title: Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo.
abstract: Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregation in vitro. In the present study, we investigated the in vivo efficacy and safety of compound 5 using the ferric chloride (FeCl3)-induced arterial and venous thrombosis models in rats as well as its toxicity in mice. Compared with the control rats, those treated with compound 5 showed significantly less adenosine diphosphate (ADP)-induced platelet aggregation and a prolonged activated partial thromboplastin time mediated by the specific regulation of factor VIII. Furthermore, compound 5 significantly reduced the average length and weight of thrombi in both arteries and veins. These findings were similar to those of aspirin at the same dose. The safety evaluation revealed a much lower risk of bleeding and lesser gastric mucosal damage with compound 5 than with the same dose of aspirin. An oral dose of up to 575.5mg/kg showed no toxicity in mice. In conclusion, consistent with our in vitro findings, compound 5 exhibited an in vivo antithrombotic activity that was comparable to aspirin mainly by reducing platelet aggregation and regulating factor VIII, but with fewer side effects.
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zeliang
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States.
authors.forename: Guang
authors.initials: G
authors.lastname: Xin
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Clinical Laboratory of Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, China.
authors.forename: Chengjie
authors.initials: C
authors.lastname: Ji
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.affiliation: Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: qing.xia.sppc@gmail.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; College of Mathematics, Sichuan University, Chengdu, Sichuan 610064, China. Electronic address: niuhai@scu.edu.cn.
authors.forename: Hai
authors.initials: H
authors.lastname: Niu
authors.affiliation: Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: huangwen@scu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Huang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004144:Diosgenin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015394:Molecular Structure; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D013329:Structure-Activity Relationship; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
chemical_list: D010975:Platelet Aggregation Inhibitors; D004144:Diosgenin
keywords: Anticoagulation; Aspirin; Diosgenin; Thrombosis; Toxicity