biostudies-literatureYang MGBA Institute of Collaborate InnovationShenzhen Science and Technology Innovation CommitteeHong Kong Innovation Technology FundThe Key-Area Research and Development Program of Guangdong ProvinceZhongshan Municipal Bureau of Science and TechnologyGuangzhou Science and Technology Committee Research GrantHong Kong Research Grants Council Hong KongHong Kong RGC Theme based Research SchemeSpecial project of Foshan University of Science and Technology in 20198500https://www.ebi.ac.uk/biostudies/studies/S-EPMC12428957biostudies-literatureUnknown26(17)Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation and neurodegeneration. This study identified gyrophoric acid, a lichen-derived phenolic metabolite, as a dual-action Aβ42 inhibitor preventing aggregation and disassembling of mature Aβ42 fibrils. Integrated in silico studies revealed that gyrophoric acid was a strong thermodynamic stabilizer of Aβ42 (MM-GBSA: -27.3 kcal/mol) via entropically driven hydrophobic interactions and disruption of aggregation-prone conformations (100 ns MD simulations). Through biochemical analysis of the fluorescent dye thioflavin T (ThT), gyrophoric acid induced rapid Aβ42 fibril disassembly within 5 h, with time-lapse confocal microscopy quantitatively confirming the near-complete dissolution of large aggregates by 24 h. ADMET International journal of molecular sciencesThe Identification of Gyrophoric Acid, a Phytochemical Derived from Lichen, as a Potent Inhibitor for Aggregation of Amyloid Beta Peptide: In Silico and Biochemical Evaluation.PMC12428957HMRF20SC072019AG0352020B1111110006GZSTI16SC02; GZSTI17SC02PD18SC01FSUST19-SRI10ITS/500/18FP; MHP/004/21; GHP/016/21SZ; ITCPD/17-9; ITC-CNERC14SC01ZDSYS201707281432317GICI022AFD20SC01GRF 16100921HMRF18SC06TUYF19SC02T13-605/18-WDong TTLeung KWLai QWSYang MHu HXu QGao JEshboev FTsim KWKfalseThe Identification of Gyrophoric Acid, a Phytochemical Derived from Lichen, as a Potent Inhibitor for Aggregation of Amyloid Beta Peptide: In Silico and Biochemical Evaluation.Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation and neurodegeneration. This study identified gyrophoric acid, a lichen-derived phenolic metabolite, as a dual-action Aβ42 inhibitor preventing aggregation and disassembling of mature Aβ42 fibrils. Integrated in silico studies revealed that gyrophoric acid was a strong thermodynamic stabilizer of Aβ42 (MM-GBSA: -27.3 kcal/mol) via entropically driven hydrophobic interactions and disruption of aggregation-prone conformations (100 ns MD simulations). Through biochemical analysis of the fluorescent dye thioflavin T (ThT), gyrophoric acid induced rapid Aβ42 fibril disassembly within 5 h, with time-lapse confocal microscopy quantitatively confirming the near-complete dissolution of large aggregates by 24 h. ADMET 2025-01-01T00:00:00Z2025 Sep2026-04-08T19:15:06.142Z2026-04-08T12:08:45.742ZS-EPMC124289574094342110.3390/ijms26178500