Danhong Huayu Koufuye prevents venous thrombosis through antiinflammation via Sirtuin 1/NF-κB signaling pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Danhong Huayu Koufuye (DHK), a compound traditional Chinese medicine, is composed of Salvia miltiorrhiza radix (Salvia miltiorrhiza Bge.), Angelicae Sinensis radix (Angelicae Sinensis (Oliv.) Diels.), Chuanxiong rhizoma (Ligusticum chuanxiong Hort.), Persicae semen (Prunus persica (L.) Batsch), Carthami flos (Carthamus tinctorius L.), Bupleuri radix (Bupleurum chinense DC.) and Aurantii fructus (Citrus aurantium L.). DHK prevents deep vein thrombosis (DVT) through antiinflammation. However, the antiinflammatory mechanism of DHK is still unknown.

OBJECTIVE:

The aim of this study was to evaluate whether DHK prevented venous thrombosis through antiinflammation via Sirtuin 1 (SIRT1)/NF-κB signaling pathway.

METHODS:

Inferior vena cava (IVC) stenosis-induced DVT rat model was established. Rats were administered with DHK (1.6, 3.2 or 6.4 mL/kg/d, p.o.), heparin (200 U/kg/d, i.v.), clopidogrel (25 mg/kg/d, p.o.), resveratrol (50 mg/kg/d, p.o.) or vehicle (p.o.) once daily for two days. Blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts and platelet activity were evaluated. Serum levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay. Pathological changes were observed by hematoxylin-eosin (HE) staining. Protein expressions in thrombosed IVCs were evaluated by Western blot and/or immunofluorescence analyses. SIRT1 mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Besides, SIRT1-specific inhibitor EX527 was pretreated to confirm the role of SIRT1/NF-κB signaling pathway in the antithrombotic effect of DHK.

RESULTS:

DHK remarkably prevented DVT. DHK had no effects on blood coagulation, blood fibrinolysis, blood viscosity, blood cell counts or platelet activity. But DHK significantly up-regulated protein and mRNA expressions of SIRT1, and reduced leukocytes infiltration into thrombus and vein wall, serum levels of inflammatory cytokines, and protein expressions of acetylated p65 (Ace-p65), phosphorylated p65 (p-p65) and tissue factor (TF). Moreover, the antithrombotic effect of DHK was significantly abolished by EX527.

CONCLUSION:

DHK may prevent DVT by inhibiting inflammation via SIRT1/NF-κB signaling pathway.

• Authors: Han Liu, Peng Li, Juan Lin, Wenpei Chen, Haibiao Guo, Jianyun Lin, Jin Liu, Ziqi Lu, Xiaolan Yao, Yang Chen, Baoqin Lin
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 241 Pg. 111975 (Sep 15 2019) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 31141719 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Drugs, Chinese Herbal
• Fibrinolytic Agents
• IL1B protein, rat
• Interleukin-1beta
• Phytochemicals
• Tumor Necrosis Factor-alpha
• danhong huayu koufuye
• Sirt1 protein, rat
• Sirtuin 1

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology, therapeutic use)
• Blood Cell Count
• Blood Coagulation (drug effects)
• Drugs, Chinese Herbal (chemistry, pharmacology, therapeutic use)
• Female
• Fibrinolytic Agents (chemistry, pharmacology, therapeutic use)
• Interleukin-1beta (blood)
• Male
• Phytochemicals (analysis, pharmacology, therapeutic use)
• Platelet Activation (drug effects)
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• Sirtuin 1 (genetics, metabolism)
• Tumor Necrosis Factor-alpha (blood)
• Venous Thrombosis (blood, drug therapy, genetics, metabolism)