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

Pharm Biol. 2022 Dec;60(1):175-184. doi: 10.1080/13880209.2021.2021948.

Abstract

Context: 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.

Objective: To explore whether DAS exerts an antithrombotic effect and its internal mechanism.

Materials and methods: 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 B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α). 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.

Results: Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED50 = 386.9 mg/kg) by decreasing TXB2 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.

Conclusions: DAS is more suitable than aspirin in thromboprophylaxis treatment, which provides a reliable theoretical and experimental basis for its clinical application.

Keywords: Platelet aggregation; andrographolide; aspirin; haemorrhage; thromboxane.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Aspirin / adverse effects
  • Aspirin / pharmacology
  • Blood Coagulation / drug effects
  • Diterpenes / administration & dosage
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / pharmacology*
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Humans
  • Male
  • Middle Aged
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Succinates

Substances

  • Diterpenes
  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Succinates
  • Aspirin
  • dehydroandrographolide

Grants and funding

This work was supported by the Health Commission of Jiangxi Province under the Chinese Medicine Research Project of Jiangxi Province [No. 2017A305] (Xiaoming Yin) and the Natural Science Foundation of Jiangxi Province [No. 20192BAB205007] (Shuhua Zhang).