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

Publisher: Taylor & Francis Country of Publication: England NLM ID: 9812552 Publication Model: Print Cited Medium: Internet ISSN: 1744-5116 (Electronic) Linking ISSN: 13880209 NLM ISO Abbreviation: Pharm Biol Subsets: MEDLINE

Publication: [London] : Taylor & Francis
Original Publication: Lisse, the Netherlands : Swets & Zeitlinger, c1998-

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

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

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

0 (Diterpenes)
0 (Fibrinolytic Agents)
0 (Platelet Aggregation Inhibitors)
0 (Succinates)
R16CO5Y76E (Aspirin)
TKB45D7LVX (dehydroandrographolide)

Date Created: 20220111 Date Completed: 20220223 Latest Revision: 20220430

20231215

PMC8757605

10.1080/13880209.2021.2021948

35014931