Shahrekord University of Medical Sciences Journal of Herbmed Pharmacology 2345-5004 15 1 2026 01 01 Cytotoxicity activity and in silico studies from ethanol, ethyl acetate, and n-hexane extracts of Marchantia paleacea liverwort herb on MCF-7 and T47D breast cancer cells 36 50 10.34172/jhp.2026.53139 EN Dicki Bakhtiar Purkon https://orcid.org/0000-0001-8188-1580 Irvan Herdiana https://orcid.org/0009-0006-7083-5283 Mimin Kusmiyati https://orcid.org/0000-0001-9918-4660 Eva Dania Kosasih https://orcid.org/0009-0005-6642-9410 Nur Aji https://orcid.org/0000-0002-4337-6441 Faizah Min Fadhlillah https://orcid.org/0000-0002-2579-5781 Muhamad Iqbal Ramadhianto https://orcid.org/0009-0000-8359-741X Jihan Amirah Salsabila Putri Dwi Handayani Journal Article 10.34172/jhp.2026.53139 2025 05 07 2025 11 26 Introduction: Marchantia paleacea contains macrocyclic bisbibenzyls, including marchantins with known cytotoxic, antioxidant, and antimicrobial activities, with no known mechanism of action. This study aimed to evaluate the cytotoxic potential of three solvent extracts—70% ethanol (EEMP), ethyl acetate (EAEMP), and n-hexane (NHEMP)—of M. paleacea and to assess molecular interactions of their bioactive compounds through in silico simulations against cancer-related proteins. Methods: Cytotoxicity was determined on MCF-7 and T47D breast cancer cell lines using the MTT assay, with doxorubicin as a positive control. Chemical profiling of the most active extract was performed using Fourier-transform infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS), followed by molecular docking against carbonic anhydrase II (CA-II, PDB ID: 1T47) and cyclin-dependent kinase 2 (CDK2, PDB ID: 1T46). Results: Among the tested extracts, EAEMP showed the strongest cytotoxicity (IC₅₀ = 8.68 µg/mL for MCF-7; 12.78 µg/mL for T47D), compared with EEMP (119.2 and 64.33 µg/mL) and NHEMP (62.07 and 229.8 µg/mL). GC–MS identified Marchantin A, B, and C as major constituents, with Marchantin C exhibiting the highest docking affinity (ΔG = −8.62 kcal/mol) at residues D810 and E640. Conclusion: The ethyl-acetate extract of M. paleacea demonstrates significant in vitro and in silico anticancer potential, suggesting its promise as a semi-polar source of cytotoxic bisbibenzyl compounds for future natural anticancer drug development.