The Potent of Constituents from Leunca Fruits (Solanum nigrum Linn.) as Anti-Skin Aging against TYRP-1: Molecular Docking and ADME-Tox

Faruk Jayanto Kelutur; Agriyaningsih Oktaviana Hadi

Authors

Faruk Jayanto Kelutur Study Program of Pharmacy, Institute of Health Science Salsabila Serang
Agriyaningsih Oktaviana Hadi Study Program of Midwifery, Institute of Health Science Salsabila Serang

Keywords:

ADME-Tox, leunca, molecular docking, TYRP-1

Abstract

Leunca fruits are a source of natural antioxidants with compounds that have been reported, namely quercetin, solasodine, solanine, solamargine, and solasonine. However, its effectiveness as an anti-skin aging has not been studied. In the skin, melanin is produced by melanocytes in the deepest layer of the epidermis, thus protecting the skin from damage caused by sunlight radiation. Moreover, pregnant women can also cutaneous changes due to hyperpigmentation by skin lesions. If the formation of abnormal melanin, it is necessary to inhibit the tyrosinase enzyme, TYRP-1. This research was conducted by predicting the interaction between compounds of leunca fruits and the enzyme of TYRP-1 using Audock Tooks 1.5.6. Then, from the molecular docking results, ADMET-Tox was carried out with pre-ADMET to determine transdermal drug delivery and safety when used as a product. The results of in silico molecular docking showed that solasodine and quercetin had a higher binding affinity (G, -8.58 and -7.74 kcal/mol; Ki, 517.15 and 2110 nM) compared to kojic acid (-5.50 kcal/mol; 92720 nM) as a reference. The amino acid His192 becomes a crucial residue when hydrogen interacts based on visualization. While ADME-Tox, solasodine fulfills the safety of the transdermal route. Therefore, this compound can potentially be anti-skin aging from the leunca fruits. Apart from that as a drug topical for pregnant women when melanogenesis in the epidermal melanocytes.

References

Abdullah, S.S., Putra, P.P., Antasionasti, I., Rundengan, G., Suoth, E.J., Abdullah, R.P.I., Abdullah, F., 2021. Analisis Sifat Fisikokimia, Farmakokinetik, dan Toksikologi pada Pericarpium Pala (Myristica fragrans) secara Artificial Intelligence. Chem. Prog. 14, 81. https://doi.org/10.35799/cp.14.2.2021.37112

Ahmad, Z., Damayanti, 2018. Penuaan Kulit: Patofisiologi dan Manifestasi Klinis. Berk. Ilmu Kesehat. Kulit dan Kelamin-Period. Dermatology Venereol. 30, 208–215.

Arba, M., Yamin, Ihsan, S., Tjahjono, D.H., 2018. Computational approach toward targeting the interaction of porphyrin derivatives with Bcl-2. J. Appl. Pharm. Sci. 8, 60–66. https://doi.org/10.7324/JAPS.2018.81208

Biswas, R., Chanda, J., Kar, A., Mukherjee, P.K., 2017. Tyrosinase Inhibitory Mechanism of Betulinic Acid from Dillenia indica. Food Chem. 232, 689–696. https://doi.org/10.1016/j.foodchem.2017.04.008

Chagas, C.M., Moss, S., Alisaraie, L., 2018. Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski’s Rule of Five. Int. J. Pharm. 549, 133–149. https://doi.org/10.1016/j.ijpharm.2018.07.046

Filoni, A., Mariano, M., Cameli, N., 2019. Melasma: How hormones can modulate skin pigmentation. J. Cosmet. Dermatol. 18, 458–463. https://doi.org/10.1111/jocd.12877

Halim, Y., Effendi, D., Nurwitri, C.C., 2018. Pemanfaatan Buah Leunca (Solanum nigrum L.) dalm Pembuatan Minuman Sari Buah. FaST- J. Sais dan Teknol. 2, 58–70.

Hariyanti, Kusmardi, Yanuar, A., Hayun, 2021. Ligand Based Pharmacophore Modeling , Virtual Screening, and Molecular Docking Studies of Asymmetrical Hexahydro-2H-Indazole Analogs of Curcumin (AIACs) to Discover Novel Estrogen Receptors Alpha (ER-alpha) Inhibitor. Indones. J. Chem. 21, 137–147. https://doi.org/10.22146/ijc.54745

Husnia, F., Budiarti, A., 2021. Pengembangan Metode Analisis Kuersetin dalam Ekstrak Etanol Buah Leunca (Solanum nigrum L.) menggunakan Kromatografi Cair Kinerja Tinggi. Media Farm. 17, 108–115.

Jain, A.N., Nicholls, A., 2008. Recommendations for evaluation of computational methods. J. Comput. Aided. Mol. Des. 22, 133–139. https://doi.org/10.1007/s10822-008-9196-5

Karmakar, U.K., Tarafder, U.K., Sadhu, S.K., Biswas, N.N., Shill, M.C., 2010. Biological Investigations of Dried Fruit of Solanum nigrum Linn. Stamford J. Pharm. Sci. 3, 38–45. https://doi.org/10.3329/sjps.v3i1.6796

Kartasasmita, R.E., Herowati, R., Harmastuti, N., Gusdinar, T., 2009. Quercetin Derivatives Docking Based on Study of Flavonoids Interaction to Cyclooxygenase-2. Indones. J. Chem. 9, 297–302.

Kelutur, F.J., 2023. Anti-Breast Cancer Activities from the Sea Fan (Gorgonia mariae): Pharmacophore Screening and in-silico Molecular Docking Study, in CHEMISTRY BEYOND BORDERS: INTERNATIONAL CONFERENCE ON PHYSICAL CHEMISTRY: The 1st Annual Meeting of the Physical Chemistry Division of the Indonesian Chemical Society. AIP Publishing, USA, pp. 1–11. https://doi.org/10.1063/5.0174619

Kelutur, F.J., 2022. Sterol Constituents of Sea Fan (Gorgonia mariae) as Potential Candidates of MPro Protein SARS-CoV-2 Inhibitor : in silico Study. Indones. J. Chem. Res. 9, 185–196. https://doi.org/10.30598/ijcr

Kelutur, F.J., Mustarichie, R., 2020. Molecular Docking of The Potential Compounds from Cocoa Shells (Theobroma cacao L.) Against Androgen Receptor as Anti-Alopecia. J. Glob. Pharma Technol. 12, 52–60.

Kelutur, F.J., Ode, W., Fitriah, I., 2022. Potential Components of Gedi Leaves (Abelmoschus manihot L. Medik) as XO Enzyme Inhibitors Causing Gout: an in silico Approach, in Proceeding of The 1st Mandala Waluya–International Conference on Pharmaceutical Science and Practice. pp. 1–15.

Kelutur, F.J., Saptarini, N.M., Mustarichie, R., Kurnia, D., 2021. Molecular Docking of the Terpenes in Gorgonian Corals to COX-2 and iNOS Enzymes as Anti-Inflammatory. Lett. Drug Des. Discov. 9, 1–16. https://doi.org/10.2174/1570180819666211227162950

Khaerunnisa, N., Saraswati, I., Sasikirana, W., Farmasi, P.S., Diponegoro, U., 2022. Kandungan Total Fenolik Ekstrak Metanol Buah Leunca (Solanum nigrum L .) dan Fraksi-Fraksinya. Generics J. Res. Pharm. 2, 86–92.

Kim, R., Skolnick, J., 2008. Assessment of Programs for Ligand Binding Affinity Prediction. J. Comput. Chem. 29, 1316–1330.

Maack, A., Pegard, A., 2016. Populus nigra (Salicaceae) Absolute Rich in Phenolic Acids, Phenylpropanoids and Flavonoids as a New Potent Tyrosinase Inhibitor. Fitoterapia 111, 95–101. https://doi.org/10.1016/j.fitote.2016.04.001

Meng, X.-Y., Zhang, H.-X., Mezei, M., Cui, M., 2011. Molecular Docking: A Powerful Approach for Structure-Based Drug Discovery. Curr. Comput. Aided-Drug Des. 7, 146–157. https://doi.org/10.2174/157340911795677602

Morris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Olson, A.J., 2009. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem. 30, 2785–2791. https://doi.org/10.1002/jcc.21256

Muchtaridi, Yanuar, A., Megantara, S., Purnomo, H., 2018. Kimia Medisinal: Dasar-Dasar dalam Perancangan Obat, Pertama. ed. Prenamedia Group, Jakarta

Nisa, K., Surbakti, E.S.B., 2016. Tomat (Lycopersicum esculentum Mill .) sebagai Anti Penuaan Kulit. Majority 5, 73–78.

Opo, F.A.D.M., Rahman, M.M., Ahammad, F., Ahmed, I., Bhuiyan, M.A., Asiri, A.M., 2021. Structure-based pharmacophore modeling, virtual screening, molecular docking, and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein. Sci. Rep. 11, 1–18. https://doi.org/10.1038/s41598-021-83626-x

Putra, I.B., Jusuf, N.K., Dewi, N.K., 2022. Skin Changes and Safety Profile of Topical Products During Pregnancy. J. Clin. Aesthet. Dermatol. 15, 49–57.

Umamaheswari, M., Madeswaran, A., Asokkumar, K., 2013. Virtual Screening Analysis and in-vitro Xanthine Oxidase Inhibitory Activity of Some Commercially Available Flavonoids. Iran. J. Pharm. Res. 12, 317–23.

Wibowo, S., Sri Widyarti, Sabarudin, A., Soeatmadji, D.W., Sumitro, S.B., 2019. The Role of Astaxanthin Compared with Metformin in Preventing Glycated Human Serum Albumin from Possible Unfolding: A Molecular Dynamic Study. Asian J. Pharm. Clin. Res. 12, 276–282. https://doi.org/10.22159/ajpcr.2019.v12i9.34617

Xie, C., Jin, J., Lv, X., Tao, J., Wang, R., Miao, D., 2015. Anti-aging effect of transplanted amniotic membrane mesenchymal stem cells in a premature aging model of bmi-1 deficiency. Sci. Rep. 5, 1–18. https://doi.org/10.1038/srep13975

Zolghadri, S., Bahrami, A., Hassan Khan, M.T., Munoz-Munoz, J., Garcia-Molina, F., Garcia-Canovas, F., Saboury, A.A., 2019. A Comprehensive Review on Tyrosinase Inhibitors. J. Enzyme Inhib. Med. Chem. 34, 279–309. https://doi.org/10.1080/14756366.2018.1545767