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Planta Med 2025; 91(06/07): 338-352
DOI: 10.1055/a-2538-5769
Reviews

Possibility and Potenzial Intervention Targets of Saffron Extract in the Treatment of Atopic Dermatitis: A Review

Huiyang Shi‡
2   Xiangya School of Medicine, Central South University, Changsha, P. R. China
,
Xuan Liu‡
1   Xiangya School of Public Health, Central South University, Changsha, P. R. China
,
Peiyi Zhao
2   Xiangya School of Medicine, Central South University, Changsha, P. R. China
,
Wei Huang
2   Xiangya School of Medicine, Central South University, Changsha, P. R. China
,
Hebin Wang
2   Xiangya School of Medicine, Central South University, Changsha, P. R. China
,
Heying Jin
2   Xiangya School of Medicine, Central South University, Changsha, P. R. China
,
Junyou Zhu
3   Department of Burn, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P. R. China
,
Jianwu Wang
1   Xiangya School of Public Health, Central South University, Changsha, P. R. China
,
Tianjiao Li
1   Xiangya School of Public Health, Central South University, Changsha, P. R. China
› Author Affiliations
The authors are grateful to the National Science Foundation of China (Grant No. 82102332), the Natural Science Foundation of Hunan Province (Grant Nos. 2022JJ40667 and 2022JJ30785), the Graduate Student Independent Exploration and Innovation Program of Central South University (1053320241380), the China International College Studentsʼ Innovation Competition (CXPY2024437), and the Natural Science Foundation of Changsha (Grant Nos. kq2202128 and kq2202078).
› Further Information
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Abstract

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disorder characterized by dry skin, eczema-like lesions, and severe itching. The multifaceted etiology of AD, which is not yet fully understood, includes genetic predispositions, immune dysfunctions(such as an impaired skin barrier and abnormal immune regulation), imbalances in the skin microbiota, and environmental factors, among others. In the field of AD treatment, the combination of traditional Chinese medicine and modern medicine is becoming an emerging trend. Given the potenzial side effects and reduced efficacy of conventional therapeutic drugs, Chinese herbal medicines offer patients new treatment options because of their unique efficacy and low toxicity. Some saffron extracts derived from saffron and gardenia, such as crocin, crocetin, and safranal, have shown promising potenzial in the treatment of AD. These natural ingredients not only possess anti-inflammatory and immunomodulatory properties similar to those of traditional Chinese medicines but also demonstrate excellent effects in promoting the repair of damaged skin barriers. Therefore, this article reviews the therapeutic potenzial of saffron extract in the treatment of AD, with a special focus on its mechanisms and potenzial interventions, while emphasizing the importance of herbal medicines as alternatives to traditional treatments, providing AD patients with safer and more effective treatment options.

Keywords

Atopic dermatitis - saffron - Iridaceae - Gardenia - Rubiaceae - crocin - crocetin - safranal


Publication History

Received: 01 October 2024

Accepted after revision: 29 January 2025

Accepted Manuscript online:
13 February 2025

Article published online:
20 March 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Yao X, Song ZQ, Li W, Liang YS, Zhao Y, Cao H, Chen T, Chen X, Feng AP, Geng SM, Gu H, Guo SP, He YL, Kuang YH, Li CY, Li XH, Li ZX, Liang JQ, Liu HY, Liu LL, Liu YM, Liu Z, Long H, Lu QJ, Lu Y, Luo XQ, Lv XY, Ma L, Shen Z, Shi X, Shi ZX, Su XY, Sun Q, Tang JP, Wang AX, Wang HP, Wang JQ, Wang MY, Wang ZX, Xia YM, Xiao T, Xie ZQ, Xing H, Xiong Y, Xu ZG, Yang B, Yao ZR, Yu JB, Yu N, Zeng K, Zhang JZ, Zhang JL, Zhao H, Zhao ZT, Zhu W, Zhu YH, Zou Y. Guidelines for diagnosis and treatment of atopic dermatitis in China (2020). Int J Dermatol Venereol 2021; 4: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 2 Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet (London, England) 2020; 396: 345-360
    CrossrefPubMedSearch in Google Scholar
  • 3 Czarnowicki T, He H, Krueger JG, Guttman Yassky E. Atopic dermatitis endotypes and implications for targeted therapeutics. J Allergy Clin Immunol 2019; 143: 1-11
    CrossrefPubMedSearch in Google Scholar
  • 4 Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers 2018; 4: 1
    CrossrefPubMedSearch in Google Scholar
  • 5 Ravnborg N, Ambikaibalan D, Agnihotri G, Price S, Rastogi S, Patel KR, Singam V, Andersen Y, Halling AS, Silverberg JI, Egeberg A, Thyssen JP. Prevalence of asthma in patients with atopic dermatitis: A systematic review and meta-analysis. J Am Acad Dermatol 2021; 84: 471-478
    CrossrefPubMedSearch in Google Scholar
  • 6 Cai X, Sun X, Liu L, Zhou Y, Hong S, Wang J, Chen J, Zhang M, Wang C, Lin N, Li S, Xu R, Li X. Efficacy and safety of Chinese herbal medicine for atopic dermatitis: Evidence from eight high-quality randomized placebo-controlled trials. Front Pharmacol 2022; 13: 927304
    CrossrefPubMedSearch in Google Scholar
  • 7 Zhang R, Zhang H, Shao S, Shen Y, Xiao F, Sun J, Piao S, Zhao D, Li G, Yan M. Compound traditional Chinese medicine dermatitis ointment ameliorates inflammatory responses and dysregulation of itch-related molecules in atopic dermatitis. Chin Med 2022; 17: 3
    CrossrefPubMedSearch in Google Scholar
  • 8 Zhang Q, Xie J, Li G, Wang F, Lin J, Yang M, Du A, Zhang D, Han L. Psoriasis treatment using indigo naturalis: Progress and strategy. J Ethnopharmacol 2022; 297: 115522
    CrossrefPubMedSearch in Google Scholar
  • 9 Min GY, Kim JH, Kim TI, Cho WK, Yang JH, Ma JY. Indigo Pulverata levis (Chung-Dae, Persicaria tinctoria) alleviates atopic dermatitis-like inflammatory responses In vivo and In vitro. Int J Mol Sci 2022; 23: 553
    CrossrefPubMedSearch in Google Scholar
  • 10 Gresta F, Lombardo GM, Siracusa L, Ruberto G. Saffron, an alternative crop for sustainable agricultural systems. A review. Agron Sustainable Dev 2008; 28: 95-112
    CrossrefPubMedSearch in Google Scholar
  • 11 Ríos JL, Recio MC, Giner RM, Máñez S. An update review of saffron and its active constituents. Phytother Res 1996; 10: 189-193
    CrossrefPubMedSearch in Google Scholar
  • 12 Fernandez JA. Biology, biotechnology and biomedicine of saffron. Biol Biotechnol Biomed Saffron 2004; 127-159
    PubMedSearch in Google Scholar
  • 13 El Midaoui A, Ghzaiel I, Vervandier-Fasseur D, Ksila M, Zarrouk A, Nury T, Khallouki F, El Hessni A, Ibrahimi SO, Latruffe N, Couture R, Kharoubi O, Brahmi F, Hammami S, Masmoudi-Kouki O, Hammami M, Ghrairi T, Vejux A, Lizard G. Saffron (Crocus sativus L.): A source of nutrients for health and for the treatment of neuropsychiatric and age-related diseases. Nutrients 2022; 14: 597
    CrossrefPubMedSearch in Google Scholar
  • 14 Chrysanthou A, Pouliou E, Kyriakoudi A, Tsimidou MZ. Sensory threshold studies of picrocrocin, the major bitter compound of saffron. J Food Sci 2016; 81: S189-198
    CrossrefPubMedSearch in Google Scholar
  • 15 Chen L, Li M, Yang Z, Tao W, Wang P, Tian X, Li X, Wang W. Gardenia jasminoides ellis: Ethnopharmacology, phytochemistry, and pharmacological and industrial applications of an important traditional chinese medicine. J Ethnopharmacol 2020; 257: 112829
    CrossrefPubMedSearch in Google Scholar
  • 16 Liu Y, Wang Z, Zhang J. Dietary Chinese Herbs: Chemistry, Pharmacology and Clinical Evidence. Vienna: Springer Vienna; 2015
    Search in Google Scholar
  • 17 Abdul Wahab UH, Awad ZJ. Isolation and characterization of iridoid glycoside (Gardenoside) present in the leaves of gardenia jasminoides J.ellis cultivated in Iraq. Iraqi J Pharm Sci 2017; 24: 40-48
    CrossrefPubMedSearch in Google Scholar
  • 18 Wen L, Fan C, Zhao X, Cao X. Rapid extraction of bioactive compounds from gardenia fruit using new and recyclable deep eutectic solvents. J Sep Sci 2023; 46: 2300163
    CrossrefPubMedSearch in Google Scholar
  • 19 Chen Y, Zhang H, Tian X, Zhao C, Cai L, Liu Y, Jia L, Yin HX, Chen C. Antioxidant potential of crocins and ethanol extracts of gardenia jasminoides ELLIS and crocus sativus L.: A relationship investigation between antioxidant activity and crocin contents. Food Chem 2008; 109: 484-492
    CrossrefPubMedSearch in Google Scholar
  • 20 Hong IK, Jeon H, Lee SB. Extraction of natural dye from Gardenia and chromaticity analysis according to chi parameter. J Ind Eng Chem 2015; 24: 326-332
    CrossrefPubMedSearch in Google Scholar
  • 21 Ali A, Yu L, Kousar S, Khalid W, Maqbool Z, Aziz A, Arshad MS, Aadil RM, Trif M, Riaz S, Shaukat H, Manzoor MF, Qin H. Crocin: Functional characteristics, extraction, food applications and efficacy against brain related disorders. Front Nutr 2022; 9: 1009807
    CrossrefPubMedSearch in Google Scholar
  • 22 Bakshi RA, Sodhi NS, Wani IA, Khan ZS, Dhillon B, Gani A. Bioactive constituents of saffron plant: Extraction, encapsulation and their food and pharmaceutical applications. Appl Food Res 2022; 2: 100076
    CrossrefPubMedSearch in Google Scholar
  • 23 Kalantar M, Kalantari H, Goudarzi M, Khorsandi L, Bakhit S, Kalantar H. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacol Rep 2019; 71: 746-752
    CrossrefPubMedSearch in Google Scholar
  • 24 Wang Y, Wang Q, Yu W, Du H. Crocin attenuates oxidative stress and myocardial infarction injury in rats. Int Heart J 2018; 59: 387-393
    CrossrefPubMedSearch in Google Scholar
  • 25 Mykhailenko O, Bezruk I, Ivanauskas L, Georgiyants V. Comparative analysis of apocarotenoids and phenolic constituents of crocus sativus stigmas from 11 countries: Ecological impact. Arch Pharm 2022; 355: e2100468
    CrossrefPubMedSearch in Google Scholar
  • 26 Khajuria DK, Asad M, Asdaq SMB, Kumar P. The potency of crocus sativus (saffron) and its constituent crocin as an immunomodulator in animals. Lat Am J Pharm 2010; 29: 713-718
    PubMedSearch in Google Scholar
  • 27 Finley JW, Gao S. A perspective on crocus sativus L. (saffron) constituent crocin: A potent water-soluble antioxidant and potential therapy for Alzheimerʼs disease. J Agric Food Chem 2017; 65: 1005-1020
    CrossrefPubMedSearch in Google Scholar
  • 28 Samaha MM, Said E, Salem HA. A comparative study of the role of crocin and sitagliptin in attenuation of STZ-induced diabetes mellitus and the associated inflammatory and apoptotic changes in pancreatic β-islets. Environ Toxicol Pharmacol 2019; 72: 103238
    CrossrefPubMedSearch in Google Scholar
  • 29 Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018; 101: 174-180
    CrossrefPubMedSearch in Google Scholar
  • 30 Baradaran Rahim V, Khammar MT, Rakhshandeh H, Samzadeh-Kermani A, Hosseini A, Askari VR. Crocin protects cardiomyocytes against LPS-induced inflammation. Pharmacol Rep 2019; 71: 1228-1234
    CrossrefPubMedSearch in Google Scholar
  • 31 Xie X, Zhang M, Sun L, Wang T, Zhu Z, Shu R, Wu F, Li Z. Crocin-I protects against high-fat diet-induced obesity via modulation of gut microbiota and intestinal inflammation in mice. Front Pharmacol 2022; 13: 894089
    CrossrefPubMedSearch in Google Scholar
  • 32 Nedoszytko B, Reszka E, Gutowska-Owsiak D, Trzeciak M, Lange M, Jarczak J, Niedoszytko M, Jablonska E, Romantowski J, Strapagiel D, Skokowski J, Siekierzycka A, Nowicki RJ, Dobrucki IT, Zaryczańska A, Kalinowski L. Genetic and epigenetic aspects of atopic dermatitis. Int J Mol Sci 2020; 21: 6484
    CrossrefPubMedSearch in Google Scholar
  • 33 Moosbrugger-Martinz V, Leprince C, Méchin MC, Simon M, Blunder S, Gruber R, Dubrac S. Revisiting the roles of filaggrin in atopic dermatitis. Int J Mol Sci 2022; 23: 5318
    CrossrefPubMedSearch in Google Scholar
  • 34 Hashimoto-Hachiya A, Tsuji G, Murai M, Yan X, Furue M. Upregulation of FLG, LOR, and IVL expression by rhodiola crenulata root extract via aryl hydrocarbon receptor: Differential involvement of OVOL1. Int J Mol Sci 2018; 19: 1654
    CrossrefPubMedSearch in Google Scholar
  • 35 Morizane S, Ouchida M, Sunagawa K, Sugimoto S, Kobashi M, Sugihara S, Nomura H, Tsuji K, Sato A, Miura Y, Hattori H, Tada K, Huh WK, Seno A, Iwatsuki K. Analysis of all 34 exons of the SPINK5 gene in Japanese atopic dermatitis patients. Acta Med Okayama 2018; 72: 275-282
    PubMedSearch in Google Scholar
  • 36 Emrick JJ, Mathur A, Wei J, Gracheva EO, Gronert K, Rosenblum MD, Julius D. Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch. Proc Natl Acad Sci U S A 2018; 115: E12091-E12100
    CrossrefPubMedSearch in Google Scholar
  • 37 Furue M. Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic implications in atopic dermatitis. Int J Mol Sci 2020; 21: 5382
    CrossrefPubMedSearch in Google Scholar
  • 38 Hussain M, Borcard L, Walsh KP, Pena Rodriguez M, Mueller C, Kim BS, Kubo M, Artis D, Noti M. Basophil-derived IL-4 promotes epicutaneous antigen sensitization concomitant with the development of food allergy. J Allergy Clin Immunol 2018; 141: 223-234.e5
    CrossrefPubMedSearch in Google Scholar
  • 39 Murdaca G, Greco M, Tonacci A, Negrini S, Borro M, Puppo F, Gangemi S. IL-33/IL-31 axis in immune-mediated and allergic diseases. Int J Mol Sci 2019; 20: 5856
    CrossrefPubMedSearch in Google Scholar
  • 40 Zhang YY, Wang AX, Xu L, Shen N, Zhu J, Tu CX. Characteristics of peripheral blood CD4+CD25+ regulatory T cells and related cytokines in severe atopic dermatitis. Eur J Dermatol 2016; 26: 240-246
    CrossrefPubMedSearch in Google Scholar
  • 41 Lee Y, Choi HK, Nʼdeh KPU, Choi YJ, Fan M, Kim EK, Chung KH, An AJH. Inhibitory effect of centella asiatica extract on DNCB-induced atopic dermatitis in HaCaT cells and BALB/c mice. Nutrients 2020; 12: 411
    CrossrefPubMedSearch in Google Scholar
  • 42 Yoon J, Leyva-Castillo JM, Wang G, Galand C, Oyoshi MK, Kumar L, Hoff S, He R, Chervonsky A, Oppenheim JJ, Kuchroo VK, Van den Brink MRM, Malefyt RDW, Tessier PA, Fuhlbrigge R, Rosenstiel P, Terhorst C, Murphy G, Geha RS. IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization. J Exp Med 2016; 213: 2147-2166
    CrossrefPubMedSearch in Google Scholar
  • 43 Weidinger S, Klopp N, Rummler L, Wagenpfeil S, Novak N, Baurecht HJ, Groer W, Darsow U, Heinrich J, Gauger A, Schafer T, Jakob T, Behrendt H, Wichmann HE, Ring J, Illig T. Association of NOD1 polymorphisms with atopic eczema and related phenotypes. J Allergy Clin Immunol 2005; 116: 177-184
    CrossrefPubMedSearch in Google Scholar
  • 44 Wong CK, Chu IMT, Hon KL, Tsang MSM, Lam CWK. Aberrant expression of bacterial pattern recognition receptor NOD2 of basophils and microbicidal peptides in atopic dermatitis. Molecules (Basel, Switzerland) 2016; 21: 471
    CrossrefPubMedSearch in Google Scholar
  • 45 Sun L, Liu W, Zhang LJ. The role of toll-like receptors in skin host defense, psoriasis, and atopic dermatitis. J Immunol Res 2019; 2019: 1824624
    PubMedSearch in Google Scholar
  • 46 Yoon NY, Wang HY, Jun M, Jung M, Kim DH, Lee NR, Hong KW, Seo SJ, Choi E, Lee J, Lee H, Choi EH. Simultaneous detection of barrier- and immune-related gene variations in patients with atopic dermatitis by reverse blot hybridization assay. Clin Exp Dermatol 2018; 43: 430-436
    CrossrefPubMedSearch in Google Scholar
  • 47 Kumar D, Puan KJ, Andiappan AK, Lee B, Westerlaken GHA, Haase D, Melchiotti R, Li Z, Yusof N, Lum J, Koh G, Foo S, Yeong J, Alves AC, Pekkanen J, Sun LD, Irwanto A, Fairfax BP, Naranbhai V, Common JEA, Tang M, Chuang CK, Jarvelin MR, Knight JC, Zhang X, Chew FT, Prabhakar S, Jianjun L, Wang DY, Zolezzi F, Poidinger M, Lane EB, Meyaard L, Rötzschke O. A functional SNP associated with atopic dermatitis controls cell type-specific methylation of the VSTM1 gene locus. Genome Med 2017; 9: 18
    CrossrefPubMedSearch in Google Scholar
  • 48 Liang Y, Wang P, Zhao M, Liang G, Yin H, Zhang G, Wen H, Lu Q. Demethylation of the FCER1 G promoter leads to FcεRI overexpression on monocytes of patients with atopic dermatitis. Allergy 2012; 67: 424-430
    CrossrefPubMedSearch in Google Scholar
  • 49 Lee SY, Hong SH, Kim HI, Ku JM, Choi YJ, Kim MJ, Ko SG. Paeonia lactiflora pallas extract alleviates antibiotics and DNCB-induced atopic dermatitis symptoms by suppressing inflammation and changing the gut microbiota composition in mice. Biomed Pharmacother 2022; 154: 113574
    CrossrefPubMedSearch in Google Scholar
  • 50 Robertson ED, Weir L, Romanowska M, Leigh IM, Panteleyev AA. ARNT controls the expression of epidermal differentiation genes through HDAC- and EGFR-dependent pathways. J Cell Sci 2012; 125: 3320-3332
    PubMedSearch in Google Scholar
  • 51 Bergallo M, Accorinti M, Galliano I, Coppo P, Montanari P, Quaglino P, Savino F. Expression of miRNA 155, FOXP3 and ROR gamma, in children with moderate and severe atopic dermatitis. G Ital Dermatol Venereol 2020; 155: 168-172
    CrossrefPubMedSearch in Google Scholar
  • 52 Meng L, Li M, Gao Z, Ren H, Chen J, Liu X, Cai Q, Jiang L, Ren X, Yu Q, Chen J, Yang L. Possible role of hsa-miR-194–5 p, via regulation of HS3ST2, in the pathogenesis of atopic dermatitis in children. Eur J Dermatol 2019; 29: 603-613
    CrossrefPubMedSearch in Google Scholar
  • 53 Vaher H, Runnel T, Urgard E, Aab A, Carreras Badosa G, Maslovskaja J, Abram K, Raam L, Kaldvee B, Annilo T, Tkaczyk ER, Maimets T, Akdis CA, Kingo K, Rebane A. miR-10a-5 p is increased in atopic dermatitis and has capacity to inhibit keratinocyte proliferation. Allergy 2019; 74: 2146-2156
    CrossrefPubMedSearch in Google Scholar
  • 54 Jia HZ, Liu SL, Zou YF, Chen XF, Yu L, Wan J, Zhang HY, Chen Q, Xiong Y, Yu B, Zhang W. MicroRNA-223 is involved in the pathogenesis of atopic dermatitis by affecting histamine-N-methyltransferase. Cell Mol Biol (Noisy-Le-Gd. Fr ) 2018; 64: 103-107
    PubMedSearch in Google Scholar
  • 55 Sweeney A, Sampath V, Nadeau KC. Early intervention of atopic dermatitis as a preventive strategy for progression of food allergy. Allergy Asthma Clin Immunol 2021; 17: 30
    CrossrefPubMedSearch in Google Scholar
  • 56 Leung DYM, Berdyshev E, Goleva E. Cutaneous barrier dysfunction in allergic diseases. J Allergy Clin Immunol 2020; 145: 1485-1497
    CrossrefPubMedSearch in Google Scholar
  • 57 Irvine AD, McLean WHI, Leung DYM. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med 2011; 365: 1315-1327
    CrossrefPubMedSearch in Google Scholar
  • 58 Edslev SM, Agner T, Andersen PS. Skin microbiome in atopic dermatitis. Acta Dermato-Venereologica 2020; 100: adv00164
    CrossrefPubMedSearch in Google Scholar
  • 59 Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol 2011; 41: 298-310
    CrossrefPubMedSearch in Google Scholar
  • 60 Elser B, Lohoff M, Kock S, Giaisi M, Kirchhoff S, Krammer PH, Li-Weber M. IFN-γ represses IL-4 expression via IRF-1 and IRF-2. Immunity 2002; 17: 703-712
    CrossrefPubMedSearch in Google Scholar
  • 61 Zheng W, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 1997; 89: 587-596
    CrossrefPubMedSearch in Google Scholar
  • 62 Boguniewicz M, Leung DYM. Atopic dermatitis: A disease of altered skin barrier and immune dysregulation. Immunol Rev 2011; 242: 233-246
    CrossrefPubMedSearch in Google Scholar
  • 63 Chu H, Park KH, Kim SM, Lee JH, Park JW, Lee KH, Park CO. Allergen-specific immunotherapy for patients with atopic dermatitis sensitized to animal dander. Immun Inflammation Dis 2020; 8: 165-169
    CrossrefPubMedSearch in Google Scholar
  • 64 Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG, Pérez-Herrera LC, Chu AWL, Ceccaci R, Acosta-Madiedo AS, Wen A, Moreno-López S, MacDonald M, Barrios M, Chu X, Islam N, Gao Y, Wong MM, Couban R, Garcia E, Chapman E, Oykhman P, Chen L, Winders T, Asiniwasis RN, Boguniewicz M, De Benedetto A, Ellison K, Frazier WT, Greenhawt M, Huynh J, Kim E, LeBovidge J, Lind ML, Lio P, Martin SA, OʼBrien M, Ong PY, Silverberg JI, Spergel J, Wang J, Wheeler KE, Schneider L, Chu DK. Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms. J Allergy Clin Immunol 2023; 151: 147-158
    CrossrefPubMedSearch in Google Scholar
  • 65 Chong AC, Chwa WJ, Ong PY. Aeroallergens in atopic dermatitis and chronic urticaria. Curr Allergy Asthma Rep 2022; 22: 67-75
    CrossrefPubMedSearch in Google Scholar
  • 66 Fadadu RP, Abuabara K, Balmes JR, Hanifin JM, Wei ML. Air pollution and atopic dermatitis, from molecular mechanisms to population-level evidence: A review. Int J Environ Res Public Health 2023; 20: 2526
    CrossrefPubMedSearch in Google Scholar
  • 67 Hui-Beckman JW, Goleva E, Leung DYM, Kim BE. The impact of temperature on the skin barrier and atopic dermatitis. Ann Allergy Asthma Immunol 2023; 131: 713-719
    CrossrefPubMedSearch in Google Scholar
  • 68 Arck P, Paus R. From the brain-skin connection: The neuroendocrine-immune misalliance of stress and itch. Neuroimmunomodulation 2006; 13: 347-356
    CrossrefPubMedSearch in Google Scholar
  • 69 Pondeljak N, Lugović-Mihić L. Stress-induced interaction of skin immune cells, hormones, and neurotransmitters. Clin Ther 2020; 42: 757-770
    CrossrefPubMedSearch in Google Scholar
  • 70 Slominski AT, Slominski RM, Raman C, Chen JY, Athar M, Elmets C. Neuroendocrine signaling in the skin with a special focus on the epidermal neuropeptides. Am J Physiol Cell Physiol 2022; 323: C1757-C1776
    CrossrefPubMedSearch in Google Scholar
  • 71 Li B, Wu YR, Li L, Liu Y, Yan ZY. A novel based-network strategy to identify phytochemicals from radix salviae miltiorrhizae (danshen) for treating alzheimerʼs disease. Molecules 2022; 27: 4463
    CrossrefPubMedSearch in Google Scholar
  • 72 Byrd AL, Belkaid Y, Segre JA. The human skin microbiome. Nat Rev Microbiol 2018; 16: 143-155
    CrossrefPubMedSearch in Google Scholar
  • 73 Di Domenico EG, Cavallo I, Capitanio B, Ascenzioni F, Pimpinelli F, Morrone A, Ensoli F. Staphylococcus aureus and the cutaneous microbiota biofilms in the pathogenesis of atopic dermatitis. Microorganisms 2019; 7: 301
    CrossrefPubMedSearch in Google Scholar
  • 74 Koh LF, Ong RY, Common JE. Skin microbiome of atopic dermatitis. Allergol Int 2022; 71: 31-39
    CrossrefPubMedSearch in Google Scholar
  • 75 Kong HH, Segre JA. The molecular revolution in cutaneous biology: Investigating the skin microbiome. J Invest Dermatol 2017; 137: e119-e122
    CrossrefPubMedSearch in Google Scholar
  • 76 Kim JE, Kim HS. Microbiome of the skin and gut in atopic dermatitis (AD): Understanding the pathophysiology and finding novel management strategies. J Clin Med 2019; 8: 444
    CrossrefPubMedSearch in Google Scholar
  • 77 Iwamoto K, Moriwaki M, Miyake R, Hide M. Staphylococcus aureus in atopic dermatitis: Strain-specific cell wall proteins and skin immunity. Allergol Int 2019; 68: 309-315
    CrossrefPubMedSearch in Google Scholar
  • 78 Climent E, Martinez-Blanch JF, Llobregat L, Ruzafa-Costas B, Carrión-Gutiérrez MÁ, Ramírez-Boscá A, Prieto-Merino D, Genovés S, Codoñer FM, Ramón D, Chenoll E, Navarro-López V. Changes in gut microbiota correlates with response to treatment with probiotics in patients with atopic dermatitis. A post hoc analysis of a clinical trial. Microorganisms 2021; 9: 854
    CrossrefPubMedSearch in Google Scholar
  • 79 Paller AS, Kong HH, Seed P, Naik S, Scharschmidt TC, Gallo RL, Luger T, Irvine AD. The microbiome in patients with atopic dermatitis. J Allergy Clin Immunol 2019; 143: 26-35
    CrossrefPubMedSearch in Google Scholar
  • 80 Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M. Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001; 108: 516-520
    CrossrefPubMedSearch in Google Scholar
  • 81 Fang Z, Li L, Zhang H, Zhao J, Lu W, Chen W. Gut microbiota, probiotics, and their interactions in prevention and treatment of atopic dermatitis: A review. Front Immunol 2021; 12: 720393
    CrossrefPubMedSearch in Google Scholar
  • 82 Lee MJ, Kang MJ, Lee SY, Lee E, Kim K, Won S, Suh DI, Kim KW, Sheen YH, Ahn K, Kim BS, Hong SJ. Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type. J Allergy Clin Immunol 2018; 141: 1310-1319
    CrossrefPubMedSearch in Google Scholar
  • 83 Melli LCFL, do Carmo-Rodrigues MS, Araújo-Filho HB, Mello CS, Tahan S, Pignatari ACC, Solé D, de Morais MB. Gut microbiota of children with atopic dermatitis: Controlled study in the metropolitan region of São Paulo, Brazil. Allergol Immunopathol (Madr) 2020; 48: 107-115
    CrossrefPubMedSearch in Google Scholar
  • 84 Shi J, Wang Y, Cheng L, Wang J, Raghavan V. Gut microbiome modulation by probiotics, prebiotics, synbiotics and postbiotics: A novel strategy in food allergy prevention and treatment. Crit Rev Food Sci Nutr 2024; 64: 5984-6000
    CrossrefPubMedSearch in Google Scholar
  • 85 Rachid R, Chatila TA. The role of the gut microbiota in food allergy. Curr Opin Pediatr 2016; 28: 748-753
    CrossrefPubMedSearch in Google Scholar
  • 86 Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 2009; 9: 313-323
    CrossrefPubMedSearch in Google Scholar
  • 87 Nowak-Wegrzyn A, Szajewska H, Lack G. Food allergy and the gut. Nat Rev Gastroenterol Hepatol 2017; 14: 241-257
    CrossrefPubMedSearch in Google Scholar
  • 88 Kyriakoudi A, Chrysanthou A, Mantzouridou F, Tsimidou MZ. Revisiting extraction of bioactive apocarotenoids from crocus sativus L. dry stigmas (saffron). Anal Chim Acta 2012; 755: 77-85
    CrossrefPubMedSearch in Google Scholar
  • 89 Mollafilabi A. Experimental findings of production and echo physiological aspects of saffron (crocus sativus l.). Acta Horticulturae 2004; 650: 195-200
    CrossrefPubMedSearch in Google Scholar
  • 90 Mohajeri SA, Hosseinzadeh H, Keyhanfar F, Aghamohammadian J. Extraction of crocin from saffron (crocus sativus) using molecularly imprinted polymer solid-phase extraction. J Sep Sci 2010; 33: 2302-2309
    CrossrefPubMedSearch in Google Scholar
  • 91 Sarfarazi M, Jafari SM, Rajabzadeh G, Galanakis CM. Evaluation of microwave-assisted extraction technology for separation of bioactive components of saffron (crocus sativus L.). Ind Crops Prod 2020; 145: 111978
    CrossrefPubMedSearch in Google Scholar
  • 92 Goleroudbary MG, Ghoreishi SM. Response surface optimization of safranal and crocin extraction from crocus sativus L. via supercritical fluid technology. J Supercrit Fluids 2016; 108: 136-144
    CrossrefPubMedSearch in Google Scholar
  • 93 Sarfarazi M, Jafari SM, Rajabzadeh G, Feizi J. Development of an environmentally-friendly solvent-free extraction of saffron bioactives using subcritical water. LWT 2019; 114: 108428
    CrossrefPubMedSearch in Google Scholar
  • 94 Maggi L, Sánchez AM, Carmona M, Kanakis CD, Anastasaki E, Tarantilis PA, Polissiou MG, Alonso GL. Rapid determination of safranal in the quality control of saffron spice (crocus sativus L.). Food Chem 2011; 127: 369-373
    CrossrefPubMedSearch in Google Scholar
  • 95 Nerome H, Ito M, Machmudah S, Wahyudiono D, Kanda H, Goto M. Extraction of phytochemicals from saffron by supercritical carbon dioxide with water and methanol as entrainer. J Supercrit Fluids 2016; 107: 377-383
    CrossrefPubMedSearch in Google Scholar
  • 96 Pourzaki A, Mirzaee H, Hemmati Kakhki A. Using pulsed electric field for improvement of components extraction of saffron (Crocus sativus) stigma and its pomace. Extraction of saffron components by Pef. J Food Process Preserv 2013; 37: 1008-1013
    CrossrefPubMedSearch in Google Scholar
  • 97 Yang B, Gao Y, Liu X, Li Y, Zhao J. Adsorption characteristics of crocin in the extract of gardenia fruits (gardenia jasminoides ellis) on macroporous resins. J Food Process Eng 2009; 32: 35-52
    CrossrefPubMedSearch in Google Scholar
  • 98 Feng J, He X, Zhou S, Peng F, Liu J, Hao L, Li H, Ao G, Yang S. Preparative separation of crocins and geniposide simultaneously from gardenia fruits using macroporous resin and reversed-phase chromatography. J Sep Sci 2014; 37: 314-322
    CrossrefPubMedSearch in Google Scholar
  • 99 Huang H, Zhu Y, Fu X, Zou Y, Li Q, Luo Z. Integrated natural deep eutectic solvent and pulse-ultrasonication for efficient extraction of crocins from gardenia fruits (gardenia jasminoides ellis) and its bioactivities. Food Chem 2022; 380: 132216
    CrossrefPubMedSearch in Google Scholar
  • 100 Thuy NM, Nhu PH, Tai NV, Minh VQ. Extraction optimization of crocin from gardenia (gardenia jasminoides ellis) fruits using response surface methodology and quality evaluation of foam-mat dried powder. Horticulturae 2022; 8: 1199
    CrossrefPubMedSearch in Google Scholar
  • 101 Sommano SR, Suppakittpaisarn P, Sringarm K, Junmahasathien T, Ruksiriwanich W. Recovery of crocins from floral tissue of gardenia jasminoides ellis. Front Nutr 2020; 7: 106
    CrossrefPubMedSearch in Google Scholar
  • 102 Rigi H, Mohtashami L, Asnaashari M, Emami SA, Tayarani-Najaran Z. Dermoprotective effects of saffron: A mini review. Curr Pharm Des 2021; 27: 4693-4698
    CrossrefPubMedSearch in Google Scholar
  • 103 Cerdá-Bernad D, Valero-Cases E, Pastor JJ, Frutos MJ. Saffron bioactives crocin, crocetin and safranal: Effect on oxidative stress and mechanisms of action. Crit Rev Food Sci Nutr 2022; 62: 3232-3249
    CrossrefPubMedSearch in Google Scholar
  • 104 Sepahi S, Golfakhrabadi M, Bonakdaran S, Lotfi H, Mohajeri SA. Effect of crocin on diabetic patients: A placebo-controlled, triple-blinded clinical trial. Clin Nutr ESPEN 2022; 50: 255-263
    CrossrefPubMedSearch in Google Scholar
  • 105 Javandoost A, Afshari A, Nikbakht-Jam I, Khademi M, Eslami S, Nosrati M, Foroutan-Tanha M, Sahebkar A, Tavalaie S, Ghayour-Mobarhan M, Ferns G, Hadizadeh F, Tabassi A, Mohajeri A. Effect of crocin, a carotenoid from saffron, on plasma cholesteryl ester transfer protein and lipid profile in subjects with metabolic syndrome: A double blind randomized clinical trial. ARYA Atheroscler 2017; 13: 245-252
    PubMedSearch in Google Scholar
  • 106 Kermani T, Kazemi T, Molki S, Ilkhani K, Sharifzadeh G, Rajabi O. The efficacy of crocin of saffron (crocus sativus L.) on the components of metabolic syndrome: A randomized controlled clinical trial. J Res Pharm Pract 2017; 6: 228
    CrossrefPubMedSearch in Google Scholar
  • 107 Sepahi S, Mohajeri SA, Hosseini SM, Khodaverdi E, Shoeibi N, Namdari M, Tabassi SAS. Effects of crocin on diabetic maculopathy: A placebo-controlled randomized clinical trial. Am J Ophthalmol 2018; 190: 89-98
    CrossrefPubMedSearch in Google Scholar
  • 108 Talaei A, Hassanpour Moghadam M, Sajadi Tabassi SA, Mohajeri SA. Crocin, the main active saffron constituent, as an adjunctive treatment in major depressive disorder: A randomized, double-blind, placebo-controlled, pilot clinical trial. J Affect Disord 2015; 174: 51-56
    CrossrefPubMedSearch in Google Scholar
  • 109 Mohebbi M, Atabaki M, Tavakkol-Afshari J, Shariati-Sarabi Z, Poursamimi J, Mohajeri SA, Mohammadi M. Significant effect of crocin on the gene expression of MicroRNA-21 and MicroRNA-155 in patients with osteoarthritis. Iran J Allergy Asthma Immunol 2022; 21: 322-331
    PubMedSearch in Google Scholar
  • 110 Abedimanesh S, Bathaie SZ, Ostadrahimi A, Asghari Jafarabadi M, Taban Sadeghi M. The effect of crocetin supplementation on markers of atherogenic risk in patients with coronary artery disease: A pilot, randomized, double-blind, placebo-controlled clinical trial. Food Funct 2019; 10: 7461-7475
    CrossrefPubMedSearch in Google Scholar
  • 111 Kuratsune H, Umigai N, Takeno R, Kajimoto Y, Nakano T. Effect of crocetin from gardenia jasminoides ellis on sleep: A pilot study. Phytomedicine 2010; 17: 840-843
    CrossrefPubMedSearch in Google Scholar
  • 112 Mori K, Torii H, Fujimoto S, Jiang X, Ikeda S, Yotsukura E, Koh S, Kurihara T, Nishida K, Tsubota K. The effect of dietary supplementation of crocetin for myopia control in children: A randomized clinical trial. J Clin Med 2019; 8: 1179
    CrossrefPubMedSearch in Google Scholar
  • 113 Furue M. Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4–JAK–STAT6/STAT3 axis: Pathogenic and therapeutic implications in atopic dermatitis. J Clin Med 2020; 9: 3741
    CrossrefPubMedSearch in Google Scholar
  • 114 Chovatiya R, Paller AS. JAK inhibitors in the treatment of atopic dermatitis. J Allergy Clin Immunol 2021; 148: 927-940
    CrossrefPubMedSearch in Google Scholar
  • 115 Simpson EL, Lacour JP, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, King BA, Thyssen JP, Silverberg JI, Bieber T, Kabashima K, Tsunemi Y, Costanzo A, Guttman-Yassky E, Beck LA, Janes JM, DeLozier AM, Gamalo M, Brinker DR, Cardillo T, Nunes FP, Paller AS, Wollenberg A, Reich K. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: Results from two randomized monotherapy phase III trials. Br J Dermatol 2020; 183: 242-255
    CrossrefPubMedSearch in Google Scholar
  • 116 Simpson E, Bissonnette R, Eichenfield LF, Guttman-Yassky E, King B, Silverberg JI, Beck LA, Bieber T, Reich K, Kabashima K, Seyger M, Siegfried E, Stingl G, Feldman SR, Menter A, Van de Kerkhof P, Yosipovitch G, Paul C, Martel P, Dubost-Brama A, Armstrong J, Chavda R, Frey S, Joubert Y, Milutinovic M, Parneix A, Teixeira HD, Lin CY, Sun L, Klekotka P, Nickoloff B, Dutronc Y, Mallbris L, Janes JM, DeLozier AM, Nunes FP, Paller AS. The validated investigator global assessment for atopic dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis. J Am Acad Dermatol 2020; 83: 839-846
    CrossrefPubMedSearch in Google Scholar
  • 117 Jin W, Huang W, Chen L, Jin M, Wang Q, Gao Z, Jin Z. Topical application of JAK1/JAK2 inhibitor momelotinib exhibits significant anti-inflammatory responses in DNCB-induced atopic dermatitis model mice. Int J Mol Sci 2018; 19: 3973
    CrossrefPubMedSearch in Google Scholar
  • 118 Kim B, Park B. [Corrigendum] Saffron carotenoids inhibit STAT3 activation and promote apoptotic progression in IL-6-stimulated liver cancer cells. Oncol Rep 2024; 51: 68
    CrossrefPubMedSearch in Google Scholar
  • 119 Tong L, Qi G. Crocin prevents platelet-derived growth factor BB-induced vascular smooth muscle cells proliferation and phenotypic switch. Mol Med Rep 2018; 17: 7595-7602
    PubMedSearch in Google Scholar
  • 120 Lei X, Zhou Z, Wang S, Jin LH. The protective effect of safranal against intestinal tissue damage in drosophila. Toxicol Appl Pharmacol 2022; 439: 115939
    CrossrefPubMedSearch in Google Scholar
  • 121 Wang L, Xian YF, Loo SKF, Ip SP, Yang W, Chan WY, Lin ZX, Wu JCY. Baicalin ameliorates 2, 4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice through modulating skin barrier function, gut microbiota and JAK/STAT pathway. Bioorg Chem 2022; 119: 105538
    CrossrefPubMedSearch in Google Scholar
  • 122 Narla S, Silverberg JI, Simpson EL. Management of inadequate response and adverse effects to dupilumab in atopic dermatitis. J Am Acad Dermatol 2022; 86: 628-636
    CrossrefPubMedSearch in Google Scholar
  • 123 Xiong Y, Wang J, Yu H, Zhang X, Miao C. Anti-asthma potential of crocin and its effect on MAPK signaling pathway in a murine model of allergic airway disease. Immunopharmacol Immunotoxicol 2015; 37: 236-243
    CrossrefPubMedSearch in Google Scholar
  • 124 Yosri H, Elkashef WF, Said E, Gameil NM. Crocin modulates IL-4/IL-13 signaling and ameliorates experimentally induced allergic airway asthma in a murine model. Int Immunopharmacol 2017; 50: 305-312
    CrossrefPubMedSearch in Google Scholar
  • 125 Otsuka A, Nomura T, Rerknimitr P, Seidel JA, Honda T, Kabashima K. The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis. Immunol Rev 2017; 278: 246-262
    CrossrefPubMedSearch in Google Scholar
  • 126 Brunner PM, Israel A, Zhang N, Leonard A, Wen HC, Huynh T, Tran G, Lyon S, Rodriguez G, Immaneni S, Wagner A, Zheng X, Estrada YD, Xu H, Krueger JG, Paller AS, Guttman-Yassky E. Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations. J Allergy Clin Immunol 2018; 141: 2094-2106
    CrossrefPubMedSearch in Google Scholar
  • 127 Bier K, Senajova Z, Henrion F, Wang Y, Bruno S, Rauld C, Hörmann LC, Barske C, Delucis-Bronn C, Bergling S, Altorfer M, Hägele J, Knehr J, Junt T, Roediger B, Röhn TA, Kolbinger F. IL-26 potentiates type 2 skin inflammation in the presence of IL-1β. J Invest Dermatol 2024; 144: 1544-1556.e9
    CrossrefPubMedSearch in Google Scholar
  • 128 Liu T, Li S, Ying S, Tang S, Ding Y, Li Y, Qiao J, Fang H. The IL-23/IL-17 pathway in inflammatory skin diseases: From bench to bedside. Front Immunol 2020; 11: 594735
    CrossrefPubMedSearch in Google Scholar
  • 129 Fernández-Albarral JA, Martínez-López MA, Marco EM, De Hoz R, Martín-Sánchez B, San Felipe D, Salobrar-García E, López-Cuenca I, Pinazo-Durán MD, Salazar JJ, Ramírez JM, López-Gallardo M, Ramírez AI. Is saffron able to prevent the dysregulation of retinal cytokines induced by ocular hypertension in mice?. J Clin Med 2021; 10: 4801
    CrossrefPubMedSearch in Google Scholar
  • 130 Poursamimi J, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohajeri SA, Ghoryani M, Mohammadi M. Immunoregulatory effects of Krocina™, a herbal medicine made of crocin, on osteoarthritis patients: A successful clinical trial in Iran. Iran J Allergy Asthma Immunol 2020; 19: 253-263
    PubMedSearch in Google Scholar
  • 131 Orfali RL, Da Silva Oliveira LM, De Lima JF, De Carvalho GC, Ramos YAL, Pereira NZ, Pereira NV, Zaniboni MC, Sotto MN, Da Silva Duarte AJ, Sato MN, Aoki V. Staphylococcus aureus enterotoxins modulate IL-22-secreting cells in adults with atopic dermatitis. Sci Rep 2018; 8: 6665
    CrossrefPubMedSearch in Google Scholar
  • 132 Meng J, Moriyama M, Feld M, Buddenkotte J, Buhl T, Szöllösi A, Zhang J, Miller P, Ghetti A, Fischer M, Reeh PW, Shan C, Wang J, Steinhoff M. New mechanism underlying IL-31-induced atopic dermatitis. J Allergy Clin Immunol 2018; 141: 1677-1689.e8
    CrossrefPubMedSearch in Google Scholar
  • 133 She M, Li T, Shi W, Li B, Zhou X. AREG is involved in scleral remodeling in form-deprivation myopia via the ERK1/2-MMP-2 pathway. FASEB J 2022; 36: e22289
    PubMedSearch in Google Scholar
  • 134 Li Q, Liu L, Jiang S, Xu Z, Lin S, Tong Y, Wang P. Optimization of the saffron compound essence formula and its effect on preventing skin photoaging. J Cosmet Dermatol 2022; 21: 1251-1262
    CrossrefPubMedSearch in Google Scholar
  • 135 Zhang X, Fan Z, Jin T. Crocin protects against cerebral- ischemia-induced damage in aged rats through maintaining the integrity of blood-brain barrier. Restor Neurol Neurosci 2017; 35: 65-75
    PubMedSearch in Google Scholar
  • 136 Macian F. NFAT proteins: Key regulators of T-cell development and function. Nat Rev Immunol 2005; 5: 472-484
    CrossrefPubMedSearch in Google Scholar
  • 137 Cury Martins J, Martins C, Aoki V, Gois AFT, Ishii HA, Da Silva EMK. Topical tacrolimus for atopic dermatitis. Cochrane Database Syst Rev 2015; (2015) CD009864
    PubMedSearch in Google Scholar
  • 138 Gisondi P, Ellis CN, Girolomoni G. Pimecrolimus in dermatology: Atopic dermatitis and beyond. Int J Clin Pract 2005; 59: 969-974
    CrossrefPubMedSearch in Google Scholar
  • 139 Agarwal S, Mirzoeva S, Readhead B, Dudley JT, Budunova I. PI3K inhibitors protect against glucocorticoid-induced skin atrophy. EBioMedicine 2019; 41: 526-537
    CrossrefPubMedSearch in Google Scholar
  • 140 Güven A. Different potent glucocorticoids, different routes of exposure but the same result: Iatrogenic Cushingʼs syndrome and adrenal insufficiency. J Clin Res Pediatr Endocrinol 2020; 12: 383-392
    CrossrefPubMedSearch in Google Scholar
  • 141 Lin CY, Shibu MA, Wen R, Day CH, Chen RJ, Kuo CH, Ho TJ, Viswanadha VP, Kuo WW, Huang CY. Leu27 IGF-II-induced hypertrophy in H9c2 cardiomyoblasts is ameliorated by saffron by regulation of calcineurin/NFAT and CaMKIIδ signaling. Environ Toxicol 2021; 36: 2475-2483
    CrossrefPubMedSearch in Google Scholar
  • 142 Boskabady MH, Seyedhosseini Tamijani SM, Rafatpanah H, Rezaei A, Alavinejad A. The effect of crocus sativus extract on human lymphocytesʼ cytokines and T helper 2/T helper 1 balance. J Med Food 2011; 14: 1538-1545
    CrossrefPubMedSearch in Google Scholar
  • 143 Shin JW, Kwon MA, Hwang J, Lee SJ, Lee JH, Kim HJ, Lee KB, Lee SJ, Jeong EM, Chung JH, Kim IG. Keratinocyte transglutaminase 2 promotes CCR6+ γδT-cell recruitment by upregulating CCL20 in psoriatic inflammation. Cell Death Dis 2020; 11: 301
    CrossrefPubMedSearch in Google Scholar
  • 144 Agnihotri N, Mehta K. Transglutaminase-2: Evolution from pedestrian protein to a promising therapeutic target. Amino Acids 2017; 49: 425-439
    CrossrefPubMedSearch in Google Scholar
  • 145 Lee SJ, Lee KB, Son YH, Shin J, Lee JH, Kim HJ, Hong AY, Bae HW, Kwon MA, Lee WJ, Kim JH, Lee DH, Jeong EM, Kim IG. Transglutaminase 2 mediates UV-induced skin inflammation by enhancing inflammatory cytokine production. Cell Death Dis 2017; 8: e3148
    CrossrefPubMedSearch in Google Scholar
  • 146 Mehta K, Kumar A, Kim HI. Transglutaminase 2: A multi-tasking protein in the complex circuitry of inflammation and cancer. Biochem Pharmacol 2010; 80: 1921-1929
    CrossrefPubMedSearch in Google Scholar
  • 147 Jeong EM, Kim CW, Cho SY, Jang GY, Shin DM, Jeon JH, Kim IG. Degradation of transglutaminase 2 by calcium-mediated ubiquitination responding to high oxidative stress. FEBS Lett 2009; 583: 648-654
    CrossrefPubMedSearch in Google Scholar
  • 148 Wang C, Cai X, Hu W, Li Z, Kong F, Chen X, Wang D. Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with alzheimerʼs disease. Int J Mol Med 2019; 43: 956-966
    PubMedSearch in Google Scholar
  • 149 Liu T, Chu X, Wang H, Zhang X, Zhang Y, Guo H, Liu Z, Dong Y, Liu H, Liu Y, Chu L, Zhang J. Crocin, a carotenoid component of crocus cativus, exerts inhibitory effects on L-type Ca(2+) current, Ca(2+) transient, and contractility in rat ventricular myocytes. Can J Physiol Pharmacol 2016; 94: 302-308
    CrossrefPubMedSearch in Google Scholar
  • 150 Zhao Z, Zheng B, Li J, Wei Z, Chu S, Han X, Chu L, Wang H, Chu X. Influence of crocetin, a natural carotenoid dicarboxylic acid in saffron, on L-type Ca2+ current, intracellular Ca2+ handling and contraction of isolated rat cardiomyocytes. Biol Pharm Bull 2020; 43: 1367-1374
    CrossrefPubMedSearch in Google Scholar
  • 151 Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: A complex and evolving relationship. Trends Microbiol 2018; 26: 484-497
    CrossrefPubMedSearch in Google Scholar
  • 152 Anderson MJ, Schaaf E, Breshears LM, Wallis HW, Johnson JR, Tkaczyk C, Sellman BR, Sun J, Peterson ML. Alpha-toxin contributes to biofilm formation among staphylococcus aureus wound isolates. Toxins (Basel) 2018; 10: 157
    CrossrefPubMedSearch in Google Scholar
  • 153 Williams MR, Nakatsuji T, Sanford JA, Vrbanac AF, Gallo RL. Staphylococcus aureus induces increased serine protease activity in keratinocytes. J Invest Dermatol 2017; 137: 377-384
    CrossrefPubMedSearch in Google Scholar
  • 154 Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, Kong HH, Amagai M, Nagao K. Dysbiosis and staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity 2015; 42: 756-766
    CrossrefPubMedSearch in Google Scholar
  • 155 Ta LDH, Chan JCY, Yap GC, Purbojati RW, Drautz-Moses DI, Koh YM, Tay CJX, Huang CH, Kioh DYQ, Woon JY, Tham EH, Loo EXL, Shek LPC, Karnani N, Goh A, Van Bever HPS, Teoh OH, Chan YH, Lay C, Knol J, Yap F, Tan KH, Chong YS, Godfrey KM, Kjelleberg S, Schuster SC, Chan ECY, Lee BW. A compromised developmental trajectory of the infant gut microbiome and metabolome in atopic eczema. Gut Microbes 2020; 12: 1-22
    CrossrefPubMedSearch in Google Scholar
  • 156 Xiao Q, Shu R, Wu C, Tong Y, Xiong Z, Zhou J, Yu C, Xie X, Fu Z. Crocin-I alleviates the depression-like behaviors probably via modulating “microbiota-gut-brain” axis in mice exposed to chronic restraint stress. J Affect Disord 2020; 276: 476-486
    CrossrefPubMedSearch in Google Scholar
  • 157 Porras G, Chassagne F, Lyles JT, Marquez L, Dettweiler M, Salam AM, Samarakoon T, Shabih S, Farrokhi DR, Quave CL. Ethnobotany and the role of plant natural products in antibiotic drug discovery. Chem Rev 2021; 121: 3495-3560
    CrossrefPubMedSearch in Google Scholar
  • 158 Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and safety of baricitinib combined with topical corticosteroids for treatment of moderate to severe atopic dermatitis: A randomized clinical trial. JAMA Dermatol 2020; 156: 1333-1343
    CrossrefPubMedSearch in Google Scholar
  • 159 Bieber T, Reich K, Paul C, Tsunemi Y, Augustin M, Lacour JP, Ghislain PD, Dutronc Y, Liao R, Yang FE, Brinker D, DeLozier AM, Meskimen E, Janes JM, Eyerich K. BREEZE-AD4 study group. Efficacy and safety of baricitinib in combination with topical corticosteroids in patients with moderate-to-severe atopic dermatitis with inadequate response, intolerance or contraindication to ciclosporin: Results from a randomized, placebo-controlled, phase III clinical trial (BREEZE-AD4). Br J Dermatol 2022; 187: 338-352
    CrossrefPubMedSearch in Google Scholar
  • 160 Feo F, Martinez J, Martinez A, Galindo PA, Cruz A, Garcia R, Guerra F, Palacios R. Occupational allergy in saffron workers. Allergy 1997; 52: 633-641
    CrossrefPubMedSearch in Google Scholar
  • 161 Varasteh AR, Vahedi F, Sankian M, Kaghazian H, Tavallaie S, Abolhassani A, Kermani T, Mahmoudi M. Specific IgG antibodies (total and subclasses) against Saffron pollen: A study of their correlation with specific IgE and immediate skin reactions. Iran J Allergy Asthma Immunol 2007; 6: 189-195
    PubMedSearch in Google Scholar
  • 162 Lu C, Ke L, Li J, Zhao H, Lu T, Mentis AFA, Wang Y, Wang Z, Polissiou MG, Tang L, Tang H, Yang K. Saffron (crocus sativus L.) and health outcomes: A meta-research review of meta-analyses and an evidence mapping study. Phytomedicine 2021; 91: 153699
    CrossrefPubMedSearch in Google Scholar
  • 163 Modaghegh MH, Shahabian M, Esmaeili HA, Rajbai O, Hosseinzadeh H. Safety evaluation of saffron (crocus sativus) tablets in healthy volunteers. Phytomedicine 2008; 15: 1032-1037
    CrossrefPubMedSearch in Google Scholar
  • 164 Mohamadpour AH, Ayati Z, Parizadeh M, Rajbai O, Hosseinzadeh H. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 2013; 16: 39-46
    PubMedSearch in Google Scholar
  • 165 Bostan HB, Mehri S, Hosseinzadeh H. Toxicology effects of saffron and its constituents: A review. Iran J Basic Med Sci 2017; 20: 110-121
    PubMedSearch in Google Scholar
  • 166 Carmona M, Zalacain A, Sánchez AM, Novella JL, Alonso GL. Crocetin esters, picrocrocin and its related compounds present in crocus sativus stigmas and gardenia jasminoides fruits. Tentative identification of seven new compounds by LC-ESI-MS. J Agric Food Chem 2006; 54: 973-979
    CrossrefPubMedSearch in Google Scholar
  • 167 Sommano SR, Suppakittpaisarn P, Sringarm K, Junmahasathien T, Ruksiriwanich W. Recovery of crocins from floral tissue of gardenia jasminoides ellis. Front Nutr 2020; 7: 106
    CrossrefPubMedSearch in Google Scholar
  • 168 Kyriakoudi A, Tsimidou MZ, OʼCallaghan YC, Galvin K, OʼBrien NM. Changes in total and individual crocetin esters upon in vitro gastrointestinal digestion of saffron aqueous extracts. J Agric Food Chem 2013; 61: 5318-5327
    CrossrefPubMedSearch in Google Scholar
  • 169 Zhang Y, Fei F, Zhen L, Zhu X, Wang J, Li S, Geng J, Sun R, Yu X, Chen T, Feng S, Wang P, Yang N, Zhu Y, Huang J, Zhao Y, Aa J, Wang G. Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats. J Chromatogr B Analyt Technol Biomed Life Sci 2017; 1044 – 1045: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 170 Sung YY, Kim HK. Crocin ameliorates atopic dermatitis symptoms by down regulation of Th2 response via blocking of NF-κB/STAT6 signaling pathways in mice. Nutrients 2018; 10: 1625
    CrossrefPubMedSearch in Google Scholar
  • 171 Alyoussef A. Crocin ameliorated atopic dermatitis induced in mice by inhibiting E-Cadherin/AKT pathway. Int J Clin Dermatol Res 2020; 8: 248-252
    PubMedSearch in Google Scholar
  • 172 Petersen EBM, Skov L, Thyssen JP, Jensen P. Role of the gut microbiota in atopic dermatitis: A systematic review. Acta Derm Venereol 2019; 99: 5-11
    PubMedSearch in Google Scholar
  • 173 Xia W, Liu B, Tang S, Yasir M, Khan I. The science behind TCM and gut microbiota interaction-their combinatorial approach holds promising therapeutic applications. Front Cell Infect Microbiol 2022; 12: 875513
    CrossrefPubMedSearch in Google Scholar
  • 174 Shih HL, Wang PH, Shih IH, Hu S, Lin JR, Hsu PY, Yang SH. Efficacy and anti-inflammatory properties of low-molecular-weight fucoidan in patients with atopic dermatitis: A randomized double-blinded placebo-controlled trial. Int J Food Prop 2024; 27: 88-105
    CrossrefPubMedSearch in Google Scholar
  • 175 Wang W, Hui PCL, Kan CW. Functionalized textile based therapy for the treatment of atopic dermatitis. Coatings 2017; 7: 82
    CrossrefPubMedSearch in Google Scholar