The antithrombosis effect of dehydroandrographolide succinate: in vitro and in vivo studies

• Published in: Pharmaceutical biology Vol. 60; no. 1; pp. 175 - 184
• Main Authors: Yin, Bowen, Zhang, Shuhua, Huang, Yuxi, Long, Yuanzhu, Chen, Yiguo, Zhao, Shiyun, Zhou, Aiqun, Cao, Minghua, Yin, Xiaoming, Luo, Daya
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: andrographolide; Animals; Antithrombin; Aspirin; Aspirin - adverse effects; Aspirin - pharmacology; Blood coagulation; Blood Coagulation - drug effects; Blood platelets; Diterpenes - administration & dosage; Diterpenes - pharmacology; Dose-Response Relationship, Drug; Female; Fibrinolytic Agents - administration & dosage; Fibrinolytic Agents - pharmacology; Gastric mucosa; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; haemorrhage; Hemorrhage; Humans; Infectious diseases; Male; Middle Aged; Platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Succinates; thromboxane; thromboxane; aspirin; Platelet aggregation; haemorrhage; andrographolide
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2021.2021948

Dehydroandrographolide succinate (DAS) is mainly used in the clinical treatment of various infectious diseases. Its potential effects on platelet aggregation and blood coagulation systems have not been reported systematically. To explore whether DAS exerts an antithrombotic effect and its internal mechanism. Human blood samples and Sprague-Dawley (SD) rats divided into control, aspirin (30 mg/kg), and DAS groups (200, 400 and 600 mg/kg) were used to measure the platelet aggregation rate, coagulation function, coagulation factor activity, and contents of thromboxane B 2 (TXB 2 ) and 6-keto-prostaglandin F 1α (6-keto-PGF 1α ). The histopathology of the SD rat gastric mucosa was also observed. All rats were administered intragastric or intraperitoneal injections once a day for 3 consecutive days. Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED 50 = 386.9 mg/kg) by decreasing TXB 2 levels (1531.95 ± 649.90 pg/mL to 511.08 ± 411.82 pg/mL) and activating antithrombin III (AT-III) (103.22 ± 16.22% to 146.46 ± 8.96%) (p < 0.05). In addition, DAS significantly enhanced the coagulation factors FV (304.12 ± 79.65% to 443.44 ± 75.04%), FVII (324.19 ± 48.03% to 790.66 ± 225.56%), FVIII (524.79 ± 115.47% to 679.92 ± 143.34%), FX (34.90 ± 7.40% to 102.76 ± 29.41%) and FXI (38.12 ± 10.33% to 65.47 ± 34.08%), increased the content of Fg (2.18 ± 0.39 to 3.61 ± 0.37 g/L), shorten the PT (10.42 ± 0.44 to 9.22 ± 0.21 s), APTT (16.43 ± 1.4 to 14.07 ± 0.75 s) and TT time (37.04 ± 2.13 to 32.68 ± 1.29 s) (p < 0.05), while the aspirin group showed no such effect on these items but showed reduced activity of FII (89.21 ± 21.72% to 61.83 ± 8.95%) and FVIII (524.79 ± 115.47% to 306.60 ± 29.96%) (p < 0.05). Histopathological changes showed aspirin-induced gastric mucosa haemorrhage and the protective effect of DAS in the gastric mucosa. DAS is more suitable than aspirin in thromboprophylaxis treatment, which provides a reliable theoretical and experimental basis for its clinical application.