Lilong Jiang1, Qiong Wang2, Shu Shen2, Tongshu Xiao3, Youbin Li4. 1. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China; School of Pharmacy, Hainan Medical University, Haikou 571101, China. 2. School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China. 3. Department of Phytochemistry, Jiangsu Provincial Institute of Traditional Chinese Medicine, Nanjing 210028, China. 4. School of Pharmacy, Hainan Medical University, Haikou 571101, China; Department of Phytochemistry, Jiangsu Provincial Institute of Traditional Chinese Medicine, Nanjing 210028, China. Electronic address: liyoubinli@sohu.com.
Abstract
INTRODUCTION: Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. MATERIALS AND METHODS: Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. RESULTS: Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. CONCLUSIONS: Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders.
INTRODUCTION: Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. MATERIALS AND METHODS: Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. RESULTS:Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. CONCLUSIONS:Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders.
Authors: Prutha D Aloni; Amit R Nayak; Sweta R Chaurasia; Jayant Y Deopujari; Chhaya Chourasia; Hemant J Purohit; Girdhar M Taori; Hatim F Daginawala; Rajpal S Kashyap Journal: J Tradit Complement Med Date: 2015-04-03
Authors: Reham S Ibrahim; Rahma S R Mahrous; Rasha M Abu El-Khair; Samir A Ross; Abdallah A Omar; Hoda M Fathy Journal: RSC Adv Date: 2021-03-09 Impact factor: 3.361