM (ed.). Chapter 1 - Biochemistry and metabolism. Academic Press. pp. 1–40. doi:10.1016/b978-0-12-821219-6.00001-4. ISBN   978-0-12-821219-6. S2CID   228897923 . Retrieved 2022-08-20.{{cite book}}: |journal= ignored (help)
  5. Lautenschläger M, Sendker J, Hüwel S, Galla HJ, Brandt S, Düfer M, et al. (January 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. PMID   25636868.
  6. Papandreou MA, Kanakis CD, Polissiou MG, Efthimiopoulos S, Cordopatis P, Margarity M, Lamari FN (November 2006). "Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents". Journal of Agricultural and Food Chemistry. 54 (23): 8762–8768. doi:10.1021/jf061932a. PMID   17090119.
  7. 1 2 Akhtari K; Hassanzadeh K; Fakhraei B; Fakhraei N; Hassanzadeh H; Zarei S A (2013). "A density functional theory study of the reactivity descriptors and antioxidant behavior of Crocin". Computational and Theoretical Chemistry. 1013: 123–129. doi:10.1016/j.comptc.2013.03.015.
  8. Ochiai T, Shimeno H, Mishima K, Iwasaki K, Fujiwara M, Tanaka H, et al. (April 2007). "Protective effects of carotenoids from saffron on neuronal injury in vitro and in vivo". Biochimica et Biophysica Acta (BBA) - General Subjects. 1770 (4): 578–584. doi:10.1016/j.bbagen.2006.11.012. PMID   17215084.
  9. Zheng YQ, Liu JX, Wang JN, Xu L (March 2007). "Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia". Brain Research. 1138: 86–94. doi:10.1016/j.brainres.2006.12.064. PMID   17274961. S2CID   25495517.
  10. Khoshandam A, Razavi BM, Hosseinzadeh H (July 2022). "Interaction of saffron and its constituents with Nrf2 signaling pathway: A review". Iranian Journal of Basic Medical Sciences. 25 (7): 789–798. doi:10.22038/ijbms.2022.61986.13719. ISSN   2008-3866. PMC   9392575 . PMID   36033950.
  11. Scuto M, Modafferi S, Rampulla F, Zimbone V, Tomasello M, Spano' S, et al. (July 2022). "Redox modulation of stress resilience by Crocus sativus L. for potential neuroprotective and anti-neuroinflammatory applications in brain disorders: From molecular basis to therapy". Mechanisms of Ageing and Development. 205: 111686. doi:10.1016/j.mad.2022.111686. PMID   35609733. S2CID   248950035.
  12. Mohammadzadeh L, Ghasemzadeh Rahbardar M, Razavi BM, Hosseinzadeh H (May 2022). "Crocin Protects Malathion-Induced Striatal Biochemical Deficits by Inhibiting Apoptosis and Increasing α-Synuclein in Rats' Striatum". Journal of Molecular Neuroscience. 72 (5): 983–993. doi:10.1007/s12031-022-01990-3. PMID   35274200. S2CID   247383603.
  13. Chalatsa I, Arvanitis DA, Koulakiotis NS, Giagini A, Skaltsounis AL, Papadopoulou-Daifoti Z, et al. (2019-03-26). "The Crocus sativus Compounds trans-Crocin 4 and trans-Crocetin Modulate the Amyloidogenic Pathway and Tau Misprocessing in Alzheimer Disease Neuronal Cell Culture Models". Frontiers in Neuroscience. 13: 249. doi: 10.3389/fnins.2019.00249 . PMC   6443833 . PMID   30971876.
  14. Hosseinzadeh H, Jahanian Z (May 2010). "Effect of Crocus sativus L. (saffron) stigma and its constituents, crocin and safranal, on morphine withdrawal syndrome in mice". Phytotherapy Research. 24 (5): 726–730. doi:10.1002/ptr.3011. PMID   19827024. S2CID   38143210.
  15. Akhondzadeh S, Fallah-Pour H, Afkham K, Jamshidi AH, Khalighi-Cigaroudi F (September 2004). "Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: a pilot double-blind randomized trial [ISRCTN45683816]". BMC Complementary and Alternative Medicine. 4: 12. doi: 10.1186/1472-6882-4-12 . PMC   517724 . PMID   15341662.
  16. Jam IN, Sahebkar AH, Eslami S, Mokhber N, Nosrati M, Khademi M, et al. (September 2017). "The effects of crocin on the symptoms of depression in subjects with metabolic syndrome". Advances in Clinical and Experimental Medicine. 26 (6): 925–930. doi: 10.17219/acem/62891 . PMID   29068592.
  17. Siddiqui SA, Ali Redha A, Snoeck ER, Singh S, Simal-Gandara J, Ibrahim SA, Jafari SM (March 2022). "Anti-Depressant Properties of Crocin Molecules in Saffron". Molecules. 27 (7): 2076. doi: 10.3390/molecules27072076 . PMC   9000812 . PMID   35408474.
  18. Escribano J, Alonso GL, Coca-Prados M, Fernandez JA (February 1996). "Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro". Cancer Letters. 100 (1–2): 23–30. doi: 10.1016/0304-3835(95)04067-6 . PMID   8620447.
  19. Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P (2007). "Inhibition of breast cancer cell proliferation by style constituents of different Crocus species". Anticancer Research. 27 (1A): 357–362. PMID   17352254.
  20. Abdullaev Jafarova F, Caballero-Ortega H, Riverón-Negrete L, Pereda-Miranda R, Rivera-Luna R, Manuel Hernández J, et al. (2002). "[In vitro evaluation of the chemopreventive potential of saffron]". Revista de Investigacion Clinica. 54 (5): 430–436. PMID   12587418.
  21. Bakshi HA, Quinn GA, Nasef MM, Mishra V, Aljabali AA, El-Tanani M, et al. (April 2022). "Crocin Inhibits Angiogenesis and Metastasis in Colon Cancer via TNF-α/NF-kB/VEGF Pathways". Cells. 11 (9): 1502. doi: 10.3390/cells11091502 . PMC   9104358 . PMID   35563808.
  22. Boozari M, Hosseinzadeh H (August 2022). "Crocin molecular signaling pathways at a glance: A comprehensive review". Phytotherapy Research. 36 (10): 3859–3884. doi:10.1002/ptr.7583. PMID   35989419. S2CID   251721130.
  23. Hosseinzadeh H, Ziaee T, Sadeghi A (June 2008). "The effect of saffron, Crocus sativus stigma, extract and its constituents, safranal and crocin on sexual behaviors in normal male rats". Phytomedicine. 15 (6–7): 491–495. doi:10.1016/j.phymed.2007.09.020. PMID   17962007.
  24. Heydari, Mojtaba; Zare, Mousa; Badie, Mohammad Reza; Watson, Ronald Ross; Talebnejad, Mohammad Reza; Afarid, Mehrdad (April 2023). "Crocin as a vision supplement". Clinical & Experimental Optometry. 106 (3): 249–256. doi:10.1080/08164622.2022.2039554. ISSN   1444-0938.

Bibliography