{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:35:27Z","timestamp":1760060127170,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio del Poder Popular para la Ciencia y Tecnolog\u00eda of Venezuela (MinCyt)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Several natural products have been shown to display antiviral activity against the hepatitis B virus (HBV), among a number of other viruses. In a previous study, the hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest were tested on the hepatoma cell line HepG2.2.15, which constitutively produces HBV. One of the species that exerted inhibitory activity on HBV replication was Senna silvestris. The aim of this study was the bioassay-guided purification of the ethanol fraction of leaves of S. silvestris, which displayed the most significant inhibitory activity against HBV. After solvent extraction and two rounds of reverse-phase HPLC purification, NMR analysis identified salsolinol as the compound that may exert the desired antiviral activity. The purified compound exerted inhibition of both HBV DNA and core HBV DNA. Pure salsolinol obtained from a commercial source also displayed anti-HBV DNA inhibition, with an approximate MIC value of 12 \u00b5M. Although salsolinol is widely used in Chinese traditional medicine to treat congestive heart failure, it has also been associated with Parkinson\u2019s disease. More studies are warranted to analyze the effect of changes in its chemical conformation, searching for potent antiviral, perhaps dual agents against HBV and HIV, with reduced toxicity.<\/jats:p>","DOI":"10.3390\/plants14152372","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T10:48:08Z","timestamp":1754304488000},"page":"2372","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salsolinol-Containing Senna silvestris Exerts Antiviral Activity Against Hepatitis B Virus"],"prefix":"10.3390","volume":"14","author":[{"given":"Alberto","family":"Quintero","sequence":"first","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Microbiolog\u00eda y Biolog\u00eda Celular, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"},{"name":"Laboratorio de Gen\u00e9tica y Reproducci\u00f3n Animal, Centro de Biotecnolog\u00eda Agr\u00edcola, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Maillo","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Medicinal, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nelson","family":"Gomes","sequence":"additional","affiliation":[{"name":"Unidad de Qu\u00edmica Aplicada, Centro de Qu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Gastrointestinal, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-9690","authenticated-orcid":false,"given":"Hector R.","family":"Rangel","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Microbiolog\u00eda y Biolog\u00eda Celular, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabian","family":"Michelangeli","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Gastrointestinal, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6086-6883","authenticated-orcid":false,"given":"Flor H.","family":"Pujol","sequence":"additional","affiliation":[{"name":"Laboratorio de Virolog\u00eda Molecular, Centro de Microbiolog\u00eda y Biolog\u00eda Celular, Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","first-page":"473","article-title":"Natural Products as Antiviral Agents","volume":"24","year":"2007","journal-title":"Stud. Nat. Prod. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boonstra, A., and Sari, G. (2025). HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication. Biomolecules, 15.","DOI":"10.3390\/biom15010062"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"593","DOI":"10.5009\/gnl240023","article-title":"Toward a Functional Cure for Hepatitis B","volume":"18","author":"Lok","year":"2024","journal-title":"Gut Liver"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41575-022-00724-5","article-title":"The scientific basis of combination therapy for chronic hepatitis B functional cure","volume":"20","author":"Lim","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"275","DOI":"10.2174\/138955707780059844","article-title":"Antivirals of ethnomedicinal origin: Structure-activity relationship and scope","volume":"7","author":"Chattopadhyay","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1080\/14786419.2010.535164","article-title":"Inhibition of hepatitis B virus and human immunodeficiency virus (HIV-1) replication by Warscewiczia coccinea (Vahl) Kl. (Rubiaceae) ethanol extract","volume":"25","author":"Quintero","year":"2011","journal-title":"Nat. Prod. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1021\/ac60066a017","article-title":"Improved Ferric Chloride Test for Phenols","volume":"24","author":"Soloway","year":"1952","journal-title":"Anal. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yamamura, S., and Nishiyama, S. (1991). Reduction of CX to CH2 by dissolving metals and related methods. Comprehensive Organic Synthesis, Elsevier.","DOI":"10.1016\/B978-0-08-052349-1.00229-8"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1021\/ie50164a027","article-title":"The Gelatin-Tannin Reaction","volume":"15","author":"Thomas","year":"1923","journal-title":"Ind. Eng. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1021\/jf60157a017","article-title":"Factors influencing the formation of precipitates and hazes by gelatin and condensed and hydrolysable tannins","volume":"16","author":"Calderon","year":"1968","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","first-page":"82","article-title":"Ueber einige neue Reagentien auf Alkaloide","volume":"5","author":"Dragendorff","year":"1866","journal-title":"Pharm. Zschr Russl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/jsfa.2740540206","article-title":"Afrosimetric estimation of threshold saponin concentration for bitterness in quinoa (Chenopodium quinoa Willd)","volume":"54","author":"Koziol","year":"1991","journal-title":"J. Sci. Food Agric."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/157103b0","article-title":"Liebermann-burchard reaction for steroids","volume":"157","author":"Nath","year":"1946","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/S0031-9422(02)00655-6","article-title":"Tetrahydroisoquinoline alkaloids and 2-deoxyribonolactones from Aristolochia arcuata","volume":"62","author":"Francisco","year":"2003","journal-title":"Phytochemistry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1248\/cpb.59.287","article-title":"Isolation of salsolinol, a tetrahydroisoquinoline alkaloid, from the marine sponge Xestospongia cf. vansoesti as a proteasome inhibitor","volume":"59","author":"Nagasawa","year":"2011","journal-title":"Chem. Pharm. Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.sajb.2020.11.017","article-title":"The genus Senna (Fabaceae): A review on its traditional uses, botany, phytochemistry, pharmacology and toxicology","volume":"138","author":"Oladeji","year":"2021","journal-title":"S. Afr. J. Bot."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.fitote.2009.05.008","article-title":"Senna\u00a0alata","volume":"80","author":"Hennebelle","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.jep.2014.02.042","article-title":"Anti-diabetic effects of the acetone fraction of Senna singueana stem bark in a type 2 diabetes rat model","volume":"153","author":"Ibrahim","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"199","DOI":"10.35772\/ghm.2023.01065","article-title":"Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure","volume":"5","author":"McFadden","year":"2023","journal-title":"Glob. Health Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/alcalc\/agg056","article-title":"In vitro formation of salsolinol induced by high acetaldehyde concentration in rat striatum employing microdialysis","volume":"38","author":"Jamal","year":"2003","journal-title":"Alcohol. Alcohol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0006-8993(99)02272-6","article-title":"1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism","volume":"855","author":"Storch","year":"2000","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0891-5849(97)00211-6","article-title":"Melanins from tetrahydroisoquinolines: Spectroscopic characteristics, scavenging activity and redox transfer properties","volume":"24","author":"Mosca","year":"1998","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0378-8741(00)00291-9","article-title":"In vitro pharmacological activity of the tetrahydroisoquinoline salsolinol present in products from Theobroma cacao L. like cocoa and chocolate","volume":"73","author":"Melzig","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Murata, M., Midorikawa, M., and Kawanishi, S. (2016). Molecular Link Between Alcohol and Breast Cancer: The Role of Salsolinol. Molecular Aspects of Alcohol and Nutrition, Elsevier Inc.. Chapter 25.","DOI":"10.1016\/B978-0-12-800773-0.00025-2"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1016\/S0968-0896(01)00154-7","article-title":"Simple Isoquinoline and Benzylisoquinoline alkaloids as potential antimicrobial, antimalarial, cytotoxic, and anti-HIV agents","volume":"9","author":"Iwasa","year":"2001","journal-title":"Bioorg. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1007\/s12640-017-9818-6","article-title":"Salsolinol: An Unintelligible and Double-Faced Molecule-Lessons Learned from In Vivo and In Vitro Experiments","volume":"33","author":"Panula","year":"2018","journal-title":"Neurotox. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1016\/0024-3205(92)90549-5","article-title":"Presence of methyl-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, derivatives of the neurotoxin isoquinoline, in parkinsonian lumbar CSF","volume":"50","author":"Moser","year":"1992","journal-title":"Life Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"887","DOI":"10.4103\/NRR.NRR-D-23-01592","article-title":"Salsolinol as an RNA m6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy","volume":"20","author":"Wang","year":"2025","journal-title":"Neural Regen. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1021\/tx400182n","article-title":"Oxidative DNA damage and mammary cell proliferation by alcohol-derived salsolinol","volume":"26","author":"Murata","year":"2013","journal-title":"Chem. Res. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"527","DOI":"10.3892\/etm.2023.12226","article-title":"Salsolinol improves angiotensin II-induced myocardial fibrosis in vitro via inhibition of LSD1 through regulation of the STAT3\/Notch-1 signaling pathway","volume":"26","author":"Zhang","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2277","DOI":"10.1128\/jvi.70.4.2277-2285.1996","article-title":"Protease-induced infectivity of hepatitis B virus for a human hepatoblastoma cell line","volume":"70","author":"Lu","year":"1996","journal-title":"J. Virol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/15\/2372\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:20:58Z","timestamp":1760034058000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/14\/15\/2372"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":32,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["plants14152372"],"URL":"https:\/\/doi.org\/10.3390\/plants14152372","relation":{},"ISSN":["2223-7747"],"issn-type":[{"type":"electronic","value":"2223-7747"}],"subject":[],"published":{"date-parts":[[2025,8,1]]}}}