Alleviative Effect of Sinapoyl Choline versus Tacrolimus on DNCB-Induced Atopic Dermatitis Murine Model
Keywords:
Atopic dermatitis, Sinapoyl choline, 2,4-Dinitrochlorobenzene, Filaggrin, MiceAbstract
Background: Atopic dermatitis (AD) is a long-lasting inflammatory skin disease characterized by erythematous, dry patches. Sinapoyl choline is a naturally occurring phenolic compound with antiinflammatory and antioxidant properties.
Aim: This study aimed to evaluate the ameliorative effect of topical sinapoylcholine in a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model of AD-like dermatitis.
Methods: Fifty male BALB/c albino mice were randomly assigned to five groups of 10 each. Except for the healthy control group, atopic dermatitis was induced by sensitization with 1% DNCB, followed by repeated challenges with 0.5% DNCB. Mice were treated topically once daily for 3 weeks with vehicle cream, 0.1% tacrolimus ointment, and 1% sinapoyl choline cream.
Results: Topical sinapoyl choline improved histopathological changes and significantly decreased clinical dermatitis scores compared to the induced group. Immunohistochemical analysis revealed that the treated mice showed increased filaggrin expression. Additionally, sinapoyl choline significantly reduced serum IgE and skin tissue IL-4, IL-13, and malondialdehyde (MDA) levels and restored reduced glutathione (GSH) levels, as demonstrated by enzyme-linked immunosorbent assay. Conclusion: Sinapoyl choline mitigates DNCB-induced AD-like symptoms by modulating inflammatory and oxidative stress responses and enhancing the epidermal barrier.
References
1. Abbas A, Abd A, Salman H, Abbas Z (2023) The Attenuated Effects of Cimifugin on Imiquimod-Induced Model of Psoriasis in Mice. Lat Am J Pharm 42: 362-369.
2. Abbas AH, Abbood MS, Ridha-Salman H, Fakhri SA, Abbas ZH, Al-Athari AJH (2025a) Suppressive effect of topical moxifloxacin on imiquimod-induced model of psoriasis in mice. Naunyn Schmiedebergs Arch Pharmacol 398: 17089-17108. doi:10.1007/s00210-025-04317-2.
3. Abbas AH, M. Hassan Z, A. Albarki M, A. Zigam Q, Ridha-Salman H, A. M. Abbas H, Ahmed AbdulAemah M, J. Abbas W, K. Raheem A, Hemid Al-Athari AJ, H. Abbas Z, K. Hajwal S, Hamzah Al-Taee M (2025b) Mitigative effects of a topically-applied combination of cimifugin and vinpocetine on a murine psoriasis-like model. Pharmakeftiki 37: doi:10.60988/p.v37i2S.134.
4. Abdulbari AS, Ali NM, Abu-Raghif AR, Matloob NA, Ridha-Salman H (2025) Impact of azithromycin on specific biochemical markers and sebum composition in acne vulgaris patients. Arch Dermatol Res 317: 798. doi:10.1007/s00403-025-04299-4.
5. Agrawal R, Woodfolk JA (2014) Skin barrier defects in atopic dermatitis topical collection on allergic skin diseases. Curr Allergy Asthma Rep 14: doi:10.1007/s11882-014-0433-9.
6. Ahn K, Kim BE, Kim J, Leung DYM (2020) Recent advances in atopic dermatitis. Curr Opin Immunol 14-21 pp. doi:10.1016/j.coi.2020.02.007.
7. Al-Rajhi SH, Hamood HM, Shihab EM, Shareef SM, Ridha-Salman H, Shahooth SS, Attarbashee RK, Abbas AH, Adham LS, Al-Bairmani RJH, Mohammed ZS, Hajwal SK (2025) Protective effect of a combined glutathione and prednisolone administration on mice subjected to a lipopolysaccharide-induced cytokine storm. Pharmakeftiki 37: 122-126. doi:10.60988/p.v37i2S.157.
8. AlBairmani RJH, Shihab EM, Ridha-Salman H, Kadhim HM, Mohammed RM, Shahooth SS, Abdalah ME, Hameed ZE, Hajwal SK, Albasri OW, Adham LS, Al-Zwaini YK (2025) D-limonene attenuates D-galactose-induced skin aging mouse model. J Mol Histol 56: 364. doi:10.1007/s10735-025-10654-6.
9. Ali BF, Abu-Raghif AR, Ridha-Salman H (2025a) Protective effect of cinnarizine on imiquimod-induced mouse model of psoriasis. J Res Pharm 29: 1783-1791. doi:10.12991/jrespharm.1734970.
10. Ali BF, Abu-Raghif AR, Ridha-Salman H, Al-Athari AJH (2025b) Vildagliptin topical ointment: an effective treatment for imiquimod-induced psoriasis in mice. J Mol Histol 56: 143. doi:10.1007/s10735-025-10416-4.
11. Ali KA, Abu-Raghif AR, Ridha-Salman H (2025c) Evaluation of common topical therapeutic agents of plane warts. Arch Dermatol Res 317: 246. doi:10.1007/s00403-024-03789-1.
12. Ashcroft DM, Dimmock P, Garside R, Stein K, Williams HC (2005) Efficacy and tolerability of topical pimecrolimus and tacrolimus in the treatment of atopic dermatitis: meta-analysis of randomised controlled trials. BMJ 330: 516.
13. Baroni A, Buommino E, De Gregorio V, Ruocco E, Ruocco V, Wolf R (2012) Structure and function of the epidermis related to barrier properties. Clin Dermatol 257-262 pp. doi:10.1016/j.clindermatol.2011.08.007.
14. Batista D, Perez L, Orfali R, Zaniboni M, Samorano L, Pereira N, Sotto M, Ishizaki A, Oliveira L, Sato M (2015) Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1/Th2/Th17 cytokines in adults with atopic dermatitis. J Eur Acad Dermatol Venereol 29: 1091-1095.
15. Bernstein ZJ, Shenoy A, Chen A, Heller NM, Spangler JB (2023) Engineering the IL‐4/IL‐13 axis for targeted immune modulation. Immunol Rev 320: 29-57.
16. Bertino L, Guarneri F, Cannavò SP, Casciaro M, Pioggia G, Gangemi S (2020) Oxidative stress and atopic dermatitis. Antioxidants (Basel) 9: 196.
17. Brunner PM, Guttman-Yassky E, Leung DYM (2017) The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol 139: S65-S76. doi:10.1016/j.jaci.2017.01.011.
18. Čelakovská J, Čermáková E, Boudková P, Krejsek J (2025) Evaluation of the levels of interleukins IL4, IL-13, IL-5, IL-10 and IL-33 in atopic dermatitis patients with and without dupilumab therapy. Front Immunol 16: 1604883.
19. Cho JH, Kwon JE, Cho Y, Kim I, Kang SC (2015) Anti-Inflammatory Effect of Angelica gigas via Heme Oxygenase (HO)-1 Expression. Nutrients 7: 4862-4874. doi:10.3390/nu7064862.
20. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL (2023) Malondialdehyde as a potential oxidative stress marker for allergy-oriented diseases: an update. Molecules 28: 5979.
21. Courtney A, Lopez DJ, Lowe AJ, Holmes Z, Su JC (2023) Burden of Disease and Unmet Needs in the Diagnosis and Management of Atopic Dermatitis in Diverse Skin Types in Australia. J Clin Med 12: doi:10.3390/jcm12113812.
22. D'Avino P, Kim J, Li M, Gessner P, Westermann P, Pat Y, Beha C, Traidl-Hoffmann C, Bost J, Gaudenzio N, Messner CB, Akdis CA, Mitamura Y (2026) Distinct Roles of IL-4, IL-13, and IL-22 in Human Skin Barrier Dysfunction and Atopic Dermatitis. Allergy 81: doi:10.1111/all.70060.
23. Dębińska A (2021a) New treatments for atopic dermatitis targeting skin barrier repair via the regulation of FLG expression. J Clin Med 10: 2506.
24. Dębińska A (2021b) New treatments for atopic dermatitis targeting skin barrier repair via the regulation of flg expression. J Clin Med pp. doi:10.3390/jcm10112506.
25. Drais HK, Albarki MA, Ridha-Salman H, Hussein AA, Drais AA (2025) Green Pharmaceutical Systems: Alpha-Tocopherol Encapsulation in Nanostructured Lipid Carriers via Microwaves-Based Technique as Advanced Topical Drug Delivery Systems. Al-Mustaqbal J Pharm Med Sci 3: 2.
26. du Sert NP, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Hurst V, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Würbel H (2020) Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0. PLoS Biol 18: e3000411-e3000411. doi:10.1371/journal.pbio.3000411.
27. Elaf Mahmood S, Muayad Sraibet A, Raad Saad L, Rana Jawad Hasan A, Hayder R-S, Samer Salim S, Rana Khairi A, Saja Majeed S, Saba Naseer A (2026) Ramelteon Ameliorates DNCB-Induced Atopic Dermatitis by Targeting Inflammatory and Oxidative Mechanisms in Mice. Curr Drug Ther 21: 1-12. doi:10.2174/0115748855433320260213203035.
28. Furue M (2020) 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 21: 5382. doi:10.3390/ijms21155382.
29. Gether L, Linares HPI, Kezic S, Jakasa I, Forman J, Sørensen OE, Storgaard H, Skov L, Røpke MA, Knop FK, Thyssen JP (2025) Skin and systemic inflammation in adults with atopic dermatitis before and after whole-body topical betamethasone 17-valerate 0.1% or tacrolimus 0.1% treatment: A randomized controlled study. J Eur Acad Dermatol Venereol 39: 308-321. doi:10.1111/jdv.20258.
30. Ghazy DN, Abu-Raghif AR, Tuama AO, Al-Asady FM, Al-Saray DA, Abed DA, Abbas SN, Ridha-Salman H (2026) Therapeutic Effect of Niclosamide versus Triamcinolone on Rabbit Ear Model of Hypertrophic Scar. Aesthetic Plast Surg doi:10.1007/s00266-026-06104-7.
31. Gong C, Pan L, Jiang Y, Sun Y, Han Y, Wang D, Wang Y (2023) Investigating the mechanism of action of Yanghe Pingchuan Granule in the treatment of bronchial asthma based on bioinformatics and experimental validation. Heliyon 9: e13000.
32. Habbas AH, Abu-Raghif AR, Ridha-Salman H, Hussein MN (2025) Therapeutic effect of bosentan on 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. Arch Dermatol Res 317: 436. doi:10.1007/s00403-025-03955-z.
33. Hameed MF, Kadhim EJ, Abu-Raghif AR (2020) Effect of topical artemisinin from artemisia annua in comparison with tacrolimus on induced atopic dermatitis in mice. J Glob Pharma Technol 12: 447-453.
34. Hasan HK, AbdElrahman MM, Aldallal AA, Salman HR, Majeed MM, Hassan MJ, Mtasher AS, Ibrahim AM (2024) Assessing Pharmacy Students' Knowledge and Awareness Regarding the Rational Utilization of Antibiotics and the Issue of Antimicrobial Resistance in Iraq. Al-Mustaqbal J Pharm Med Sci 2: 2.
35. Hassan ZY, Hassan TY, Abu-Raghif AR (2022) Evaluation the Effectiveness of Phenolic Compound of Salvia frigida on Induced Atopic Dermatitis in Experimental Mice. Iraqi J Pharm Sci 31: 154-166. doi:10.31351/vol31iss1pp154-166.
36. Hassan ZY, Hassan TY, Abu Raghif AR (2023) Evaluation the Effect of Phytosterol Fraction of Chenopodium Murale in Comparison with Tacrolimus on Mice Induced Atopic Dermatitis. Iraqi J Pharm Sci 32: 84-91. doi:10.31351/vol32iss1pp84-91.
37. He H, Gao X, Wang X, Li X, Jiang X, Xie Z, Ma K, Ma J, Umezawa K, Zhang Y (2019) Comparison of anti-atopic dermatitis activities between DHMEQ and tacrolimus ointments in mouse model without stratum corneum. Int Immunopharmacol 71: 43-51. doi:10.1016/j.intimp.2019.03.015.
38. He S, Liang X, Chen W, Nima Y, Li Y, Gu Z, Lai S, Zhong F, Qiu C, Mo Y, Tang J, Wu G (2025) Osthole ameliorates chronic pruritus in 2,4-dichloronitrobenzene-induced atopic dermatitis by inhibiting IL-31 production. Chin Herb Med 17: 368-379. doi:10.1016/j.chmed.2024.01.003.
39. Hussein MN, Abu-Raghif AR, Ridha-Salman H, Shareef SM, Attarbashee RK, Hajwal SK, Habbas AH (2025) Flavonoids from Conyza Canadensis mitigates CDNB-induced mouse model of atopic dermatitis. Comp Clin Pathol 34: 987-1010. doi:10.1007/s00580-025-03709-3.
40. Idan HM, Hasani RAM, Othman IQ (2024) Effect of anemia on oral cavity and hematological assessments. Diyala J Med 26: 153-162. doi:10.26505/djm.v26i1.1087.
41. Ilves T, Tiitu V, Suttle M-M, Saarinen JV, Harvima IT (2015) Epidermal expression of filaggrin/profilaggrin is decreased in atopic dermatitis: reverse association with mast cell tryptase and IL-6 but not with clinical severity. Dermatitis 26: 260-267.
42. Ingurgio A (2024) Long-term topical corticosteroid treatment for atopic dermatitis: an in-depth analysis of safety, efficacy, withdrawal, and patient experiences. Drugs Ther Perspect 40: 269-275.
43. Jaafar FR, Attarbashee RK, Abu-Raghif AR, Ridha-Salman H (2025) Gemifloxacin ameliorates acetic acid-induced ulcerative colitis via modulation of inflammatory, oxidative, and adhesive biomarkers and histopathological changes in rats. J Mol Histol 56: 250. doi:10.1007/s10735-025-10527-y.
44. Ji H, Li XK (2016) Oxidative Stress in Atopic Dermatitis. Oxid Med Cell Longev 2016: 2721469. doi:10.1155/2016/2721469.
45. Jin Z, Yin L, Huang Z (2025) Sinapic Acid Attenuates Hypertrophic Scarring by Modulating the TGFβ1/Smad Pathway: An In Vivo and In Vitro Investigation. Int J Clin Pract 2025: 3671828. doi:10.1155/ijcp/3671828.
46. Kaltalioglu K (2023) Sinapic acid-loaded gel accelerates diabetic wound healing process by promoting re-epithelialization and attenuating oxidative stress in rats. Biomed Pharmacother 163: 114788.
47. Kang R, Kim EJ, Park S, Lee H, Kim E-Y, Sohn Y, Jung H-S (2025) Effects of Sinapine on inflammatory responses in keratinocytes and atopic dermatitis-like lesions. Korea J Herbology 40: 45-57.
48. Kasim VNKM, Lee YZ, Bakrin IH, Hussain MK, Israf DA, Shaari K, Tan JW, Lee MT, Tham CL (2024) Oral and topical administration of a geranyl acetophenone attenuates DNCB-induced atopic dermatitis-like skin lesions in BALB/c mice. Sci Rep 14: 17623.
49. Khafaji AWM, Al-Zubaidy AAK, Farhood IG, Salman HR (2024) Ameliorative effects of topical ramelteon on imiquimod-induced psoriasiform inflammation in mice. Naunyn Schmiedebergs Arch Pharmacol 397: 6231-6248. doi:10.1007/s00210-024-03017-7.
50. Khorsheed SM, Abu Raghif AR (2024) Anti-proliferative, Anti-oxidant and Anti-inflammatory Effects of Topical Rutin on Imiquimod-Induced Psoriasis in Mice. Pak J Life Soc Sci 22: 1962-1976. doi:10.57239/PJLSS-2024-22.1.00142.
51. Kim H, Kim JR, Kang H, Choi J, Yang H, Lee P, Kim J, Lee KW (2014) 7,8,4′-Trihydroxyisoflavone Attenuates DNCB-Induced Atopic Dermatitis-Like Symptoms in NC/Nga Mice. PLoS One 9: e104938. doi:10.1371/journal.pone.0104938.
52. Kim HM, Kang YM, Jin BR, Lee H, Lee DS, Lee M, An HJ (2023) Morus alba fruits attenuates atopic dermatitis symptoms and pathology in vivo and in vitro via the regulation of barrier function, immune response and pruritus. Phytomedicine 109: 154579. doi:10.1016/j.phymed.2022.154579.
53. Kim MJ, Ryu H, Jeong HH, Van JY, Hwang JY, Kim AR, Seo J, Moon KM, Jung WK, Lee B (2024) The beneficial effects of ethanolic extract of Sargassum serratifolium in DNCB-induced mouse model of atopic dermatitis. Sci Rep 14: 62828. doi:10.1038/s41598-024-62828-z.
54. Kraaijeveld R, Li Y, Yan L, de Leur K, Dieterich M, Peeters AMA, Wang L, Shi Y, Baan CC (2019) Inhibition of T Helper Cell Differentiation by Tacrolimus or Sirolimus Results in Reduced B-Cell Activation: Effects on T Follicular Helper Cells. Transplant Proc 51: 3463-3473. doi:10.1016/j.transproceed.2019.08.039.
55. Kurebayashi AK, Phan K, Abdoh A, Andreo-Filho N, Lopes PS, Mohammed Y, Leite-Silva VR (2024) Strategic approaches in formulation development for atopic dermatitis. Cosmetics 11: 113.
56. Kvedariene V, Vaskovic M, Semyte JB (2025a) Role of oxidative stress and antioxidants in the course of atopic dermatitis. Int J Mol Sci 26: 4210.
57. Kvedariene V, Vaskovic M, Semyte JB (2025b) Role of Oxidative Stress and Antioxidants in the Course of Atopic dermatitis. Int J Mol Sci pp. doi:10.3390/ijms26094210.
58. Langan SM, Irvine AD, Weidinger S (2020) Atopic dermatitis. Lancet 396: 345-360. doi:10.1016/S0140-6736(20)31286-1.
59. Leary SL (2020) AVMA guidelines for the euthanasia of animals: 2020 edition. Am Vet Med Assoc 121-121 pp.
60. Lee JH, Im DS (2022) Honokiol suppresses 2,6-dinitrochlorobenzene-induced atopic dermatitis in mice. J Ethnopharmacol 289: 115023. doi:10.1016/j.jep.2022.115023.
61. Leung DYM, Guttman-Yassky E (2017) Assessing the current treatment of atopic dermatitis: Unmet needs. J Allergy Clin Immunol S47-S48 pp. doi:10.1016/j.jaci.2017.01.010.
62. Li Y, Duan M, Liu G, Liang L, Liu X, Zhang J, Wen C, Xu X (2024) Effect of Sinapine on Microstructure and Anti-Digestion Properties of Dual-Protein-Based Hydrogels. Foods 13: 3237. doi:10.3390/foods13203237.
63. Li Y, Li J, Su Q, Liu Y (2019) Sinapine reduces non-alcoholic fatty liver disease in mice by modulating the composition of the gut microbiota. Food Funct 10: 3637-3649. doi:10.1039/c9fo00195f.
64. Li Y, Xu Y-J, Tan CP, Liu Y (2022) Sinapine Improves LPS-Induced Oxidative Stress in Hepatocytes by Down-Regulating MCJ Protein Expression. SSRN Electron J doi:10.2139/ssrn.4118388.
65. Liu A, Liao B, Yin S, Ye Z, He M, Li X, Liu Y, Xu Y (2023) Quantitative Proteomic Analysis Reveals the Mechanisms of Sinapine Alleviate Macrophage Foaming. Molecules 28: 2012. doi:10.3390/molecules28052012.
66. Liu Y, Wang C, Li M, Zhu Y, Liu K, Liu Y, Luo M, Zhang C (2024) Natural ingredients in the regulation of abnormal lipid peroxidation: a potential therapy for pulmonary diseases. Front Pharmacol 15: 1507194.
67. Luo Y, Hu J, Zhou Z, Zhang Y, Wu Y, Sun J (2025) Oxidative stress products and managements in atopic dermatitis. Front Med (Lausanne) 12: 1538194.
68. Mahdi ZA, Abu-Raghif AR, Shahooth SS, Ali KA, Al abood RM, Al Khafaji AS, Ridha-Salman H (2026) Amlodipine topical cream: an effective hair growth promoter for an alopecia mouse model via VEGF-mediated angiogenesis and vasodilation. Arch Dermatol Res 318: 134. doi:10.1007/s00403-026-04597-5.
69. Malviya N, Prabakaran A, Alexander A (2023) Comparative study on ethosomes and transferosomes for enhancing skin permeability of sinapic acid. J Mol Liq 383: 122098.
70. Martinović N, Poklar Ulrih N, Abramovič H (2019) Sinapic Acid and its Derivatives Increase Oxidative Stability in Different Model Lipid Systems. Eur J Lipid Sci Technol 121: 1800326. doi:10.1002/ejlt.201800326.
71. Mekkey SM, Ameen MA, Hadi NK (2024) A Study of Serum Levels of Ferritin, Hepatic and Renal functions in Beta-Thalassemia Major (BTM) Patients Treated With Deferasirox (DFX) Tablets, Desferioxamine (DFO) Vial, or Combination of Both (DFX+ DFO) in Thalassemia Center/Karbala. Al-Mustaqbal J Pharm Med Sci 2: 4.
72. Menezes JCJMDS, Campos VR (2024) Unlocking the Potential of Hydroxycinnamic Acid Bioconjugates: Tailored Derivatives for Biomedical, Cosmetic, and Food Applications. Compounds 604-625 pp. doi:10.3390/compounds4040037.
73. Mitroi GG, Pleșea EL, Mitroi GF, Mitroi MR, Neagoe CD, Ianoși SL (2024) Exploring the potential of IL-4 and IL-13 plasma levels as biomarkers in atopic dermatitis. Life (Basel) 14: 352.
74. Mo Ku J, Hyang Hong S, Re Kim S, Choi H-S, In Kim H, Uk Kim D, Mi Oh S, Sook Seo H, Young Kim T, Cheol Shin Y, Cheon C, Ko S-G (2018) The prevention of 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in BALB/c mice by Jawoongo. BMC Complement Altern Med 18: 197. doi:10.1186/s12906-018-2280-z.
75. Mohiuddin AK (2019) Skin care creams: formulation and use. Dermatol Clin Res 5: 238-271.
76. Nagano N, Araki A, Ishikawa N, Nagase M, Adachi K, Ishimura N, Ishihara S, Kinoshita Y, Maruyama R (2021) Immunohistochemical expression of filaggrin is decreased in proton pump inhibitor non-responders compared with proton pump inhibitor responders of eosinophilic esophagitis. Esophagus 18: 362-371. doi:10.1007/s10388-020-00781-2.
77. Najim RA, Sharquie KE, Abu-Raghif AR (2007) Oxidative stress in patients with Behcet's disease: I correlation with severity and clinical parameters. J Dermatol 34: 308-314. doi:10.1111/j.1346-8138.2007.00278.x.
78. Natella F, Nardini M, Di Felice M, Scaccini C (1999) Benzoic and cinnamic acid derivatives as antioxidants: structure-activity relation. J Agric Food Chem 47: 1453-1459. doi:10.1021/jf980737w.
79. Nguyen VPT, Stewart JD, Ioannou I, Allais F (2021) Sinapic Acid and Sinapate Esters in Brassica: Innate Accumulation, Biosynthesis, Accessibility via Chemical Synthesis or Recovery From Biomass, and Biological Activities. Front Chem 9: 664602. doi:10.3389/fchem.2021.664602.
80. Nićiforović N, Abramovič H (2014) Sinapic Acid and Its Derivatives: Natural Sources and Bioactivity. Compr Rev Food Sci Food Saf 13: 34-51. doi:10.1111/1541-4337.12041.
81. Nie W, Zhao X, Zhang Y, Zeng C, Yang H, Liu B (2025) Chlorogenic acid alleviates DNCB-induced atopic dermatitis by inhibiting the Akt1/NF-κB signaling pathway. Eur J Pharmacol 998: 177534. doi:10.1016/j.ejphar.2025.177534.
82. Park JH, Hwang MH, Cho YR, Hong SS, Kang JS, Kim WH, Yang SH, Seo DW, Oh JS, Ahn EK (2020) Combretum quadrangulare Extract Attenuates Atopic Dermatitis-Like Skin Lesions through Modulation of MAPK Signaling in BALB/c Mice. Molecules 25: 2003. doi:10.3390/molecules25082003.
83. Pascual JC, Fleisher AB (2004) Tacrolimus ointment (Protopic) for atopic dermatitis. Skin Therapy Lett 9: 1-5.
84. Pekkarinen SS, Stöckmann H, Schwarz K, Heinonen IM, Hopia AI (1999) Antioxidant activity and partitioning of phenolic acids in bulk and emulsified methyl linoleate. J Agric Food Chem 47: 3036-3043. doi:10.1021/jf9813236.
85. Pena J, Zameza PA, Pixley JN, Remitz A, Feldman SR (2023) A comparison of topical corticosteroids and topical calcineurin inhibitors for the treatment of atopic dermatitis. J Allergy Clin Immunol Pract 11: 1347-1359.
86. Pierozan P, Jernerén F, Ransome Y, Karlsson O (2017) The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers. Basic Clin Pharmacol Toxicol 121: 113-118. doi:10.1111/bcpt.12774.
87. Proksch E, Brandner JM, Jensen JM (2008) The skin: An indispensable barrier. Exp Dermatol 17: 1063-1072. doi:10.1111/j.1600-0625.2008.00786.x.
88. Riedl R, Kühn A, Rietz D, Hebecker B, Glowalla KG, Peltner LK, Jordan PM, Werz O, Lorkowski S, Wiegand C, Wallert M (2023) Establishment and Characterization of Mild Atopic Dermatitis in the DNCB-Induced Mouse Model. Int J Mol Sci 24: 12325. doi:10.3390/ijms241512325.
89. Rossi M, Bettolini L, Artelli GL, Fraghì A, Tomasi C, Calzavara-Pinton P (2023) Dupilumab Treatment Efficacy and Impact on Clinical Scores, Serum Biomarkers, and Itch in Adult Patients with Atopic Dermatitis: A Retrospective Analysis. J Asthma Allergy 16: 1233-1240. doi:10.2147/JAA.S433515.
90. Saeedavi M, Goudarzi M, Mehrzadi S, Basir Z, Hasanvand A, Hosseinzadeh A (2022a) Sinapic acid ameliorates airway inflammation in murine ovalbumin-induced allergic asthma by reducing Th2 cytokine production. Life Sci 307: 120858. doi:10.1016/j.lfs.2022.120858.
91. Saeedavi M, Goudarzi M, Mehrzadi S, Basir Z, Hasanvand A, Hosseinzadeh A (2022b) Sinapic acid ameliorates airway inflammation in murine ovalbumin-induced allergic asthma by reducing Th2 cytokine production. Life Sci 307: 120858.
92. Shallal AM, Abu-Raghif AR, Ridha-Salman H, Al-Zheery WH, Al-Athari AJH (2025) Ezetimibe mitigates DNCB-induced mouse model of eczematous dermatitis. Eur J Clin Exp Med 23: 882-897. doi:10.15584/ejcem.2025.4.7.
93. Sharif SJ, Kadhim HM, Ahmed BS, Ridha-Salman H (2026a) Gastroprotective and therapeutic effects of emodin on rat model of diclofenac-induced gastric ulceration. Naunyn Schmiedebergs Arch Pharmacol 399: 4519-4536. doi:10.1007/s00210-025-04701-y.
94. Sharif SJ, Kadhim HM, Ridha-Salman H, Hussein AH (2026b) Gastroprotective effect of salvianolic acid B on rat model of diclofenac-induced gastric ulceration. Comp Clin Pathol 35: doi:10.1007/s00580-026-03758-2.
95. Sharquie KE, Turki KM, Abu-Raghif AR, Al-Geboori HG (2005) Oxidative stress in patients with premature hair grayness. Saudi Med J 26: 1310-1311.
96. Shihab EM, Al-Abbassi MG, Al Wahab Al Shukri DA, Taha Ahmad I (2018) Role of estrogen in the oxidation process in postmenopausal osteoporosis. J Glob Pharma Technol 10: 80-85.
97. Shihab EM, Kadhim HM, Shahooth SS (2025) The impact of carvedilol on level of interleukin-6, superoxide dismutase, elastin levels and epidermal thickness in experimentally aging induced mice model. J Res Pharm 29: 11-19. doi:10.12991/jrespharm.1626210.
98. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, Silverberg JI, Deleuran M, Kataoka Y, Lacour J-P, Kingo K, Worm M, Poulin Y, Wollenberg A, Soo Y, Graham NMH, Pirozzi G, Akinlade B, Staudinger H, Mastey V, Eckert L, Gadkari A, Stahl N, Yancopoulos GD, Ardeleanu M (2016) Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med 375: 2335-2348. doi:10.1056/nejmoa1610020.
99. Sinapine-enriched rapeseed oils reduced fatty liver formation in high-fat diet-fed C57BL/6J mice (2020) RSC Adv doi:10.1039/D0RA00215A.
100. Styrczewska M, Zuk M, Boba A, Zalewski I, Kulma A (2019) Use of natural components derived from oil seed plants for treatment of inflammatory skin diseases. Curr Pharm Des 25: 2241-2263.
101. Tahir A (2024) Ethnopharmacology, Phytochemistry, and Pharmacological Potential of Philenoptera laxiflora: An Emerging African Medicinal Plant for Drug Discovery. Al-Mustaqbal J Pharm Med Sci 4: 3.
102. Talamonti M, Galluzzo M, Silvaggio D, Lombardo P, Tartaglia C, Bianchi L (2021) Quality of life and psychological impact in patients with atopic dermatitis. J Clin Med 10: 1298. doi:10.3390/jcm10061298.
103. Umar BU, Rahman S, Dutta S, Islam T, Nusrat N, Chowdhury K, Binti Wan Ahmad Fakuradzi WFS, Haque M (2022) Management of Atopic Dermatitis: The Role of Tacrolimus. Cureus 14: e28130. doi:10.7759/cureus.28130.
104. Walters KA, Lane ME (2020) Dermal and Transdermal Drug Delivery Systems. Dermal Drug Delivery 1-60. doi:10.1201/9781315374215-1.
105. Watanabe T, Hamada K, Tategaki A, Kishida H, Tanaka H, Kitano M, Miyamoto T (2009) Oral Administration of Lactic Acid Bacteria Isolated from Traditional South Asian Fermented Milk `Dahi' Inhibits the Development of Atopic Dermatitis in NC/Nga Mice. J Nutr Sci Vitaminol (Tokyo) 55: 271-278. doi:10.3177/jnsv.55.271.
106. Wei H, Chen Z, Lai W, Wang W, Bian X, Zhang L, Li X (2025) Aqueous extracts of Portulaca oleracea L. alleviate atopic dermatitis by restoring skin barrier function. Front Pharmacol 16: 1591394. doi:10.3389/fphar.2025.1591394.
107. Weidinger S, Novak N (2016) Atopic dermatitis. Lancet 387: 1109-1122. doi:10.1016/S0140-6736(15)00149-X.
108. Wollenberg A, Reitamo S, Atzori F, Lahfa M, Ruzicka T, Healy E, Giannetti A, Bieber T, Vyas J, Deleuran M (2008) Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment. Allergy 63: 742-750.
109. Yang Z, Lu D, Hong E-K, Zhang B, Jiang M, Yang Y, Zhang D (2020) Extraction and separation of sinapine from rapeseed cake and the mode of action of melanin production inhibition. Mol Biol (Mosc) 54: 911-918.
110. Yates K, Pohl F, Busch M, Mozer A, Watters L, Shiryaev A, Kong Thoo Lin P (2019) Determination of sinapine in rapeseed pomace extract: Its antioxidant and acetylcholinesterase inhibition properties. Food Chem 276: 768-775. doi:10.1016/j.foodchem.2018.10.045.
111. Zhang Q, Xia Y, Wang F, Yang D, Liang Z (2024) Induction of ferroptosis by natural products in non-small cell lung cancer: a comprehensive systematic review. Front Pharmacol 15: 1385565.
112. Zou Y, Kim AR, Kim JE, Choi JS, Chung HY (2002) Peroxynitrite scavenging activity of sinapic acid (3,5-dimethoxy-4-hydroxycinnamic acid) isolated from Brassica juncea. J Agric Food Chem 50: 5884-5890. doi:10.1021/jf020496z.
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