Intervention and mechanism of Xiaoyin Anshen Yin (消银安神饮) in treatment of psoriasis combined with sleep disorders

  • Ruohan DIAO ,
  • Xingwu DUAN ,
  • Lingling LI ,
  • Tiange QU ,
  • Huishang FENG ,
  • Guangshan CHEN
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  • 1 Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China
    2 Beijing University of Chinese Medicine, Beijing 100029, China
    3 Department of Dermatology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China

Received date: 2024-10-26

  Accepted date: 2025-01-14

  Online published: 2025-05-21

Supported by

National Natural Science Foundation of China: Study on the Mechanism of Cooling Blood and Tranquilizing Mind in the Treatment of Psoriasis with Sleep Disorder based on the Regulation of Oxidative Stress by Melatonin(82074436)

Abstract

OBJECTIVE: To explore the therapeutic mechanisms of Xiaoyin Anshen Yin (消银安神饮, XYAS) in treating psoriasis associated with sleep focusing on melatonin and the regulation of the nuclear factor kappa-B (NF-κB) pathway.
METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, and administered distilled water, XYAS and its two different disassembly prescriptions by gavage respectively. Four types of drug-containing serums corresponding to the four groups were then prepared. Tumor necrosis factor (TNF)-α stimulated HaCaT was used to establish a psoriasis cell model, and the serums and the retinoid related orphan receptor alpha (RORα) inverse agonist were used respectively to intervene in the model. Enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-6 and melatonin in each group; flow cytometry was used to detect the levels of reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis; Western blot was used to evaluate the levels of superoxide dismutase 2 (SOD2), cytochrome-c (Cyt-c), inhibitor of kappa-B alpha (IκBα), p65 and phosphorylated p65.
RESULTS: XYAS and its disassembly prescriptions inhibited the secretion of inflammatory factors such as IL-6, reduced the ROS content and Cyt-c expression, increased the mitochondrial membrane potential and SOD2 content, promoted the apoptosis in HaCaT cells and inhibited the activation of the NF-κB pathway. XYAS was also found increase the melatonin content. The above effects are beneficial in the treatment of psoriasis combined with sleep disorders. Meanwhile, XYAS no longer had a significant ameliorative effect after applying the RORα inverse agonist, suggesting that the therapeutic effect of XYAS is related to RORα.
CONCLUSIONS: The results of this study confirm that XYAS can be utilized for the treatment of psoriasis combined with sleep disorders via inhibiting the NF-κB pathway, anti-inflammatory, antioxidant and pro-apoptotic, which is in part related to the regulatory role of melatonin and its receptor RORα.

Cite this article

Ruohan DIAO , Xingwu DUAN , Lingling LI , Tiange QU , Huishang FENG , Guangshan CHEN . Intervention and mechanism of Xiaoyin Anshen Yin (消银安神饮) in treatment of psoriasis combined with sleep disorders[J]. Journal of Traditional Chinese Medicine, 2025 , 45(3) : 552 -560 . DOI: 10.19852/j.cnki.jtcm.2025.03.004

References

1. Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Psoriasis. Lancet 2021; 397: 1301-15.
2. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol 2020; 182: 840-8.
3. Menter A, Strober BE, Kaplan DH, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol 2019; 80: 1029-72.
4. Baranwal N, Yu PK, Siegel NS. Sleep physiology, pathophysiology, and sleep hygiene. Prog Cardiovasc Dis 2023; 77: 59-69.
5. Smith MP, Ly K, Thibodeaux Q, et al. Factors influencing sleep difficulty and sleep quantity in the citizen pscientist psoriatic cohort. Dermatol Ther (Heidelb) 2019; 9: 511-23.
6. Luna PC, Chu CY, Fatani M, et al. Psychosocial burden of psoriasis: a systematic literature review of depression among patients with psoriasis. Dermatol Ther (Heidelb) 2023; 13: 3043-55.
7. Spencer RK, Jin JQ, Elhage KG, et al. Association between poor sleep and myocardial infarction in patients with psoriasis: findings from a cross-sectional study with the national psoriasis foundation. Dermatol Ther (Heidelb) 2023; 13: 2903-9.
8. Halioua B, Chelli C, Misery L, Taieb J, Taieb C. Sleep disorders and psoriasis: an update. Ucta Derm Venereol 2022; 102: adv00699.
9. Nowowiejska J, Baran A, Flisiak I. Mutual relationship between sleep disorders, quality of life and psychosocial aspects in patients with psoriasis. Front Psychiatry 2021; 12: 674460.
10. Gao YX, Duan XW, Wu ZM, et al. Xiaoyin Anshen Beverage (消银安神饮) in the treatment of 34 psoriasis vulgaris patients of blood-heat syndrome complicated with sleep disorder: a randomized controlled trial. Zhong Yi Za Zhi 2023; 64: 909-15.
11. Zhu Z, Yin Q, Duan X. Xiaoyin-anshen formula alleviates psoriasis complicated by sleep disturbances by regulating melatonin, antioxidant enzymes, and pro-inflammatory cytokines in mice. Front Pharmacol 2024; 15: 1427985.
12. Chen X, Zhang R, Duan X, et al. Effectiveness of Xiaoyin Jiedu granules in the treatment of psoriasis vulgaris in patients with blood-heat symptom patterns in terms of Traditional Chinese Medicine. J Tradit Chin Med 2020; 40: 863-9.
13. Lin L, Huang Z, Jianchi M, et al. Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells. Clin Exp Pharmacol Physiol 2023; 50: 903-13.
14. Zhang S, Zhang J, Yu J, et al. Hyperforin ameliorates imiquimod-induced psoriasis-like murine skin inflammation by modulating IL-17A-producing γδ T cells. Front Immunol 2021; 12: 635076.
15. Tang ZL, Zhang K, Lyu SC, Xu GW, Zhang JF, Jia HY. LncRNA MEG3 suppresses PI3K/AKT/mTOR signalling pathway to enhance autophagy and inhibit inflammation in TNF-α-treated keratinocytes and psoriatic mice. Cytokine 2021; 148: 155657.
16. Pleńkowska J, Gabig-Cimińska M, Mozolewski P. Oxidative stress as an important contributor to the pathogenesis of psoriasis. Int J Mol Sci 2020; 21: 6206.
17. Agrawal S, Singh V, Singh C, Singh A. A review on pathophysiological aspects of sleep deprivation. CNS Neurol Disord Drug Targets 2023; 22: 1194-208.
18. Krawczyk A, Mi?kiewicz J, Strzelec K, Wcis?o-Dziadecka D, Strzalka-Mrozik B. Apoptosis in autoimmunological diseases, with particular consideration of molecular aspects of psoriasis. Med Sci Monit 2020; 26: e922035.
19. Goldminz AM, Au SC, Kim N, Gottlieb AB, Lizzul PF. NF-κB: an essential transcription factor in psoriasis. J Dermatol Sci 2013; 69: 89-94.
20. Kim IW, Jeong HS, Yun HY, et al. Efficacy of horse oil on lipopolysaccharide-induced inflammation in human keratinocyte. J Tradit Chin Med 2021; 41: 355-9.
21. Chitimus DM, Popescu MR, Voiculescu SE, et al. Melatonin's impact on antioxidative and anti-inflammatory reprogramming in homeostasis and disease. Biomolecules 2020; 10: 1211.
22. Calvo JR, González-Yanes C, Maldonado MD. The role of melatonin in the cells of the innate immunity: a review. J Pineal Res 2013; 55: 103-20.
23. Kumar N, Kojetin DJ, Solt LA, et al. Identification of SR3335 (ML-176): a synthetic RORα selective inverse agonist. ACS Chem Biol 2011; 6: 218-22.
24. Rendon A, Sch?kel K. Psoriasis pathogenesis and treatment. Int J Mol Sci 2019; 20: 1475.
25. Medovic MV, Jakovljevic VL, Zivkovic VI, et al. Psoriasis between autoimmunity and oxidative stress: changes induced by different therapeutic approaches. Oxid Med Cell Longev 2022; 2022: 2249834.
26. Hu J, Bian Q, Ma X, Xu Y, Gao J. A double-edged sword: ROS related therapies in the treatment of psoriasis. Asian J Pharm Sci 2022; 17: 798-816.
27. Wroński A, Wójcik P. Impact of ROS-dependent lipid metabolism on psoriasis pathophysiology. Int J Mol Sci 2022; 23: 12137.
28. Hartmann C, Kempf A. Mitochondrial control of sleep. Curr Opin Neurobiol 2023; 81: 102733.
29. Vaccaro A, Kaplan Dor Y, Nambara K, et al. Sleep loss can cause death through accumulation of reactive oxygen species in the Gut. Cell 2020; 181: 1307-28.e15.
30. Rohleder N, Aringer M, Boentert M. Role of interleukin-6 in stress, sleep, and fatigue. Ann N Y Acad Sci 2012; 1261: 88-96.
31. Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and Meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016; 80: 40-52.
32. Xue R, Wan Y, Sun X, Zhang X, Gao W, Wu W. Nicotinic mitigation of neuroinflammation and oxidative stress after chronic sleep deprivation. Front Immunol 2019; 10: 2546.
33. Queiro R, Coto P, González-Lara L, Coto E. Genetic variants of the NF-κB pathway: unraveling the genetic architecture of psoriatic disease. Int J Mol Sci 2021; 22: 13004.
34. Gao T, Wang Z, Dong Y, et al. Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice. J Pineal Res 2019; 67: e12574.
35. Mozzanica N, Tadini G, Radaelli A, et al. Plasma melatonin levels in psoriasis. Acta Derm Venereol 1988; 68: 312-6.
36. Kartha LB, Chandrashekar L, Rajappa M, Menon V, Thappa DM, Ananthanarayanan PH. Serum melatonin levels in psoriasis and associated depressive symptoms. Clin Chem Lab Med 2014; 52: e123-5.
37. Mohammadi F, Harofteh FZ, Sahebnasagh A, Ghaneei N, Ardakani MEZ, Saghafi F. Efficacy and safety of topical rosuvastatin & melatonin vs placebo in patients with mild to moderate plaque psoriasis: a preliminary randomized double-blinded clinical trial. Skin Res Technol 2024; 30: e13689.
38. Shen Z, Jiang J, Zhou X, et al. Melatonin attenuates imiquimod-induced psoriasis-like inflammation and restores the Th17/Treg Immune Balance. Inflammation 2024; 47: 2027-40.
39. Scuderi SA, Cucinotta L, Filippone A, et al. Effect of melatonin on psoriatic phenotype in human reconstructed skin model. Biomedicines 2022; 10: 752.
40. Emet M, Ozcan H, Ozel L, Yayla M, Halici Z, Hacimuftuoglu A. A review of melatonin, its receptors and dugs. Eurasian J Med 2016; 48: 135-41.
41. Cook DN, Kang HS, Jetten AM. Retinoic acid-related orphan receptors (RORs): regulatory functions in immunity, development, circadian rhythm, and metabolism. Nucl Receptor Res 2015; 2: 101185.
42. Hall JA, Pokrovskii M, Kroehling L, et al. Transcription factor RORα enforces stability of the Th17 cell effector program by binding to a Rorc cis-regulatory element. Immunity 2022; 55: 2027-43.e9.
43. Journiac N, Jolly S, Jarvis C, et al. The nuclear receptor ROR (alpha) exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes. Proc Natl Acad Sci U S A 2009; 106: 21365-70.
44. Boukhtouche F, Vodjdani G, Jarvis CI, et al. Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis. J Neurochem 2006; 96: 1778-89.
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