Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Chinensinaphthol methyl ether prevents thrombosis by inhibiting the intrinsic pathway of coagulation through targeting coagulation factor XII.
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Zhang Hui, Zhang Ting, Zhou Panyao, Liu Yating, Chen Siyi, Lei Zhouxuan, Su Jinyu, Ge Jingxin, Ye Ling, Li Ziyao, Yang Yanfang, Wu Hezhen, Liu Bo
Аннотация
BACKGROUND: Thrombotic disorders rank among the leading cause of morbidity and mortality globally. Dysregulated coagulation and platelet aggregation are key factors in thrombus formation. Identifying effective agents that target both platelet aggregation and coagulation is essential for improving treatment outcomes.
METHODS: We evaluated the antithrombotic properties of Chinensinaphthol methyl ether (CME) in vivo, a lignan from Rostellularia procumbens (L.) Nees . Using platelet proteomics, we assessed CME's impact on coagulation and platelet activation proteins. Liver transcriptomic and plasma proteomic analyses were performed to investigate CME's effects on coagulation factor expression. Molecular docking, differential scanning fluorimetry (DSF), and bio-layer interferometry (BLI) were used to identify CME's target. Additionally, molecular dynamics simulations and amino acid mutation studies were conducted to understand CME's binding mechanism.
RESULTS: CME exhibited significant antithrombotic effects, inhibiting platelet aggregation and the intrinsic coagulation pathway. Platelet proteomics showed a marked down-regulation of proteins in the complement-coagulation cascade. Analyses of liver and plasma proteomics indicated that CME does not affect the transcription or expression of coagulation factors. Molecular docking and other assays confirmed that coagulation factor ⅩⅡ (F12) is CME's primary target. Molecular dynamics and mutation studies revealed that CME binds to the FnI domain of F12, blocking its activation to F12a and thereby preventing coagulation system activation.
CONCLUSION: This study is the first to clarify the antithrombotic mechanism of the lignan compound CME targeting F12. Its "dual effects and low bleeding risk" avoids the bleeding risks associated with clinical combination therapy, provides a novel small-molecule candidate drug for thrombotic diseases, and fills the research gap in natural small molecules targeting F12.
METHODS: We evaluated the antithrombotic properties of Chinensinaphthol methyl ether (CME) in vivo, a lignan from Rostellularia procumbens (L.) Nees . Using platelet proteomics, we assessed CME's impact on coagulation and platelet activation proteins. Liver transcriptomic and plasma proteomic analyses were performed to investigate CME's effects on coagulation factor expression. Molecular docking, differential scanning fluorimetry (DSF), and bio-layer interferometry (BLI) were used to identify CME's target. Additionally, molecular dynamics simulations and amino acid mutation studies were conducted to understand CME's binding mechanism.
RESULTS: CME exhibited significant antithrombotic effects, inhibiting platelet aggregation and the intrinsic coagulation pathway. Platelet proteomics showed a marked down-regulation of proteins in the complement-coagulation cascade. Analyses of liver and plasma proteomics indicated that CME does not affect the transcription or expression of coagulation factors. Molecular docking and other assays confirmed that coagulation factor ⅩⅡ (F12) is CME's primary target. Molecular dynamics and mutation studies revealed that CME binds to the FnI domain of F12, blocking its activation to F12a and thereby preventing coagulation system activation.
CONCLUSION: This study is the first to clarify the antithrombotic mechanism of the lignan compound CME targeting F12. Its "dual effects and low bleeding risk" avoids the bleeding risks associated with clinical combination therapy, provides a novel small-molecule candidate drug for thrombotic diseases, and fills the research gap in natural small molecules targeting F12.