The Antithrombosis Effect of Dehydroandrographolide Succinate: and Studies

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2022 Jan 11

PMID 35014931

Authors

Bowen Yin

Shuhua Zhang

Yuxi Huang

Yuanzhu Long

Yiguo Chen

Shiyun Zhao

Aiqun Zhou

Minghua Cao

Xiaoming Yin

Daya Luo

Affiliations

Soon will be listed here.

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 B (TXB) and 6-keto-prostaglandin F (6-keto-PGF). 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 = 386.9 mg/kg) by decreasing TXB 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%) ( < 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) ( < 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%) ( < 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.

References

Yusuf S, Zhao F, Mehta S, Chrolavicius S, Tognoni G, Fox K . Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001; 345(7):494-502. DOI: 10.1056/NEJMoa010746. View

Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J . Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018; 379(16):1529-1539. DOI: 10.1056/NEJMoa1804988. View

Bates E, Lau W, Angiolillo D . Clopidogrel-drug interactions. J Am Coll Cardiol. 2011; 57(11):1251-63. DOI: 10.1016/j.jacc.2010.11.024. View

Hossain S, Urbi Z, Karuniawati H, Mohiuddin R, Moh Qrimida A, Allzrag A . (Burm. f.) Wall. ex Nees: An Updated Review of Phytochemistry, Antimicrobial Pharmacology, and Clinical Safety and Efficacy. Life (Basel). 2021; 11(4). PMC: 8072717. DOI: 10.3390/life11040348. View

Yan L, Ruan J, Zhang L, Fan F, Zhang F, Wang A . Effect of aqueous extracts of several kinds of herbs on human platelet aggregation and expression of P-selectin in vitro. Chin J Integr Med. 2014; 21(4):286-90. DOI: 10.1007/s11655-013-1540-5. View

Kumar S, Singh B, Bajpai V . Andrographis paniculata (Burm.f.) Nees: Traditional uses, phytochemistry, pharmacological properties and quality control/quality assurance. J Ethnopharmacol. 2021; 275:114054. DOI: 10.1016/j.jep.2021.114054. View

Gupta S, Mishra K, Kumar B, Singh S, Ganju L . Andrographolide attenuates complete freund's adjuvant induced arthritis via suppression of inflammatory mediators and pro-inflammatory cytokines. J Ethnopharmacol. 2020; 261:113022. DOI: 10.1016/j.jep.2020.113022. View

Gaziano J, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick P . Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet. 2018; 392(10152):1036-1046. PMC: 7255888. DOI: 10.1016/S0140-6736(18)31924-X. View

Lee M, Ovbiagele B . Vascular events after stroke: terutroban fails to PERFORM. Lancet. 2011; 377(9782):1980-2. DOI: 10.1016/S0140-6736(11)60708-3. View

10.

Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H . Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine. 1999; 6(1):27-31. DOI: 10.1016/S0944-7113(99)80031-2. View

11.

Lu W, Lin K, Hsu M, Chou D, Hsiao G, Sheu J . Suppression of NF-κB signaling by andrographolide with a novel mechanism in human platelets: regulatory roles of the p38 MAPK-hydroxyl radical-ERK2 cascade. Biochem Pharmacol. 2012; 84(7):914-24. DOI: 10.1016/j.bcp.2012.06.030. View

12.

Yuhki K, Kojima F, Kashiwagi H, Kawabe J, Fujino T, Narumiya S . Roles of prostanoids in the pathogenesis of cardiovascular diseases: Novel insights from knockout mouse studies. Pharmacol Ther. 2010; 129(2):195-205. DOI: 10.1016/j.pharmthera.2010.09.004. View

13.

Sareer O, Ahmad S, Umar S . Andrographis paniculata: a critical appraisal of extraction, isolation and quantification of andrographolide and other active constituents. Nat Prod Res. 2014; 28(23):2081-101. DOI: 10.1080/14786419.2014.924004. View

14.

Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J . Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. Eur J Pharmacol. 2006; 553(1-3):39-45. DOI: 10.1016/j.ejphar.2006.09.052. View

15.

Mauricio A, Rosa M, Cantadori L, Pereira C, de Souza Goncalves R, Resende L . Bone marrow toxicity induced by clopidogrel. Int J Cardiol. 2014; 174(3):e112-3. DOI: 10.1016/j.ijcard.2014.04.194. View

16.

Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S . Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med. 2007; 73(6):503-11. DOI: 10.1055/s-2007-967181. View

17.

Bye A, Unsworth A, Gibbins J . Platelet signaling: a complex interplay between inhibitory and activatory networks. J Thromb Haemost. 2016; 14(5):918-30. PMC: 4879507. DOI: 10.1111/jth.13302. View

18.

Sirikarin T, Palo T, Chotewuttakorn S, Chandranipapongse W, Limsuvan S, Akarasereenont P . The Effects of on Platelet Activity in Healthy Thai Volunteers. Evid Based Complement Alternat Med. 2018; 2018:2458281. PMC: 6106912. DOI: 10.1155/2018/2458281. View

19.

Kij A, Mateuszuk L, Sitek B, Przyborowski K, Zakrzewska A, Wandzel K . Simultaneous quantification of PGI2 and TXA2 metabolites in plasma and urine in NO-deficient mice by a novel UHPLC/MS/MS method. J Pharm Biomed Anal. 2016; 129:148-154. DOI: 10.1016/j.jpba.2016.06.050. View

20.

Majumdar M, Misra T, Roy D . In vitro anti-biofilm activity of 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata against Pseudomonas aeruginosa. Braz J Microbiol. 2019; 51(1):15-27. PMC: 7058757. DOI: 10.1007/s42770-019-00169-0. View