{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T08:13:55Z","timestamp":1781856835180,"version":"3.54.5"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T00:00:00Z","timestamp":1682640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Directorate of Research and Community Engagement Universitas Padjadjaran"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Alopecia is a condition in which hair on the scalp or other areas of the body is lost or falls out excessively. Nutritional deficiency causes blood flow to the head to decrease causing the hormone testosterone to be changed by the enzyme 5-\u03b1-reductase to dihydrotestosterone, which inhibits the growth phase and accelerates the death phase. One of the methods developed to treat alopecia is through inhibition of the 5-\u03b1-reductase enzyme, which converts testosterone to its more potent metabolite, dihydrotestosterone (DHT). Ethnomedicinally, Merremia peltata leaf is used by the people of Sulawesi as a remedy for baldness. Therefore, in this research, an in vivo study was conducted on rabbits to determine the anti-alopecia activity of M. peltata leaf compounds. The structure of the compounds isolated from the M. peltata leaf ethyl acetate fraction was determined by analysis of NMR and LC-MS data. An in silico study was then carried out using minoxidil as a comparison ligand; scopolin (1) and scopoletin (2) isolated from M. peltata leaf were identified as anti-alopecia compounds by predicting docking, simulating molecular dynamics and predicting absorption, distribution, metabolism, excretion, and toxicology (ADME-Tox). Compounds 1 and 2 had a better effect on hair growth compared to positive controls, and NMR and LC-MS analysis showed that they had comparable binding energies to receptors in the molecular docking interaction study: \u22124.51 and \u22124.65 kcal\/mol, respectively, compared to \u22124.8 kcal\/mol for minoxidil. Molecular dynamics simulation analysis with the parameters binding free energy calculated using the MM-PBSA method and complex stability based on SASA, PCA, RMSD, and RMSF showed that scopolin (1) has a good affinity for androgens receptors. The ADME-Tox prediction for scopolin (1) showed good results for the parameters of skin permeability, absorption and distribution. Therefore, scopolin (1) is a potential antagonist to androgen receptors and could be useful in the treatment of alopecia.<\/jats:p>","DOI":"10.3390\/ph16050669","type":"journal-article","created":{"date-parts":[[2023,4,28]],"date-time":"2023-04-28T09:54:53Z","timestamp":1682675693000},"page":"669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-Alopecia Activity of Coumarin Derivatives Isolated from Merremia peltata Leaves and Computational Study of Their Binding to Androgen Receptors Using Molecular Docking and Molecular Dynamic Simulation"],"prefix":"10.3390","volume":"16","author":[{"given":"Syawal","family":"Abdurrahman","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia"},{"name":"Department of Medical Laboratory Technology, Universitas Mandala Waluya, Kendari 93231, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslin","family":"Ruslin","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Universitas Halu Oleo, Kendari 93231, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4085-7872","authenticated-orcid":false,"given":"Aliya Nur","family":"Hasanah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mus","family":"Ifaya","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Universitas Mandala Waluya, Kendari 93231, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6453-0236","authenticated-orcid":false,"given":"Resmi","family":"Mustarichie","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"ref_1","first-page":"42","article-title":"Comparison of anti-dandruff activity of synthetic shampoos and crude plant extracts on dandruff causing isolates","volume":"4","author":"Obasi","year":"2018","journal-title":"J. Bio. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5826\/dpc.0701a01","article-title":"Diet and hair loss: Effects of nutrient deficiency and supplement use","volume":"7","author":"Guo","year":"2017","journal-title":"Dermatol. Pract. Concept."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/jocd.12930","article-title":"An overview of herbal alternatives in androgenetic alopecia","volume":"18","author":"Dhariwala","year":"2019","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_4","unstructured":"Justine, A.E., Rodney, S., and Stephen, B.H. (2002). Androgenetic Alopecia: Pathogenesis and Potential for Therapy, Cambridge University Press."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.mce.2017.09.009","article-title":"Androgens and androgen receptor action in skin and hair follicles","volume":"465","author":"Ceruti","year":"2018","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1166\/asl.2012.3657","article-title":"In vivo hair growth promotion activity of gel containing niosomes loaded with the Oryza sativa bran fraction (OSF3)","volume":"16","author":"Manosroi","year":"2012","journal-title":"Adv. Sci. Lett."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12020-017-1280-y","article-title":"Androgenetic alopecia: A review","volume":"57","author":"Lolli","year":"2017","journal-title":"Endocrine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/1523-1747.ep12335779","article-title":"Different levels of 5\u03b1-reductase type I and II, aromatase, and androgen receptor in hair follicles of women and men with androgenetic alopecia","volume":"109","author":"Sawaya","year":"1997","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"246","DOI":"10.19046\/abp.v02i06.01","article-title":"Alopecia and the herbal drugs: An overview of the current status","volume":"2","author":"Semwal","year":"2015","journal-title":"Adv. Biomed. Pharm."},{"key":"ref_10","unstructured":"Ruslin, and Sahidin, I (2008). Identification and determination of traditional medicinal plants in Southeast Sulawesi community at Arboretum Prof. Mahmud Hamundu Haluoleo University. Maj. Farm. Ind., 19, 101\u2013107."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1123047","DOI":"10.1155\/2022\/1123047","article-title":"Active Antialopecia Chemical Identification of Merremia peltata Leaves and Computational Study toward Androgen Receptor Using Molecular Docking and Molecular Dynamic Simulation","volume":"2022","author":"Abdurrahman","year":"2022","journal-title":"Sci. World J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"132","DOI":"10.4103\/japtr.JAPTR_222_20","article-title":"Molecular docking studies and ADME-Tox prediction of phytocompounds from Merremia peltata as a potential anti-alopecia treatment","volume":"12","author":"Abdurrahman","year":"2021","journal-title":"J. Adv. Pharm. Technol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9942","DOI":"10.1021\/acs.jpca.0c06430","article-title":"Cryogenic Infrared Action Spectroscopy Fingerprints the Hydrogen Bonding Network in Gas-Phase Coumarin Cations","volume":"124","author":"Carrascosa","year":"2020","journal-title":"J. Phys. Chem. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.18517\/ijaseit.5.2.504","article-title":"Isolation and Characterization of Scopoletin from The Bark of Fragraea ceilanica thumb and Antioxidants Tests","volume":"5","author":"Ferdinal","year":"2015","journal-title":"Int. J. Adv. Sci. Eng. Inf. Tech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40543-019-0193-1","article-title":"In vitro and in vivo anti-aging effects of compounds isolated from Artemisia iwayomogi","volume":"10","author":"Kim","year":"2019","journal-title":"J. Anal. Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1007\/s11418-020-01397-7","article-title":"5,6-Dihydro-\u03b1-pyrones from the leaves of Cryptocarya pulchinervia (Lauraceae)","volume":"74","author":"Juliawati","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_17","first-page":"138","article-title":"Isolation and structure elucidation of Scopoletin from Ipomoea reniformis (Convolvulaceae)","volume":"1","author":"Mehul","year":"2011","journal-title":"J. App. Pharm. Sci."},{"key":"ref_18","first-page":"319","article-title":"Male androgenetic alopecia","volume":"44","author":"Rodney","year":"2004","journal-title":"JMG"},{"key":"ref_19","first-page":"1316","article-title":"Psychological effect, pathophysiology, and management of androgenetic alopecia in men","volume":"10","author":"Dow","year":"2005","journal-title":"Mayo. Clinic. Proceeding"},{"key":"ref_20","first-page":"37","article-title":"Effect of oral finasteride on serum androgen levels and androgenetic alopecia in adult men","volume":"18","author":"Bayoumy","year":"2007","journal-title":"J. Pan-Arab. Leag. Dermatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.jaad.2008.07.001","article-title":"Medical treatments for male and female patter hair loss","volume":"59","author":"Nicole","year":"2008","journal-title":"J. Am Acad. Dermatol."},{"key":"ref_22","first-page":"32","article-title":"Advances in the management of androgen deficiency in women","volume":"1","author":"Guay","year":"2001","journal-title":"Med. Asp. Hum. Sex."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ramirez, D., and Caballero, J. (2018). Is It Reliable to Take the Molecular Docking Top Scoring Position as the Best Solution without Considering Available Structural Data. Molecules, 23.","DOI":"10.3390\/molecules23051038"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"200","DOI":"10.4172\/jpb.1000140","article-title":"Molecular docking studies of curcumin derivatives with multiple protein targets for procarcinogen activating enzyme inhibition, J","volume":"3","author":"Girija","year":"2010","journal-title":"J. Proteomics. Bio. Inform."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3742","DOI":"10.1039\/c3tb20193g","article-title":"Hydrogen bonds in molecular solids-from biological systems to organic electronics","volume":"1","author":"Glowacki","year":"2013","journal-title":"J. Mater. Chem. B"},{"key":"ref_26","first-page":"301","article-title":"Electrostatic interactions in macromolecules: Theory and applications","volume":"19","author":"Sharp","year":"1990","journal-title":"Annu. Rev. Bio. Phys. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16074","DOI":"10.1073\/pnas.0708036104","article-title":"A surface on the androgen receptor that allosterically regulates coactivator binding","volume":"104","author":"Perpina","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1096\/fasebj.9.7.7737462","article-title":"The hydrophobic effect in protein folding","volume":"9","author":"Lins","year":"1995","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1016\/j.bmcl.2016.02.088","article-title":"7-Substituted umbelliferone derivatives as androgen receptor antagonists for the potential treatment of prostate and breast cancer","volume":"26","author":"Kendel","year":"2016","journal-title":"Bio. Med. Chem. Let."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Koga, H., Negishi, M., Konoshita, M., Fujii, S., Mori, S., Ishigami, M., Kawachi, E., Kagechiki, H., and Tanatani, A. (2020). Development of androgen-antagonistic coumarinamides with a unique aromatic folded pharmacophore. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155584"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3389\/fchem.2020.00199","article-title":"Geranylated Coumarins From Thai Medicinal Plant Mammea siamensis With Testosterone 5\u03b1-Reductase Inhibitory Activity","volume":"8","author":"Morikawa","year":"2020","journal-title":"Front. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Pitalokas, D.A.E., Ramadhan, D.S.F., Chaidir, L., and Fakih, T.M. (2021). Docking-based virtual screening and molecular dynamics simulations of quercetin analogs as enoyl-acyl carrier protein reductase (Inh A) inhibitors of Mycobacterium tuberculosis. J. Sci. Pharm., 89.","DOI":"10.3390\/scipharm89020020"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mannhold, R. (2008). Molecular Drug Properties: Measurement and Prediction, Wiley-VHC Verlag.","DOI":"10.1002\/9783527621286"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1021\/ci049884m","article-title":"ADME evaluation in drug discovery correlation of Caco-2 permeation with simple molecular properties","volume":"44","author":"Hou","year":"2004","journal-title":"J. Chem. Inf. Com. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1348\/000709905X52210","article-title":"Comparing groups in a before-after design: When t-test and ANCOVA produce different results","volume":"76","author":"Wright","year":"2006","journal-title":"Br. J. Educ. Psychol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e4737","DOI":"10.7717\/peerj.4737","article-title":"Nature-derived lignan compound VB-1 exerts hair growth-promoting effects by augmenting Wnt\/\u03b2-Catenin signaling in human dermal papilla cells","volume":"6","author":"Luo","year":"2018","journal-title":"PeerJ"},{"key":"ref_38","first-page":"1849","article-title":"Anti-alopecia activity of DADAP (Erythrina variegata L.) leaves ethanol extract","volume":"9","author":"Mustarichie","year":"2017","journal-title":"J. Pharm. Sci."},{"key":"ref_39","unstructured":"BIOVIA (2021, December 10). Dassault Syst\u00e8mes. Discovery Studio Visualizer, v21.1.0.20298; Dassault Syst\u00e8mes: San Diego, CA, USA, 2021. Available online: https:\/\/discover.3ds.com\/discovery-studio-visualizer-download."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/s10822-008-9196-5","article-title":"Recommendations for evaluation of computational methods","volume":"22","author":"Jain","year":"2008","journal-title":"J. Com. Aid. Mol. Des."},{"key":"ref_41","first-page":"19","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1","author":"Abraham","year":"2015","journal-title":"Softw. X"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_43","unstructured":"Silverstein, R.M., Webster, F.X., and Kiemle, D.J. (2005). Spectrometric Identification of Organic Compounds, John Wiley & Sons. Inc.. [7th ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1093\/clinchem\/35.7.1288","article-title":"High-performance liquid chromatography\/mass spectrometry: State of the art for the drug analysis laboratory","volume":"35","author":"Bowers","year":"1989","journal-title":"Clin. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Silva, S.D., Alan, W., Wim, F. (2012). ACPYPE\u2014Antechamber Python Parser Interface. BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-367"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9954","DOI":"10.1021\/jp003020w","article-title":"Structure and dynamics of the TIP3P, SPC, and SPC\/E water models at 298 K","volume":"43","author":"Mark","year":"2001","journal-title":"J. Phys. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1055\/s-2008-1075009","article-title":"Bioassay of crude drugs for hair growth promoting activity in mice by a new simple method","volume":"40","author":"Tanaka","year":"1980","journal-title":"Plant. Med."},{"key":"ref_49","unstructured":"Federer, W. (1963). Experimental Design, Theory, and Application, MacMillan."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/669\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:25:57Z","timestamp":1760124357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/16\/5\/669"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,28]]},"references-count":49,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ph16050669"],"URL":"https:\/\/doi.org\/10.3390\/ph16050669","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,28]]}}}