In Vitro And In Silico Studies Of Lawsone On Inflammation-Induced Skin Cells For Development Of Skin Anti-Inflammatory Treatment

Shazleen Sofea Abdullah; Muhammad Alif Mohammad Latif; Siti Farah Md Tohid

doi:10.55230/mabjournal.v53i3.2801

Authors

Shazleen Sofea Abdullah Laboratory of Halal Science Research, Halal Product Research Institute, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Muhammad Alif Mohammad Latif Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Siti Farah Md Tohid
sitifarah@upm.edu.my
Laboratory of Halal Science Research, Halal Product Research Institute, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia; Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

Keywords:

elisa, lawsone, molecular docking, molecular dynamic, skin inlfammation, TNF-alpha

Abstract

Lawsone, an active phytoconstituent of Lawsonia inermis sp., is proposed as a safer alternative for the current skin anti-inflammatory treatments that are mainly steroidal with unwanted side effects which does not conform to the concept of halalan toyyiban in medicine. This study aims to investigate the inhibitory mechanism of lawsone on pro-inflammatory cytokine, TNF (tumour necrosis factor)-α through in silico and in vitro methods. The inhibitory mechanism of lawsone were investigated via molecular docking and molecular dynamics which were performed via AutoDock Vina and GROMACS softwares, respectively. The results were then analysed via PyMol, Proteins Plus, RMSD and RMSF graphs. Subsequently, cytotoxicity of lawsone towards A431 skin epidermoid and 3T3 fibroblast cells, was determined via MTT assay. Lawsone was further tested on A431 cells stimulated with ethanol (200 mM) or hydrogen peroxide (250 µM) for 24 hours (acute) and 48 hours (chronic) to induce pro-inflammatory cytokine (TNF-α) release. Cell viabilities were determined via MTT assay and expression of TNF-α were measured via ELISA. In silico works predicted lawsone’s ability to bind to TNF-α with good binding affinity without disruption to the protein’s structure stability.Lawsone is proven to be safe towards non-pathological cells. Lawsone exhibited significant anti-inflammatory effect on inflammation induced A431 epidermoid cells. ELISA results were not as expected as compared to previous in silico study, but an anti-inflammatory pattern can be observed in the chronic ethanol-induced treatment groups. In conclusion, lawsone is shown to have potential to be developed as a halalan-toyyiban alternative for skin anti-inflammatory treatment.

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References

Abdallah, F., Mijouin, L. & Pichon, C. 2017. Skin immune landscape: Inside and outside the organism. Mediators of Inflammation, 2017: 1-17.

Avena-Woods, C. 2017. Overview of atopic dermatitis. American Journal of Managed Care, 23: 115-123.

Badoni Semwal, R., Semwal, D. K., Combrinck, S., Cartwright-Jones, C. & Viljoen, A. 2014. Lawsonia inermis L. (henna): Ethnobotanical, phytochemical and pharmacological aspects. Journal of Ethnopharmacology, 155(1): 80-103.

Balkrishna, A., Nain, P., Chauhan, A., Sharma, N., Gupta, A., Ranjan, R. & Varshney, A. 2020. Super critical fluid extracted fatty acids from Withania somnifera seeds repair psoriasis-like skin lesions and attenuate pro-inflammatory cytokines (TNF-α and IL-6) release. Biomolecules, 10(2): 185.

Bauer, P., Hess, B. & Lindahl, E. 2022. GROMACS 2022.1 Manual.

Coondoo, A., Phiske, M., Verma, S. & Lahiri, K. 2014. Side-effects of topical steroids: A long overdue revisit. Indian Dermatology Online Journal, 5(4): 416.

Ghosh, A. & Coondoo, A. 2017. Systemic side effects of topical corticosteroids. In: A Treatise on Topical Corticosteroids in Dermatology. K. Lahiri (Ed.). Singapore, Springer. pp. 241–249.

Jade, D.D., Pandey, R., Kumar, R. & Gupta, D. 2020. Ligand-based pharmacophore modeling of TNF-α to design novel inhibitors using virtual screening and molecular dynamics. Journal of Biomolecular Structure and Dynamics, 40(4): 1702-1718.

Kenakin, T.P. 2021. A Pharmacology Primer: Theory Applications and Methods. 3rd Ed. Elsevier.

Langkilde A., Olsen, L. C., Sætrom, P., Drabløs, F., Besenbacher, S., Raaby, L., Johansen, C. & Iversen, L. 2016. Pathway analysis of skin from psoriasis patients after adalimumab treatment reveals new early events in the anti-inflammatory mechanism of anti-TNF-α. PLoS ONE, 11(12): e0167437.

Neuman, M.G., Nanau, R. M., Oruña, L. & Coto, G. 2011. In vitro anti-inflammatory effects of hyaluronic acid in ethanol-induced damage in skin cells. Journal of Pharmacy & Pharmaceutical Sciences, 14(3): 425.

Pulsipher, K.J., Szeto, M.D., Rundle, C. W., Presley, C.L., Laughter, M.R. & Dellavalle, R.P. 2021. Global burden of skin disease representation in the literature: Bibliometric analysis. JMIR Dermatology, 4(2): e29282.

Qaiser, H., Saeed, M., Nerukh, D. & Ul-Haq, Z. 2020. Structural insight into TNF-α inhibitors through combining pharmacophore-based virtual screening and molecular dynamic simulation. Journal of Biomolecular Structure and Dynamics, 39(16): 5920-5939.

Saha, T., Rifat, T. & Shimanto, S. 2019. Prospects of halal pharmaceuticals. Asian Journal of Ethnopharmacology and Medicinal Foods, 5(2): 17-23.

Schwingen, J., Kaplan, M. & Kurschus, F.C. 2020. Review—current concepts in inflammatory skin diseases evolved by transcriptome analysis: In-depth analysis of atopic dermatitis and psoriasis. International Journal of Molecular Sciences, 21(3): 699.

Trott, O. & Olson, A.J. 2010. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31(2): 455-461.

Wolff, K., Goldsmith, L., Katz, S., Gilchrest, B., Paller, A.S. & Leffell, D. 2011. Fitzpatrick's Dermatology in General Medicine. 8th Ed. McGraw-Hill.