Study of the Effect of Leonurus Japonicus Extract on Atopic Dermatitis
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Presented by: Javier ARRIETA ESCOBAR
Leonurus Japonicus (LJ) is one of the many plants that constitute Chinese and Kampo traditional medicines and it is known for its antioxidant and anti-inflammatory properties [1]. The major components of interest of the aerial parts of the plant are flavones, diterpenes, and alkaloids, which play an important role in free radical scavenging and helping the skin to fight against harmful external factors [2]. Moreover, they have an inhibitory effect on cyclooxygenase and lipoxygenase activity, PMNs (Polymorphonuclear neutrophils) migration [3], and also a diminution effect on several cytokines [4], [5]. Atopic dermatitis (AD) is a common, chronic inflammatory skin disorder, characterized by strong itchy, inflamed skin and chronic lichenified, scaly plaques, resulting from a complex interplay between skin barrier display function, immune dysregulation, and infectious agents [6]. Thymic Stromal Lymphopoietin protein (TSLP) is a cytokine highly produced in the epidermis by keratinocytes during AD, which can activate dendritic cells and thus initiate inflammation. It has been shown that TSLP has potential roles in the initiation, development, and progression of AD and alters the skin's barriers [7]. The production of this protein is known to be induced by a cytokine cocktail composed of TNF-α, IL-4, IL-5, and IL-13 [8].
The purpose of this study was to investigate the ability of LJ extract to regulate key genes involved in AD, by directly decreasing the proportion of the cytokine TSLP, the AD initiator, in the skin epidermis. For this experiment, skin biopsies with no stretch marks, from the abdominal skin of a 59-year-old healthy Caucasian female were selected. The cytokines cocktail was added to induce AD and treatments with LJ at 3 concentrations (0.01%, 0.02%, and 0.03%) were applied. Cyclosporin (1µM), an immunosuppressant drug, was used as a positive control of inhibition of the production of TSLP. The skin biopsies were treated with the active ingredients or cyclosporin 24h before the stress and during 24h of AD stress. The effect of the active ingredients and cyclosporin was investigated by the modulation of AD key genes using quantitative PCR and by immunohistochemistry (IHC) of TSLP skin epidermis. As a result, cytotoxicity tests showed that the LJ extract does not induce proven toxicity. Then, as the cytokine cocktail used to induce AD significantly increased the amount of TSLP in the epidermis, we provide evidence that the LJ extract represses the expression of TSLP at mRNA and protein levels. Moreover, we hypothesized that this active ingredient may also act on this condition by directly controlling key components of the inflammasome, whose dysregulation plays a major role in AD physiopathology. Consequently, LJ may be a promising solution against AD.
References
[1] X. Shang, H. Pan, X. Wang, H. He, and M. Li, “Leonurus japonicus Houtt.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine,” Journal of Ethnopharmacology, vol. 152, no. 1, pp. 14–32, Feb. 2014, doi: 10.1016/J.JEP.2013.12.052.
[2] J. Yang, J. Guo, and J. Yuan, “In vitro antioxidant properties of rutin,” LWT - Food Science and Technology, vol. 41, no. 6, pp. 1060–1066, Jul. 2008, doi: 10.1016/j.lwt.2007.06.010.
[3] L. Selloum, H. Bouriche, C. Tigrine, and C. Boudoukha, “Anti-inflammatory effect of rutin on rat paw oedema, and neutrophils chemotaxis and degranulation,” Exp Toxic Pathol, vol. 54, pp. 313–318, Oct. 2003, [Online]. Available: http://www.urbanfischer.de/journals/exptoxpath
[4] N. AlDrak, M. Abudawood, S. S. Hamed, and S. Ansar, “Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepatotoxicity,” Toxin Reviews, vol. 37, no. 3, pp. 223–230, Jul. 2018, doi: 10.1080/15569543.2017.1354305.
[5] J. K. Choi and S. H. Kim, “Rutin suppresses atopic dermatitis and allergic contact dermatitis,” Experimental Biology and Medicine, vol. 238, no. 4, pp. 410–417, Apr. 2013, doi: 10.1177/1535370213477975.
[6] T. Hajar, J. R. V. Gontijo, and J. M. Hanifin, “New and developing therapies for atopic dermatitis,” Anais Brasileiros de Dermatologia, vol. 93, no. 1, pp. 104–107, Jan. 2018, doi: 10.1590/abd1806-4841.20187682.
[7] A. K. Indra, “Epidermal TSLP: A trigger factor for pathogenesis of atopic dermatitis,” Expert Review of Proteomics, vol. 10, no. 4. pp. 309–311, Aug. 2013. doi: 10.1586/14789450.2013.814881.
[8] J. Klonowska, J. Gleń, R. J. Nowicki, and M. Trzeciak, “New cytokines in the pathogenesis of atopic dermatitis—New therapeutic targets,” International Journal of Molecular Sciences, vol. 19, no. 10. MDPI AG, Oct. 09, 2018. doi: 10.3390/ijms19103086.
The purpose of this study was to investigate the ability of LJ extract to regulate key genes involved in AD, by directly decreasing the proportion of the cytokine TSLP, the AD initiator, in the skin epidermis. For this experiment, skin biopsies with no stretch marks, from the abdominal skin of a 59-year-old healthy Caucasian female were selected. The cytokines cocktail was added to induce AD and treatments with LJ at 3 concentrations (0.01%, 0.02%, and 0.03%) were applied. Cyclosporin (1µM), an immunosuppressant drug, was used as a positive control of inhibition of the production of TSLP. The skin biopsies were treated with the active ingredients or cyclosporin 24h before the stress and during 24h of AD stress. The effect of the active ingredients and cyclosporin was investigated by the modulation of AD key genes using quantitative PCR and by immunohistochemistry (IHC) of TSLP skin epidermis. As a result, cytotoxicity tests showed that the LJ extract does not induce proven toxicity. Then, as the cytokine cocktail used to induce AD significantly increased the amount of TSLP in the epidermis, we provide evidence that the LJ extract represses the expression of TSLP at mRNA and protein levels. Moreover, we hypothesized that this active ingredient may also act on this condition by directly controlling key components of the inflammasome, whose dysregulation plays a major role in AD physiopathology. Consequently, LJ may be a promising solution against AD.
References
[1] X. Shang, H. Pan, X. Wang, H. He, and M. Li, “Leonurus japonicus Houtt.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine,” Journal of Ethnopharmacology, vol. 152, no. 1, pp. 14–32, Feb. 2014, doi: 10.1016/J.JEP.2013.12.052.
[2] J. Yang, J. Guo, and J. Yuan, “In vitro antioxidant properties of rutin,” LWT - Food Science and Technology, vol. 41, no. 6, pp. 1060–1066, Jul. 2008, doi: 10.1016/j.lwt.2007.06.010.
[3] L. Selloum, H. Bouriche, C. Tigrine, and C. Boudoukha, “Anti-inflammatory effect of rutin on rat paw oedema, and neutrophils chemotaxis and degranulation,” Exp Toxic Pathol, vol. 54, pp. 313–318, Oct. 2003, [Online]. Available: http://www.urbanfischer.de/journals/exptoxpath
[4] N. AlDrak, M. Abudawood, S. S. Hamed, and S. Ansar, “Effect of rutin on proinflammatory cytokines and oxidative stress in toxin-mediated hepatotoxicity,” Toxin Reviews, vol. 37, no. 3, pp. 223–230, Jul. 2018, doi: 10.1080/15569543.2017.1354305.
[5] J. K. Choi and S. H. Kim, “Rutin suppresses atopic dermatitis and allergic contact dermatitis,” Experimental Biology and Medicine, vol. 238, no. 4, pp. 410–417, Apr. 2013, doi: 10.1177/1535370213477975.
[6] T. Hajar, J. R. V. Gontijo, and J. M. Hanifin, “New and developing therapies for atopic dermatitis,” Anais Brasileiros de Dermatologia, vol. 93, no. 1, pp. 104–107, Jan. 2018, doi: 10.1590/abd1806-4841.20187682.
[7] A. K. Indra, “Epidermal TSLP: A trigger factor for pathogenesis of atopic dermatitis,” Expert Review of Proteomics, vol. 10, no. 4. pp. 309–311, Aug. 2013. doi: 10.1586/14789450.2013.814881.
[8] J. Klonowska, J. Gleń, R. J. Nowicki, and M. Trzeciak, “New cytokines in the pathogenesis of atopic dermatitis—New therapeutic targets,” International Journal of Molecular Sciences, vol. 19, no. 10. MDPI AG, Oct. 09, 2018. doi: 10.3390/ijms19103086.