Journal of Traditional Chinese Medicine >
Zhenxin Anshen formula (镇心安神方) ameliorates atopic der-matitis-like skin dysfunction in mice and in vitro via regulation of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 in Neural pathways
Received date: 2022-02-20
Accepted date: 2022-06-15
Online published: 2023-08-02
Supported by
National Natural Science Foundation of China: Study on the Mechanism of Zhenxin Anshen Formula Regulating GRPR/MrgprA3/TRPs Signaling Pathway for Atop-ic Dermatitis based on the Theory of All Kinds of Diseases with Pain, Itching, and Sores are Exclusively Related to the Heart(81704087);Regulation of Zhenxin Anshen Formula on Neuroimmune Function in Atopic Dermatitis from STIM1-ORAI1 Mediated Store Oper-ated Calcium Entry(82274537);Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences: Based on PAR2/TRPV1 Pathway to Regulate Nerve-Epidermal Pruritus Information Transmission to Explore the Mechanism of Longmu Decoction on “Stress-Type Atopic Dermatitis” Mice(CI2021A02315);Belt and Road Initiative Cooperation Project of Traditional Chinese Medicine of the Chinese Academy of Traditional Chinese Medicine: Evaluation of the Effect of Chinese Medicine on Allergic Diseases and Material Basis Research(GH201910)
OBJECTIVE: To investigate the efficacy of Zhenxin Anshen formula (镇心安神方, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) signalling pathway in mice and in vitro.
METHODS: AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. BALB/c mice were divided into five groups: normal control, model control, cetirizine, low-, medium-, and high-dose of ZXAS. After ZXAS in-tervention, the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines. Immun-oglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) were de-tected by Enzyme-linked immunosorbent assay (ELISA). The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor (GRPR), TRPV1, and TRPA1 by using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, ELISA, and Western blotting were conducted for analysis of primary dorsal root ganglia (DRG) neurons in vitro.
RESULTS: ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score, number of scratching and epidermal thickness, accompanied by the de-creased IgE and Th2 inflammatory cytokines. ZXAS also supressed the mRNA and protein expression of GRPR, TRPV1, and TRPA1 in the spinal cord. The medicated sera of ZXAS decreased capsaicin-induced Ca2+ influx and downregulated the expression of TRPV1, TRPA1, and phospholipase C in DRG neurons.
CONCLUSIONS: The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca2+ signals in neurons.
Yiding ZHAO , Xiaoning YAN , Shanshan JIANG , Yong LIU , Chun DONG , Huiyan CHI , Chaoyi MAO . Zhenxin Anshen formula (镇心安神方) ameliorates atopic der-matitis-like skin dysfunction in mice and in vitro via regulation of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 in Neural pathways[J]. Journal of Traditional Chinese Medicine, 2023 , 43(5) : 887 -896 . DOI: 10.19852/j.cnki.jtcm.20230802.003
| 1. | Weidinger S, Novak N. Atopic dermatitis. Lancet 2016; 387: 1109-22. |
| 2. | Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J Invest Dermatol 2017; 137: 26-30. |
| 3. | Nutten S. Atopic dermatitis: global epidemiology and risk factors. Ann Nutr Metab 2015; 66 Suppl 1: 8-16. |
| 4. | R?nnstad ATM, Halling Overgaard AS, Hamann CR, Skov L, Egeberg A, Thyssen JP. Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: a systematic review and Meta-analysis. J Am Acad Dermatol 2018; 79: 448-56. |
| 5. | Yosipovitch G, Berger T, Fassett MS. Neuroimmune interactions in chronic itch of atopic dermatitis. J Eur Acad Dermatol Venereol 2020; 34: 239-50. |
| 6. | Yang TB, Kim BS. Pruritus in allergy and immunology. J Allergy Clin Immunol 2019; 144: 353-60. |
| 7. | Mollanazar NK, Smith PK, Yosipovitch G. Mediators of chronic pruritus in atopic dermatitis: getting the itch out? Clin Rev Allergy Immunol 2016; 51: 263-92. |
| 8. | Gouin O, L'Herondelle K, Lebonvallet N, et al. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization. Protein Cell 2017; 8: 644-61. |
| 9. | Tang L, Gao J, Cao X, Chen L, Wang H, Ding H. TRPV1 mediates itch-associated scratching and skin barrier dysfunction in DNFB-induced atopic dermatitis mice. Exp Dermatol 2021; 4: 14464. |
| 10. | Cevikbas F, Wang X, Akiyama T, et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1. J Allergy Clin Immunol 2014; 133: 448-60. |
| 11. | H?jland CR, Andersen HH, Poulsen JN, Arendt-Nielsen L, Gazerani P. A human surrogate model of itch utilizing the TRPA1 agonist trans-cinnamaldehyde. Acta Derm Venereol 2015; 95: 798-803. |
| 12. | Zhao YD, Yao CH, She YY, et al. The impact of tranquilizing method on clinical symptoms of youths and adults with atopic dermatitis. Zhong Guo Pi Fu Xing Bing Xue Za Zhi 2010; 24: 1151-53. |
| 13. | Yu K, Wang Y, Wan T, et al. Tacrolimus nanoparticles based on chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose. Int J Nanomedicine 2017; 13: 129-42. |
| 14. | Xu SY. Pharmacological experimental techniques, 3rd ed. Beijing: People's Medical Publishing House, 2002: 179-81. |
| 15. | European Task Force on Atopic Dermatitis. Severity scoring of atopic dermatitis: the SCORAD index. Consensus report of the European task force on atopic dermatitis. Dermatology 1993; 186: 23-31. |
| 16. | Shimada SG, LaMotte RH. Behavioral differentiation between itch and pain in mouse. Pain 2008; 139: 681-87. |
| 17. | Nam JH, Kim WK. The role of TRP channels in allergic inflammation and its clinical relevance. Curr Med Chem 2020; 27: 1446-68. |
| 18. | Lucaciu OC, Connell GP. Itch sensation through transient receptor potential channels: a systematic review and relevance to manual therapy. J Manipulative Physiol Ther 2013; 36: 385-93. |
| 19. | Tóth BI, Szallasi A, Bíró T. Transient receptor potential channels and itch: how deep should we scratch? Handb Exp Pharmacol 2015; 226: 89-133. |
| 20. | Chen XJ, Sun YG. Central circuit mechanisms of itch. Nat Commun 2020; 11: 3052. |
| 21. | Elmariah SB, Lerner EA. The missing link between itch and inflammation in atopic dermatitis. Cell 2013; 155: 267-69. |
| 22. | Indra AK. Epidermal TSLP: a trigger factor for pathogenesis of atopic dermatitis. Expert Rev Proteomics 2013; 10: 309-11. |
| 23. | Yang TB, Kim BS. Pruritus in allergy and immunology. J Allergy Clin Immunol 2019; 144: 353-60. |
| 24. | Garcovich S, Maurelli M, Gisondi P, Peris K, Yosipovitch G, Girolomoni G. Pruritus as a distinctive feature of type 2 inflammation. Vaccines (Basel) 2021; 9: 303. |
| 25. | Mack MR, Kim BS. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol 2018; 39: 980-91. |
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